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Standards o* edical Care in Diabetesd()%!

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ERICA$ DIABETES ASSOCIATIO$

iabetes +ellitus is a c,ronic illness t,at re-uires continuing +edical care and ongoing .atient sel*/ +anage+ent education and su..ort to .re0ent acute co+.lications and to reduce t,e ris1 o* long/ter+ co+.lications. Diabetes care is co+.le2 and re-uires +ulti*actorial ris1 reduction strategies be3ond gl3ce+ic con/ trol. A large bod3 o* e0idence e2ists t,at su..orts a range o* inter0entions to i+.ro0e diabetes outco+es. T,ese standards o* care are intended to .ro0ide clinicians, .atients, researc,ers, .a3ers, and ot,er interested indi0iduals 4it, t,e co+.onents o* diabetes care, general treat+ent goals, and tools to e0al/ uate t,e -ualit3 o* care. Alt,oug, indi0id/ ual .re*erences, co+orbidities, and ot,er .atient *actors +a3 re-uire +odi5cation o* goals, targets t,at are desirable *or +ost .atients 4it, diabetes are .ro0ided. S.e/ ci5call3 titled sections o* t,e standards address c,ildren 4it, diabetes, .regnant 4o+en, and .eo.le 4it, .rediabetes. T,ese standards are not intended to .re/ clude clinical judg+ent or +ore e2tensi0e e0aluation and +anage+ent o* t,e .atient b3 ot,er s.ecialists as needed. 6or +ore detailed in*or+ation about +anage+ent o* diabetes, re*er to re*erences 7%8!9. T,e reco++endations included are screening, diagnostic, and t,era.eutic actions t,at are 1no4n or belie0ed to *a0orabl3 a**ect ,ealt, outco+es o* .atients 4it, diabetes. A large nu+ber o* t,ese inter0entions ,a0e been s,o4n to be cost/ e**ecti0e 7:9. A grading s3ste+ 7Table %9, de0elo.ed b3 t,e A+erican Diabetes Asso/ ciation 7ADA9 and +odeled a*ter e2isting +et,ods, 4as utili;ed to clari*3 and codi*3 t,e e0idence t,at *or+s t,e basis *or t,e reco++endations. T,e le0el o* e0idence t,at su..orts eac, reco++endation is listed a*ter eac, reco++endation using t,e letters A, B, C, or E. care.diabetesjournals.org

T,ese standards o* care are re0ised annuall3 b3 t,e ADA<s +ultidisci.linar3 #ro*essional #ractice Co++ittee, incor/ .orating ne4 e0idence. 6or t,e current re0ision, co++ittee +e+bers s3ste+ati/ call3 searc,ed edline *or ,u+an stud/ ies related to eac, subsection and .ublis,ed since % &anuar3 ()%%. Reco+/ +endations 7bulleted at t,e beginning o* eac, subsection and also listed in t,e =E2ecuti0e Su++ar3> Standards o* edical Care in Diabetesd()%!?9 4ere re0ised based on ne4 e0idence or, in so+e cases, to clari*3 t,e .rior reco+/ +endation or +atc, t,e strengt, o* t,e 4ording to t,e strengt, o* t,e e0idence. A table lin1ing t,e c,anges in reco+/ +endations to ne4 e0idence can be re/ 0ie4ed at ,tt.>@@.r o *es s ional.diabete s. org@C#R. As is t,e case *or all .osition state+ents, t,ese standards o* care 4ere re0ie4ed and a..ro0ed b3 t,e E2ecuti0e Co++ittee o* ADA<s Board o* Directors, 4,ic, includes ,ealt, care .ro*essionals, scientists, and la3 .eo.le. 6eedbac1 *ro+ t,e larger clinical co++unit3 4as 0aluable *or t,e ()%! re0ision o* t,e standards. Readers 4,o 4is, to co++ent on t,e =Standards o* edical Care in Diabetesd()%!? are in0ited to do so at , tt .> @ @ .r o *e ss i o na l . diabetes.org@C#R. e+bers o* t,e #ro*essional #ractice Co++ittee disclose all .otential 5nan/ cial conAicts o* interest 4it, industr3. T,ese disclosures 4ere discussed at t,e onset o* t,e standards re0ision +eeting. e+bers o* t,e co++ittee, t,eir e+/ .lo3er, and t,eir disclosed conAicts o* interest are listed in t,e =#ro*essional #ractice Co++ittee *or t,e ()%! Clinical #ractice Reco++endations? table 7see .. S%)B9. T,e ADA *unds de0elo.+ent o* t,e standards and all its .osition state/ +ents out o* its general re0enues and

does not use industr3 su..ort *or t,ese .ur.oses. I. CLASSI6ICATIO$ A$D DIAC$OSIS A. Classi5cation T,e classi5cation o* diabetes includes *our clinical classes>
c

T3.e % diabetes 7results *ro+ b/cell destruction, usuall3 leading to absolute insulin de5cienc39 T3.e ( diabetes 7results *ro+ a .ro/ gressi0e insulin secretor3 de*ect on t,e bac1ground o* insulin resistance9 Ot,er s.eci5c t3.es o* diabetes due to ot,er causes, e.g., genetic de*ects in b/cell *unction, genetic de*ects in in/ sulin action, diseases o* t,e e2ocrine .ancreas 7suc, as c3stic 5brosis9, and drug/ or c,e+ical/induced 7suc, as in t,e treat+ent o* DIV@AIDS or a*ter or/ gan trans.lantation9 Cestational diabetes +ellitus 7CD 9 7diabetes diagnosed during .regnanc3 t,at is not clearl3 o0ert diabetes9

So+e .atients cannot be clearl3 clas/ si5ed as t3.e % or t3.e ( diabetic. Clinical .resentation and disease .rogression 0ar3 considerabl3 in bot, t3.es o* diabetes. Occasionall3, .atients 4,o ot,er4ise ,a0e t3.e ( diabetes +a3 .resent 4it, 1etoacidosis. Si+ilarl3, .atients 4it, t3.e % diabetes +a3 ,a0e a late onset and slo4 7but relentless9 .rogression o* disease des.ite ,a0ing *eatures o* autoi++une disease. Suc, di*5culties in diagnosis +a3 occur in c,ildren, adolescents, and adults. T,e true diagnosis +a3 beco+e +ore ob0ious o0er ti+e. B. Diagnosis o* diabetes 6or decades, t,e diagnosis o* diabetes 4as based on .las+a glucose criteria, eit,er t,e *asting .las+a glucose 76#C9 or t,e

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Originall3 a..ro0ed %BEE. ost recent re0ie4@re0ision October ()%(. #osition State+ent DOI> %).(!!F@dc%!/S)%% G ()%! b3 t,e A+erican Diabetes Association. Readers +a3 use t,is article as long as t,e 4or1 is .ro.erl3 cited, t,e use is educational and not *or .ro5t, and t,e 4or1 is not altered. See ,tt.>@@creati0eco++ons.org@ licenses@b3/nc/nd@!.)@ *or details.

(/, 0alue in t,e FH/g oral glucose toler/ ance test 7OCTT9 7H9. In ())B, an International E2.ert Co++ittee t,at included re.resentati0es o* t,e ADA, t,e International Diabetes

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Table %dADA e0idence grading s3ste+ *or clinical .ractice reco++endations Le0el o* e0idence A

Descri.tion Clear e0idence *ro+ 4ell/conducted, generali;able RCTs t,at are ade-uatel3 .o4ered, including> c E0idence *ro+ a 4ell/conducted +ulticenter trial c E0idence *ro+ a +eta/anal3sis t,at incor.orated -ualit3 ratings in t,e anal3sis Co+.elling none2.eri+ental e0idence, i.e., =all or none? rule de0elo.ed b3 t,e Centre *or E0idence/Based edicine at t,e Uni0ersit3 o* O2*ord Su..orti0e e0idence *ro+ 4ell/conducted RCTs t,at are ade-uatel3 .o4ered, including> c E0idence *ro+ a 4ell/conducted trial at one or +ore institutions c E0idence *ro+ a +eta/anal3sis t,at incor.orated -ualit3 ratings in t,e anal3sis Su..orti0e e0idence *ro+ 4ell/conducted co,ort studies c E0idence *ro+ a 4ell/conducted .ros.ecti0e co,ort stud3 or registr3 c E0idence *ro+ a 4ell/conducted +eta/anal3sis o* co,ort studies Su..orti0e e0idence *ro+ a 4ell/conducted case/control stud3 Su..orti0e e0idence *ro+ .oorl3 controlled or uncontrolled studies c E0idence *ro+ rando+i;ed clinical trials 4it, one or +ore +ajor or t,ree or +ore +inor +et,odological Aa4s t,at could in0alidate t,e results c E0idence *ro+ obser0ational studies 4it, ,ig, .otential *or bias 7suc, as case series 4it, co+.arison 4it, ,istorical controls9 c E0idence *ro+ case series or case re.orts ConAicting e0idence 4it, t,e 4eig,t o* e0idence su..orting t,e reco++endation E2.ert consensus or clinical e2.erience

6ederation 7ID69, and t,e Euro.ean Association *or t,e Stud3 o* Diabetes 7EASD9 reco++ended t,e use o* t,e A%C test to diagnose diabetes, 4it, a t,res,old o* J".HI 7"9, and t,e ADA ado.ted t,is criterion in ()%) 7H9. T,e diagnostic test s,ould be .er*or+ed using a +et,od t,at is certi5ed b3 t,e $CS# and standardi;ed or traceable to t,e Diabetes Control and Co+.lications Trial 7DCCT9 re*erence as/ sa3. Alt,oug, .oint/o*/care 7#OC9 A%C as/ sa3s +a3 be $CS# certi5ed, .ro5cienc3 testing is not +andated *or .er*or+ing t,e test, so use o* t,ese assa3s *or diagnostic .ur.oses could be .roble+atic. E.ide+iological datasets s,o4 a si+/ ilar relations,i. *or A%C to t,e ris1 o* retino.at,3 as ,as been s,o4n *or t,e corres.onding 6#C and (/, #C t,res,/ olds. T,e A%C ,as se0eral ad0antages to t,e 6#C and OCTT, including greater con0enience 7since *asting is not re-uired9, e0idence to suggest greater .reanal3tical stabilit3, and less da3/to/da3 .erturbations during .eriods o* stress and illness. T,ese ad0antages +ust be balanced b3 greater cost, t,e li+ited a0ailabilit3 o*

A%C testing in certain regions o* t,e de0elo.ing 4orld, and t,e inco+.lete correlation bet4een A%C and a0erage glucose in certain indi/ 0iduals. In addition, DbA%c le0els +a3 0ar3 4it, .atients< race@et,nicit3 7F,E9. So+e

#C9 re+ain 0alid as 4ell 7Table (9. &ust as t,ere is less t,an %))I concordance be/ t4een t,e 6#C and (/, #C tests, t,ere is no .er*ect concordance bet4een A%C and eit,er glucose/based test. Anal3ses o* t,e $ational Dealt, and $utrition E2a+ina/ tion Sur0e3 7$DA$ES9 data indicate t,at, assu+ing uni0ersal screening o* t,e un/ diagnosed, t,e A%C cut .oint o* J".HI identi5es one/t,ird *e4er cases o* undiag/ nosed diabetes t,an a *asting glucose cut .oint o* J%(" +g@dL 7F.) ++ol@L9 7%%9, and nu+erous studies ,a0e con5r+ed t,at at t,ese cut .oints t,e (/, OCTT 0alue diagnoses +ore screened .eo.le 4it, diabetes 7%(9. Do4e0er, in .ractice, a large .ortion o* t,e diabetic .o.ulation re/ +ains una4are o* its condition. T,us, t,e lo4er sensiti0it3 o* A%C at t,e designated cut .oint +a3 4ell be o**set b3 t,e test<s greater .racticalit3, and 4ider a..lication o* a +ore con0enient test 7A%C9 +a3 actu/ all3 increase t,e nu+ber o* diagnoses +ade. As 4it, +ost diagnostic tests, a test result diagnostic o* diabetes s,ould be re.eated to rule out laborator3 error, unless t,e diagnosis is clear on clinical grounds, suc, as a .atient 4it, a ,3.er/ gl3ce+ic crisis or classic s3+.to+s o* ,3.ergl3ce+ia and a rando+ .las+a ,a0e .osited t,at gl3cation rates di**er b3 race 74it,, *or e2a+.le, A*rican A+ericans ,a0ing ,ig,er rates o* gl3cation9, but t,is is contro0ersial. A recent e.ide+iological stud3 *ound t,at, 4,en +atc,ed *or 6#C, A*rican A+ericans 74it, and 4it,out dia/ betes9 indeed ,ad ,ig,er A%C t,an 4,ites, but also ,ad ,ig,er le0els o* *ructosa+ine and gl3cated albu+in and lo4er le0els o* %,H an,3droglucitol, suggesting t,at t,eir gl3ce+ic burden 7.articularl3 .ost.ran/ diall39 +a3 be ,ig,er 7B9. E.ide+iological studies *or+ing t,e *ra+e4or1 *or reco+/ +ending use o* t,e A%C to diagnose diabe/ tes ,a0e all been in adult .o.ulations. K,et,er t,e cut .oint 4ould be t,e sa+e to diagnose c,ildren or adolescents 4it, t3.e ( diabetes is an area o* uncertaint3 7!,%)9. A%C inaccuratel3 reAects gl3ce+ia 4it, certain ane+ias and ,e+oglobino.a/ t,ies. 6or .atients 4it, an abnor+al ,e+o/ globin but nor+al red cell turno0er, suc, as sic1le cell trait, an A%C assa3 4it,out inter/ *erence *ro+ abnor+al ,e+oglobins s,ould be used 7an u.dated list is a0ailable at 444. ngs..org@inter*.as.9. 6or conditions 4it, abnor+al red cell turno0er, suc, as .reg/ nanc3, recent blood loss or trans*usion, or so+e ane+ias, t,e diagnosis o* diabetes +ust e+.lo3 glucose criteria e2clusi0el3. T,e establis,ed glucose criteria *or t,e diagnosis o* diabetes 76#C and (/,

glucose J()) +g@dL. It is .re*erable t,at t,e sa+e test be re.eated *or con5r/ +ation, since t,ere 4ill be a greater li1eli/ ,ood o* concurrence in t,is case. 6or e2a+.le, i* t,e A%C is F.)I and a re.eat result is ".EI, t,e diagnosis o* diabetes is con5r+ed. Do4e0er, i* t4o di**erent tests 7suc, as A%C and 6#C9 are bot, abo0e t,e diagnostic t,res,olds, t,e diagnosis o* di/ abetes is also con5r+ed. On t,e ot,er ,and, i* t4o di**erent tests are a0ailable in an indi0idual and t,e results are discordant, t,e test 4,ose result is abo0e t,e diagnostic cut .oint s,ould be re.eated, and t,e diagnosis is +ade based on t,e con5r+ed test. T,at is, i* a .atient +eets t,e diabetes criterion o* t,e A%C 7t4o results J".HI9 but not t,e 6#C 7,%(" +g@ dL or F.) ++ol@L9, or 0ice 0ersa, t,at .er/ son s,ould be considered to ,a0e diabetes. Since t,ere is .reanal3tical and ana/ l3tical 0ariabilit3 o* all t,e tests, it is also .ossible t,at 4,en a test 4,ose result 4as abo0e t,e diagnostic t,res,old is re/ .eated, t,e second 0alue 4ill be belo4 t,e diagnostic cut .oint. T,is is least li1el3 *or A%C, so+e4,at +ore li1el3 *or 6#C, and +ost li1el3 *or t,e (/, #C. Barring a laborator3 error, suc, .atients are li1el3 to ,a0e test results near t,e +argins o* t,e t,res,old *or a diagnosis. T,e ,ealt, care .ro*essional +ig,t o.t to

#osition State+ent *ollo4 t,e .atient closel3 and re.eat t,e testing in !8" +ont,s. T,e current diagnostic criteria *or diabetes are su++ari;ed in Table (. C. Categories o* increased ris1 *or diabetes 7.rediabetes9 In %BBF and ())!, t,e E2.ert Co++ittee on Diagnosis and Classi5cation o* Diabe/ tes ellitus 7%!,%:9 recogni;ed an inter/ +ediate grou. o* indi0iduals 4,ose glucose le0els, alt,oug, not +eeting cri/ teria *or diabetes, are ne0ert,eless too ,ig, to be considered nor+al. T,ese .er/ sons 4ere de5ned as ,a0ing i+.aired *ast/ ing glucose 7I6C9 76#C le0els %)) +g@dL LH." ++ol@LM to %(H +g@dL L".B ++ol@LM9 or i+.aired glucose tolerance 7ICT9 7(/, 0alues in t,e OCTT o* %:) +g@dL LF.E ++ol@LM to %BB +g@dL L%%.) ++ol@LM9. It s,ould be noted t,at t,e Korld Dealt, Organi;ation 7KDO9 and a nu+ber o* ot,er diabetes organi;ations de5ne t,e cut/ o** *or I6C at %%) +g@dL 7".% ++ol@L9. Indi0iduals 4it, I6C and@or ICT ,a0e been re*erred to as ,a0ing .rediabetes, indicating t,e relati0el3 ,ig, ris1 *or t,e *uture de0elo.+ent o* diabetes. I6C and ICT s,ould not be 0ie4ed as clinical entities in t,eir o4n rig,t but rat,er ris1 *actors *or diabetes as 4ell as cardio0ascular disease 7CVD9. I6C and ICT are associated 4it, obesit3 7es.eciall3 abdo+inal or 0is/ ceral obesit39, d3sli.ide+ia 4it, ,ig, tri/ gl3cerides and@or lo4 DDL c,olesterol, and ,3.ertension. As is t,e case 4it, t,e glucose +ea/ sures, se0eral .ros.ecti0e studies t,at
Table (dCriteria *or t,e diagnosis o* diabetes A%C J".HI. T,e test s,ould be .er*or+ed in a laborator3 using a +et,od t,at is $CS# certi5ed and standardi;ed to t,e DCCT assa3.N OR 6#C J%(" +g@dL 7F.) ++ol@L9. 6asting is de5ned as no caloric inta1e *or at least E ,.N OR (/, .las+a glucose J()) +g@dL 7%%.% ++ol@L9 during an OCTT. T,e test s,ould be .er*or+ed as described b3 t,e KDO, using a glucose load containing t,e e-ui0alent o* FH g an,3drous glucose dissol0ed in 4ater.N OR In a .atient 4it, classic s3+.to+s o* ,3.ergl3ce+ia or ,3.ergl3ce+ic crisis, a rando+ .las+a glucose J()) +g@dL 7% %. % + +o l@ L 9.
NIn t,e absence o* une-ui0ocal ,3.ergl3ce+ia, re/ sult s,ould be con5r+ed b3 re.eat testing.

used A%C to .redict t,e .rogression to diabetes de+onstrated a strong, continu/ ous association bet4een A%C and sub/ se-uent diabetes. In a s3ste+atic re0ie4 o* ::,()! indi0iduals *ro+ %" co,ort stud/ ies 4it, a *ollo4/u. inter0al a0eraging H." 3ears 7range (.E8%( 3ears9, t,ose 4it, an A%C bet4een H.H and ".)I ,ad a substan/ tiall3 increased ris1 o* diabetes 4it, H/3ear incidences ranging *ro+ B to (HI. An A%C range o* ".)8".HI ,ad a H/3ear ris1 o* de/ 0elo.ing diabetes bet4een (H to H)I and relati0e ris1 7RR9 () ti+es ,ig,er co+.ared 4it, an A%C o* H.)I 7%H9. In a co++unit3/ based stud3 o* blac1 and 4,ite adults 4it,out diabetes, baseline A%C 4as a stronger .redictor o* subse-uent diabetes and cardio0ascular e0ents t,an 4as *ast/ ing glucose 7%"9. Ot,er anal3ses suggest t,at an A%C o* H.FI is associated 4it, diabetes ris1 si+ilar to t,at in t,e ,ig,/ ris1 .artici.ants in t,e Diabetes #re0ention #rogra+ 7D##9 7%F9. Dence, it is reasonable to consider an A%C range o* H.F8".:I as identi*3ing in/ di0iduals 4it, .rediabetes. As is t,e case *or indi0iduals *ound to ,a0e I6C and ICT, indi0iduals 4it, an A%C o* H.F8".:I s,ould be in*or+ed o* t,eir increased ris1 *or diabetes as 4ell as CVD and counseled about e**ecti0e strategies to lo4er t,eir ris1s 7see Section IV9. As 4it, glucose +easure/ +ents, t,e continuu+ o* ris1 is cur0ilinear, so t,at as A%C rises, t,e ris1 o* diabetes rises dis.ro.ortionatel3 7%H9. Accordingl3, inter/ 0entions s,ould be +ost intensi0e and *ollo4/u. .articularl3 0igilant *or t,ose 4it, A%Cs abo0e ".)I, 4,o s,ould be con/ sidered to be at 0er3 ,ig, ris1. Table ! su++ari;es t,e categories o* .rediabetes. II. TESTI$C 6OR DIABETES I$ AS' #TO ATIC #ATIE$TS Reco++endations c Testing to detect t3.e ( diabetes and .rediabetes in as3+.to+atic .eo.le s,ould be considered in adults o* an3 age 4,o are o0er4eig,t or obese 7B I ( J(H 1g@+ 9 and 4,o ,a0e one or +ore additional ris1 *actors *or diabetes 7Table :9. In t,ose 4it,out t,ese ris1 *actors, testing s,ould begin at age :H. 7B9 c I* tests are nor+al, re.eat testing at least at !/3ear inter0als is reasonable. 7E9 c To test *or diabetes or .rediabetes, t,e A%C, 6#C, or FH/g (/, OCTT are a..ro/ .riate. 7B9 c In t,ose identi5ed 4it, .rediabetes, identi*3 and, i* a..ro.riate, treat ot,er CVD ris1 *actors. 7B9

Table !dCategories o* increased ris1 *or diabetes 7.rediabetes9N 6#C %)) +g@dL 7H." ++ol@L9 to %(H +g@dL 7".B ++ol@L9 7I6C9 OR (/, .las+a glucose in t,e FH/g OCTT %:) +g@dL 7F.E ++ol@L9 to %BB +g@dL 7%%.) ++ol@L9 7ICT9 OR A%C H.F8".:I
N6or all t,ree tests, ris1 is continuous, e2tending be/ lo4 t,e lo4er li+it o* t,e range and beco+ing dis/ .ro.ortionatel3 greater at ,ig,er ends o* t,e range.

#osition State+ent

unli1el3 to occur. In a large rando+i;ed controlled trial 7RCT9 in Euro.e, general .ractice .atients bet4een t,e ages o* :)8 "B 3ears 4ere screened *or diabetes and

6or +an3 illnesses, t,ere is a +ajor dis/ tinction bet4een screening and diagnostic testing. Do4e0er, *or diabetes, t,e sa+e tests 4ould be used *or =screening? as *or diagnosis. Diabetes +a3 be identi5ed an3/ 4,ere along a s.ectru+ o* clinical scenar/ ios ranging *ro+ a see+ingl3 lo4/ris1 indi0idual 4,o ,a..ens to ,a0e glucose testing, to a ,ig,er/ris1 indi0idual 4,o+ t,e .ro0ider tests because o* ,ig, sus.icion o* diabetes, to t,e s3+.to+atic .atient. T,e discussion ,erein is .ri+aril3 *ra+ed as testing *or diabetes in t,ose 4it,out s3+.to+s. T,e sa+e assa3s used *or test/ ing *or diabetes 4ill also detect indi0iduals 4it, .rediabetes. A. Testing *or t3.e ( diabetes and ris1 o* *uture diabetes in adults #rediabetes and diabetes +eet establis,ed criteria *or conditions in 4,ic, earl3 de/ tection is a..ro.riate. Bot, conditions are co++on, increasing in .re0alence, and i+.ose signi5cant .ublic ,ealt, burdens. T,ere is a long .res3+.to+atic .,ase be*ore t,e diagnosis o* t3.e ( diabetes is usuall3 +ade. Relati0el3 si+.le tests are a0ailable to detect .reclinical disease. Ad/ ditionall3, t,e duration o* gl3ce+ic burden is a strong .redictor o* ad0erse outco+es, and e**ecti0e inter0entions e2ist to .re0ent .rogression o* .rediabetes to diabetes 7see Section IV9 and to reduce ris1 o* co+.li/ cations o* diabetes 7see Section VI9. T3.e ( diabetes is *re-uentl3 not di/ agnosed until co+.lications a..ear, and a..ro2i+atel3 one/*ourt, o* all .eo.le 4it, diabetes in t,e U.S. +a3 be undiag/ nosed. T,e e**ecti0eness o* earl3 identi5ca/ tion o* .rediabetes and diabetes t,roug, +ass testing o* as3+.to+atic indi0iduals ,as not been .ro0en de5niti0el3, and rigorous trials to .ro0ide suc, .roo* are

t,en rando+l3 assigned b3 .ractice to routine care o* diabetes or intensi0e treat/ +ent o* +ulti.le ris1 *actors. A*ter H.! 3ears o* *ollo4/u., CVD ris1 *actors 4ere +odestl3 but signi5cantl3 +ore i+.ro0ed 4it, intensi0e treat+ent. Incidence o* 5rst CVD e0ent and +ortalit3 rates 4ere not signi5cantl3 di**erent bet4een grou.s 7%E9. T,is stud3 4ould see+ to add su./ .ort *or earl3 treat+ent o* screen/detected diabetes, as ris1 *actor control 4as e2cel/ lent e0en in t,e routine treat+ent ar+ and bot, grou.s ,ad lo4er e0ent rates t,an .redicted. T,e absence o* a control unscreened ar+ li+its t,e abilit3 to de5/ nitel3 .ro0e t,at screening i+.acts out/ co+es. at,e+atical +odeling studies suggest t,at screening inde.endent o* ris1 *actors beginning at age !) 3ears or age :H 3ears is ,ig,l3 cost/e**ecti0e 7,J%%,))) .er -ualit3/adjusted li*e/ 3ear gained9 7%B9. Reco++endations *or testing *or di/ abetes in as3+.to+atic, undiagnosed adults are listed in Table :. Testing s,ould be considered in adults o* an3 age 4it, ( B I J(H 1g@+ and one or +ore o* t,e 1no4n ris1 *actors *or diabetes. In addi/ tion to t,e listed ris1 *actors, certain +ed/ ications, suc, as glucocorticoids and anti.s3c,otics 7()9, are 1no4n to in/ crease t,e ris1 o* t3.e ( diabetes. T,ere is co+.elling e0idence t,at lo4er B I cut .oints suggest diabetes ris1 in so+e racial and et,nic grou.s. In a large +ultiet,nic co,ort stud3, *or an e-ui0alent incidence rate o* diabetes ( con*erred b3 a B I o* !) 1g@+ in 4,ites, t,e B I cuto** 0alue 4as

(: 1g@+ in Sout, Asians, (H 1g@+ in ( C,inese, and (" 1g@+ in A*rican A+eri/ cans 7(%9. Dis.arities in screening rates, not e2.lainable b3 insurance status, are ,ig,lig,ted b3 e0idence t,at des.ite +uc, ,ig,er .re0alence o* t3.e ( diabe/ tes, non/Caucasians in an insured .o.u/ lation are no +ore li1el3 t,an Caucasians to be screened *or diabetes 7((9. Because age is a +ajor ris1 *actor *or diabetes, test/ ing o* t,ose 4it,out ot,er ris1 *actors s,ould begin no later t,an age :H 3ears. T,e A%C, 6#C, or t,e (/, OCTT are a..ro.riate *or testing. It s,ould be noted t,at t,e tests do not necessaril3 detect diabetes in t,e sa+e indi0iduals. T,e e*5cac3 o* inter0entions *or .ri+ar3 .re/ 0ention o* t3.e ( diabetes 7(!8(B9 ,as .ri+aril3 been de+onstrated a+ong in/ di0iduals 4it, ICT, not *or indi0iduals 4it, isolated I6C or *or indi0iduals 4it, s.eci5c A%C le0els. T,e a..ro.riate inter0al bet4een tests is not 1no4n 7!)9. T,e rationale *or t,e !/3ear inter0al is t,at *alse nega/ ti0es 4ill be re.eated be*ore substantial ti+e ela.ses, and t,ere is little li1eli,ood t,at an indi0idual 4ill de0elo. signi5cant co+.lications o* diabetes 4it,in ! 3ears o* a negati0e test result. In t,e +odeling stud3, re.eat screening e0er3 ! or H 3ears 4as cost/e**ecti0e 7%B9. Because o* t,e need *or *ollo4/u. and discussion o* abnor+al results, testing s,ould be carried out 4it,in t,e ,ealt, care setting. Co++unit3 screening outside a ,ealt, care setting is not reco++ended because .eo.le 4it, .ositi0e tests +a3 not

see1, or ,a0e access to, a..ro.riate *ollo4/ u. testing and care. Con0ersel3, t,ere +a3 be *ailure to ensure a..ro.riate re.eat testing *or indi0iduals 4,o test negati0e. Co++u/ nit3 screening +a3 also be .oorl3 targetedO i. e., it +a3 *ail to reac, t,e grou.s +ost at ris1 and ina..ro.riatel3 test t,ose at lo4 ris1 7t,e 4orried 4ell9 or e0en t,ose alread3 diag/ nosed. B. Screening *or t3.e ( diabetes in c,ildren Reco++endations c Testing to detect t3.e ( diabetes and .rediabetes s,ould be considered in c,il/ dren and adolescents 4,o are o0er4eig,t and 4,o ,a0e t4o or +ore additional ris1 *actors *or diabetes 7Table H9. 7E9 T,e incidence o* t3.e ( diabetes in adolescents ,as increased dra+aticall3 in t,e last decade, es.eciall3 in +inorit3 .o.ulations 7!%9, alt,oug, t,e disease re+ains rare in t,e general .ediatric .o./ ulation 7!(9. Consistent 4it, reco+/ +endations *or adults, c,ildren and 3out, at increased ris1 *or t,e .resence or t,e de0elo.+ent o* t3.e ( diabetes s,ould be tested 4it,in t,e ,ealt, care setting 7!!9. T,e reco++endations o* t,e ADA consensus state+ent =T3.e ( Diabetes in C,ildren and Adolescents,? 4it, so+e +odi5cations, are su++a/ ri;ed in Table H. C. Screening *or t3.e % diabetes Reco++endations c Consider re*erring relati0es o* t,ose
4it, .r e di a b ete s s ,o ul d b e te st e d 3 ea rl 39 a nd r is 1 s ta tu s .
NAt/ris1 B I +a3 be lo4er in so+e et,nic grou.s.

Table :dCriteria *or testing *or diabetes in as3+.to+atic adult indi0iduals %. Testing s,ould be considered in all adults 4,o are o0er4eig,t 7B I J(H 1g@+ N9 and ,a0e additional ris1 *actors> c .,3sical inacti0it3 c 5rst/degree relati0e 4it, diabetes c ,ig,/ris1 race@et,nicit3 7e.g., A*rican A+erican, Latino, $ati0e A+erican, Asian A+erican, #aci5c Islander9 c 4o+en 4,o deli0ered a bab3 4eig,ing .B lb or 4ere diagnosed 4it, CD c ,3.ertension 7J%:)@B) ++Dg or on t,era.3 *or ,3.ertension9 c DDL c,olesterol le0el ,!H +g@dL 7).B) ++ol@L9 and@or a trigl3ceride le0el .(H) +g@dL 7(.E( ++ol@L9 c 4o+en 4it, .ol3c3stic o0ar3 s3ndro+e c A%C JH.FI, ICT, or I6C on .re0ious testing c ot,er clinical conditions associated 4it, insulin resistance 7e.g., se0ere obesit3, acant,osis nigricans9 c ,istor3 o* CVD In t,e absence o* t,e abo0e criteria, testing *or diabetes s,ould begin at age :H I* results are nor+al, testing s,ould be re.eated at least at !/3ear inter0als, 4it, consideration o* +ore *re-uent testing de.ending on initial results 7e.g., t,ose
(

(. 3ears. !.

4it, t3.e % diabetes *or antibod3 test/ ing *or ris1 assess+ent in t,e setting o* a clinical researc, stud3. 7E9 Cenerall3, .eo.le 4it, t3.e % diabetes .resent 4it, acute s3+.to+s o* diabetes and +ar1edl3 ele0ated blood glucose le0els, and so+e cases are diagnosed 4it, li*e/t,reatening 1etoacidosis. E0idence *ro+ se0eral studies suggests t,at +ea/ sure+ent o* islet autoantibodies in rela/ ti0es o* t,ose 4it, t3.e % diabetes identi5es indi0iduals 4,o are at ris1 *or de0elo.ing t3.e % diabetes. Suc, testing, cou.led 4it, education about s3+.to+s o* diabetes and *ollo4/u. in an obser0a/ tional clinical stud3, +a3 allo4 earlier identi5cation o* onset o* t3.e % diabetes and lessen .resentation 4it, 1etoacidosis at ti+e o* diagnosis. T,is testing +a3 be a..ro.riate in t,ose 4,o ,a0e relati0es 4it, t3.e % diabetes, in t,e conte2t o*

Table HdTesting *or t3.e ( diabetes in as3+.to+atic c,ildrenN Criteria c O0er4eig,t 7B I .EHt, .ercentile *or age and se2, 4eig,t *or ,eig,t .EHt, .ercentile, or 4eig,t .%()I o* ideal *or ,eig,t9 #lus an3 t4o o* t,e *ollo4ing ris1 *actors> c 6a+il3 ,istor3 o* t3.e ( diabetes in 5rst/ or second/degree relati0e c Race@et,nicit3 7$ati0e A+erican, A*rican A+erican, Latino, Asian A+erican, #aci5c Islander9 c Signs o* insulin resistance or conditions associated 4it, insulin resistance 7acant,osis nigricans, ,3.ertension, d3sli.ide+ia, .ol3c3stic o0ar3 s3ndro+e, or s+all/*or/gestational/ age birt, 4eig,t9 aternal ,istor3 o* diabetes or CD during t,e c,ild<s gestation c Age o* initiation> age %) 3ears or at onset o* .ubert3, i* .ubert3 occurs at a 3ounger age 6re-uenc3> e0er3 ! 3ears
N#ersons aged %E 3ears and 3ounger.

clinical researc, studies 7see, *or e2a+.le, ,tt.>@@444.diabetestrialnet.org9. Do4e0er, 4ides.read clinical testing o* as3+.to+atic lo4/ris1 indi0iduals cannot currentl3 be reco++ended, as it 4ould identi*3 0er3 *e4 indi0iduals in t,e general .o.ulation 4,o are at ris1. Indi0iduals 4,o screen .ositi0e s,ould be counseled about t,eir ris1 o* de0elo.ing diabetes and s3+.to+s o* diabetes, *ollo4ed closel3 to .re0ent de/ 0elo.+ent o* diabetic 1etoacidosis, and in*or+ed about clinical trials. Clinical studies are being conducted to test 0arious +et,ods o* .re0enting t3.e % diabetes in t,ose 4it, e0idence o* autoi++unit3. So+e inter0entions ,a0e de+onstrated +odest e*5cac3 in slo4ing b/cell loss earl3 in t3.e % diabetes 7!:,!H9, and *urt,er re/ searc, is needed to deter+ine 4,et,er t,e3 +a3 be e**ecti0e in .re0enting t3.e % diabetes. III. DETECTIO$ A$D DIAC$OSIS O6 CD Reco++endations c Screen *or undiagnosed t3.e ( diabetes at t,e 5rst .renatal 0isit in t,ose 4it, ris1 *actors, using standard diagnostic criteria. 7B9 c In .regnant 4o+en not .re0iousl3 1no4n to ,a0e diabetes, screen *or

CD at (:8(E 4ee1s o* gestation, using a FH/g (/, OCTT and t,e di/ agnostic cut .oints in Table ". 7B9 Screen 4o+en 4it, CD *or .ersistent diabetes at "8%( 4ee1s .ost.artu+, using t,e OCTT and non.regnanc3 diagnostic criteria. 7E9 Ko+en 4it, a ,istor3 o* CD s,ould ,a0e li*elong screening *or t,e de/ 0elo.+ent o* diabetes or .rediabetes at least e0er3 ! 3ears. 7B9 Ko+en 4it, a ,istor3 o* CD *ound to ,a0e .rediabetes s,ould recei0e li*est3le inter0entions or +et*or+in to .re0ent diabetes. 7A9

6or +an3 3ears, CD 4as de5ned as an3 degree o* glucose intolerance 4it, onset or 5rst recognition during .reg/ nanc3 7%!9, 4,et,er or not t,e condition .ersisted a*ter .regnanc3, and not e2/ cluding t,e .ossibilit3 t,at unrecogni;ed glucose intolerance +a3 ,a0e antedated or begun conco+itantl3 4it, t,e .reg/ nanc3. T,is de5nition *acilitated a uni*or+ strateg3 *or detection and classi5cation o* CD , but its li+itations 4ere recogni;ed *or +an3 3ears. As t,e ongoing e.ide+ic o* obesit3 and diabetes ,as led to +ore t3.e ( diabetes in 4o+en o* c,ildbearing age, t,e nu+ber o* .regnant 4o+en 4it, undiagnosed t3.e ( diabetes ,as increased 7!"9. Because o* t,is, it is reasonable to

screen 4o+en 4it, ris1 *actors *or t3.e ( diabetes 7Table :9 *or diabetes at t,eir initial .renatal 0isit, using standard diag/ nostic criteria 7Table (9. Ko+en 4it, di/ abetes *ound at t,is 0isit s,ould recei0e a diagnosis o* o0ert, not gestational, diabetes. CD carries ris1s *or t,e +ot,er and neonate. T,e D3.ergl3ce+ia and Ad/ 0erse #regnanc3 Outco+e 7DA#O9 stud3 7!F9, a large/scale 7O(H,))) .regnant 4o+en9 +ultinational e.ide+iological stud3, de+onstrated t,at ris1 o* ad0erse +aternal, *etal, and neonatal outco+es continuousl3 increased as a *unction o* +aternal gl3ce+ia at (:8(E 4ee1s, e0en 4it,in ranges .re0iousl3 considered nor/ +al *or .regnanc3. 6or +ost co+.lica/ tions, t,ere 4as no t,res,old *or ris1. T,ese results ,a0e led to care*ul recon/ sideration o* t,e diagnostic criteria *or CD . A*ter deliberations in ())E8 ())B, t,e International Association o* Diabetes and #regnanc3 Stud3 Crou.s 7IAD#SC9, an international consensus grou. 4it, re.resentati0es *ro+ +ulti.le obstetrical and diabetes organi;ations, including ADA, de0elo.ed re0ised rec/ o++endations *or diagnosing CD . T,e grou. reco++ended t,at all 4o+en not 1no4n to ,a0e .rior diabetes undergo a FH/g OCTT at (:8(E 4ee1s o* gestation. Additionall3, t,e grou. de/ 0elo.ed diagnostic cut .oints *or t,e *ast/ ing, %/,, and (/, .las+a glucose +easure+ents t,at con0e3ed an odds ratio *or ad0erse outco+es o* at least %.FH co+.ared 4it, 4o+en 4it, t,e +ean glucose le0els in t,e DA#O stud3. Current screening and diagnostic strate/ gies, based on t,e IAD#SC state+ent 7!E9, are outlined in Table ". T,ese ne4 criteria 4ill signi5cantl3 increase t,e .re0alence o* CD , .ri+ar/ il3 because onl3 one abnor+al 0alue, not t4o, is su*5cient to +a1e t,e diagnosis. T,e ADA recogni;es t,e antici.ated sig/ ni5cant increase in t,e incidence o* CD diagnosed b3 t,ese criteria and is sensiti0e to concerns about t,e =+edicali;ation? o* .regnancies .re0iousl3 categori;ed as nor/ +al. T,ese diagnostic criteria c,anges are being +ade in t,e conte2t o* 4orriso+e 4orld4ide increases in obesit3 and diabe/ tes rates, 4it, t,e intent o* o.ti+i;ing ges/

Table "dScreening *or and diagnosis o* CD #er*or+ a FH/g OCTT, 4it, .las+a glucose +easure+ent *asting and at % and ( ,, at (:8(E 4ee1s o* gestation in 4o+en not .re0iousl3 diagnosed 4it, o0ert diabetes.

T,e OCTT s,ould be .er*or+ed in t,e +orning a*ter an o0ernig,t *ast o* at least E

,. T,e diagnosis o* CD is +ade 4,en an3 o* t,e *ollo4ing .las+a glucose 0alues are e2ceeded> c 6asting> JB( +g@dL 7H.% ++ol@L9 c % ,> J%E) +g@dL 7%).) ++ol@L9 c (,> J % H! + g @ dL 7E .H ++ ol @ L9

tational outco+es *or 4o+en and t,eir babies. Ad+ittedl3, t,ere are *e4 data *ro+ rando+i;ed clinical trials regarding t,er/ a.eutic inter0entions in 4o+en 4,o 4ill no4 be diagnosed 4it, CD based on onl3 one blood glucose 0alue abo0e t,e

s.eci5ed cut .oints 7in contrast to t,e older criteria t,at sti.ulated at least t4o abnor/ +al 0alues9. Do4e0er, t,ere is e+erging obser0ational and retros.ecti0e e0idence t,at 4o+en diagnosed 4it, t,e ne4 criteria 7e0en i* t,e3 4ould not ,a0e been diagnosed 4it, older criteria9 ,a0e increased rates o* .oor .regnanc3 out/ co+es si+ilar to t,ose o* 4o+en 4it, CD b3 .rior criteria 7!B,:)9. E2.ected bene5ts to t,ese .regnancies and o**s.ring are in*erred *ro+ inter0ention trials t,at *ocused on 4o+en 4it, +ore +ild ,3.er/ gl3ce+ia t,an identi5ed using older CD diagnostic criteria and t,at *ound +odest bene5ts 7:%,:(9. T,e *re-uenc3 o* *ollo4/ u. and blood glucose +onitoring *or t,ese 4o+en is not 3et clear, but li1el3 to be less intensi0e t,an *or 4o+en diagnosed b3 t,e older criteria. It is i+.ortant to note t,at E)8B)I o* 4o+en in bot, o* t,e +ild CD studies 74,ose glucose 0alues o0er/ la..ed 4it, t,e t,res,olds reco++ended ,erein9 could be +anaged 4it, li*est3le t,era.3 alone. T,e A+erican College o* Obstetri/ cians and C3necologists announced in ()%% t,at t,e3 continue to reco++end use o* .rior diagnostic criteria *or CD 7:!9. Se0eral ot,er countries ,a0e ado.ted t,e ne4 criteria, and a re.ort *ro+ t,e KDO on t,is to.ic is .ending at t,e ti+e o* .ublication o* t,ese stand/ ards. T,e $ational Institutes o* Dealt, is .lanning to ,old a consensus de0elo./ +ent con*erence on t,is to.ic in ()%!. Because so+e cases o* CD +a3 re.resent .re/e2isting undiagnosed t3.e ( diabetes, 4o+en 4it, a ,istor3 o* CD s,ould be screened *or diabetes "8%( 4ee1s .ost.artu+, using non.reg/ nant OCTT criteria. Because o* t,eir .re/ .artu+ treat+ent *or ,3.ergl3ce+ia, use o* t,e A%C *or diagnosis o* .ersistent di/ abetes at t,e .ost.artu+ 0isit is not rec/ o++ended 7::9. Ko+en 4it, a ,istor3 o* CD ,a0e a greatl3 increased subse/ -uent ris1 *or diabetes 7:H9 and s,ould be *ollo4ed u. 4it, subse-uent screen/ ing *or t,e de0elo.+ent o* diabetes or .rediabetes, as outlined in Section II. Li*est3le inter0entions or +et*or+in s,ould be o**ered to 4o+en 4it, a ,is/ tor3 o* CD 4,o de0elo. .rediabetes, as discussed in Section IV. In t,e .ro/ s.ecti0e $urses< Dealt, Stud3 II, ris1 o* subse-uent diabetes a*ter a ,istor3 o* CD 4as signi5cantl3 lo4er in 4o+en 4,o *ollo4ed ,ealt,3 eating .atterns. Adjusting *or B I +oderatel3, but not

co+.letel3, association 7:" 9.

attenuated

t,is IV. #REVE$TIO$@DELA' O6 T'#E ( DIABETES Reco++endations c #atients 4it, ICT 7A9, I6C 7E9, or an A%C o* H.F8".:I 7E9 s,ould be re*erred to an e**ecti0e ongoing su..ort .rogra+ tar/ geting 4eig,t loss o* FI o* bod3 4eig,t and increasing .,3sical acti0it3 to at least %H) +in@4ee1 o* +oderate acti0it3 suc, as 4al1ing. c 6ollo4/u. counseling a..ears to be i+.ortant *or success. 7B9 c Based on t,e cost/e**ecti0eness o* diabetes .re0ention, suc, .rogra+s s,ould be co0ered b3 t,ird/.art3 .a3ers. 7B9 c et*or+in t,era.3 *or .re0ention o* t3.e ( diabetes +a3 be considered in t,ose 4it, ICT 7A9, I6C 7E9, or an A%C o* H.F8".:I 7E9, es.eciall3 *or t,ose 4it, ( B I .!H 1g@+ , aged ,") 3ears, and 4o+en 4it, .rior CD . 7A9 c At least annual +onitoring *or t,e de/ 0elo.+ent o* diabetes in t,ose 4it, .rediabetes is suggested. 7E9 c Screening *or and treat+ent o* +odi5/ able ris1 *actors *or CVD is suggested. 7B9 RCTs ,a0e s,o4n t,at indi0iduals at ,ig, ris1 *or de0elo.ing t3.e ( diabetes 7t,ose 4it, I6C, ICT, or bot,9 can signi*/ icantl3 decrease t,e rate o* onset o* diabetes 4it, .articular inter0entions 7(!8(B9. T,ese include intensi0e li*est3le +odi5ca/ tion .rogra+s t,at ,a0e been s,o4n to be 0er3 e**ecti0e 7OHEI reduction a*ter ! 3ears9 and use o* t,e .,ar+acological agents +et*or+in, a/ glucosidase in,ibi/ tors, orlistat, and t,ia;olidinediones, eac, o* 4,ic, ,as been s,o4n to decrease inci/ dent diabetes to 0arious degrees. 6ollo4/u. o* all t,ree large studies o* li*est3le inter0en/ tion ,as s,o4n sustained reduction in t,e rate o* con0ersion to t3.e ( diabetes, 4it, :!I reduction at () 3ears in t,e Da Ping stud3 7:F9, :!I reduction at F 3ears in t,e 6innis, Diabetes #re0ention Stud3 7D#S9 7:E9, and !:I reduction at %) 3ears in t,e U.S. Diabetes #re0ention #rogra+ Outco+es Stud3 7D##OS9 7:B9. A cost/ e**ecti0eness +odel suggested t,at li*est3le inter0entions as deli0ered in t,e D## are cost/e**ecti0e 7H)9, and actual cost data *ro+ t,e D## and D##OS con5r+ t,at li*e/ st3le inter0entions are ,ig,l3 cost/e**ecti0e 7H%9. Crou. deli0er3 o* t,e D## inter0en/ tion in co++unit3 settings ,as t,e .oten/ tial to be signi5cantl3 less e2.ensi0e 4,ile still ac,ie0ing si+ilar 4eig,t loss 7H(9. Based on t,e results o* clinical trials and t,e 1no4n ris1s o* .rogression o* .rediabetes to diabetes, .ersons 4it, an

A%C o* H.F8".:I, ICT, or I6C s,ould be counseled on li*est3le c,anges 4it, goals si+ilar to t,ose o* t,e D## 7FI 4eig,t loss and +oderate .,3sical acti0it3 o* at least %H) +in@4ee19. Regarding drug t,era.3 *or diabetes .re0ention, +et*or/ +in ,as a strong e0idence base and de+/ onstrated long/ter+ sa*et3 7H!9. 6or ot,er drugs, issues o* cost, side e**ects, and lac1 o* .ersistence o* e**ect in so+e studies 7H:9 re-uire consideration. et*or+in 4as less e**ecti0e t,an li*est3le +odi5ca/ tion in t,e D## and D##OS, but +a3 be cost/sa0ing o0er a %)/3ear .eriod 7H%9. It 4as as e**ecti0e as li*est3le +odi5cation in .artici.ants 4it, a B I o* at least !H ( 1g@+ , but not signi5cantl3 better t,an .lacebo t,an t,ose o0er age ") 3ears 7(!9. In 4o+en in t,e D## 4it, a ,istor3 o* CD , +et*or+in and intensi0e li*est3le +odi5cation led to an e-ui0alent H)I re/ duction in t,e ris1 o* diabetes 7HH9. et/ *or+in t,ere*ore +ig,t reasonabl3 be reco++ended *or 0er3 ,ig,/ris1 indi0id/ uals 7t,ose 4it, a ,istor3 o* CD , t,e 0er3 obese, and@or t,ose 4it, +ore se0ere or .rogressi0e ,3.ergl3ce+ia9. #eo.le 4it, .rediabetes o*ten ,a0e ot,er cardio0ascular ris1 *actors, suc, as obesit3, ,3.ertension, and d3sli.ide+ia. Assessing and treating t,ese ris1 *actors is an i+.ortant as.ect o* reducing cardio/ +etabolic ris1. In t,e D## and D##OS, cardio0ascular e0ent rates ,a0e been 0er3 lo4, .er,a.s due to a..ro.riate +anage/ +ent o* cardio0ascular ris1 *actors in all ar+s o* t,e stud3 7H"9. V. DIABETES CARE A. Initial e0aluation A co+.lete +edical e0aluation s,ould be .er*or+ed to classi*3 t,e diabetes, detect t,e .resence o* diabetes co+.lications, re0ie4 .re0ious treat+ent and ris1 *actor control in .atients 4it, establis,ed diabe/ tes, assist in *or+ulating a +anage+ent .lan, and .ro0ide a basis *or continuing care. Laborator3 tests a..ro.riate to t,e e0aluation o* eac, .atient<s +edical condi/ tion s,ould be .er*or+ed. A *ocus on t,e co+.onents o* co+.re,ensi0e care 7Table F9 4ill assist t,e ,ealt, care tea+ to ensure o.ti+al +anage+ent o* t,e .atient 4it, diabetes. B. anage+ent #eo.le 4it, diabetes s,ould recei0e +ed/ ical care *ro+ a tea+ t,at +a3 include

.,3sicians, nurse .ractitioners, .,3sician<s assistants, nurses, dietitians, .,ar+acists, and +ental ,ealt, .ro*essionals 4it,

Table FdCo+.onents o* t,e co+.re,ensi0e diabetes e0aluation edical ,istor3 c Age and c,aracteristics o* onset o* diabetes 7e.g., DQA, as3+.to+atic laborator3 5nding9 c Eating .atterns, .,3sical acti0it3 ,abits, nutritional status, and 4eig,t ,istor3O gro4t, and de0elo.+ent in c,ildren and adolescents c Diabetes education ,istor3 c Re0ie4 o* .re0ious treat+ent regi+ens and res.onse to t,era.3 7A%C records9 c Current treat+ent o* diabetes, including +edications, +edication ad,erence and barriers t,ereto, +eal .lan, .,3sical acti0it3 .atterns, and readiness *or be,a0ior c,ange c Results o* glucose +onitoring and .atient<s use o* data c DQA *re-uenc3, se0erit3, and cause c D3.ogl3ce+ic e.isodes c D3.ogl3ce+ia a4areness c An3 se0ere ,3.ogl3ce+ia> *re-uenc3 and cause c Distor3 o* diabetes/related co+.lications c icro0ascular> retino.at,3, ne.,ro.at,3, neuro.at,3 7sensor3, including ,istor3 o* *oot lesionsO autono+ic, including se2ual d3s*unction and gastro.aresis9 c acro0ascular> CDD, cerebro0ascular disease, and #AD c Ot,er> .s3c,osocial .roble+sN, dental diseaseN #,3sical e2a+ination c Deig,t, 4eig,t, B I c Blood .ressure deter+ination, including ort,ostatic +easure+ents 4,en indicated c 6undosco.ic e2a+inationN c T,3roid .al.ation c S1in e2a+ination 7*or acant,osis nigricans and insulin injection sites9 c Co+.re,ensi0e *oot e2a+ination c Ins.ection c #al.ation o* dorsalis .edis and .osterior tibial .ulses c #resence@absence o* .atellar and Ac,illes reAe2es c Deter+ination o* .ro.rioce.tion, 0ibration, and +ono5la+ent sensation Laborator3 e0aluation c A%C, i* results not a0ailable 4it,in .ast (8! +ont,s I* not .er*or+ed@a0ailable 4it,in .ast 3ear c 6asting li.id .ro5le, including total, LDL and DDL c,olesterol and trigl3cerides c Li0er *unction tests c Test *or urine albu+in e2cretion 4it, s.ot urine albu+in/to/creatinine ratio c Seru+ creatinine and calculated C6R c TSD in t3.e % diabetes, d3sli.ide+ia or 4o+en o0er age H) 3ears Re*errals c E3e care .ro*essional *or annual dilated e3e e2a+ c 6a+il3 .lanning *or 4o+en o* re.roducti0e age c Registered dietitian *or $T c DS E c Dentist *or co+.re,ensi0e .eriodontal e2a+ination c ental ,ealt, .ro*essional, i* needed
NSee a..ro.riate re*errals *or t,ese categories.

and conditions, .,3sical acti0it3, eating .atterns, social situation and cultural *ac/ tors, and .resence o* co+.lications o* di/ abetes or ot,er +edical conditions. C. Cl3ce+ic control %. Assess+ent o* gl3ce+ic control T4o .ri+ar3 tec,ni-ues are a0ailable *or ,ealt, .ro0iders and .atients to assess t,e e**ecti0eness o* t,e +anage+ent .lan on gl3ce+ic control> .atient sel*/+onitoring o* blood glucose 7S BC9 or interstitial glucose, and A%C.

e2.ertise and a s.ecial interest in diabetes. It is essential in t,is collaborati0e and in/ tegrated tea+

a. Clucose +onitoring Reco++endations c #atients on +ulti.le/dose insulin 7 DI9 or insulin .u+. t,era.3 s,ould do S BC at least .rior to +eals and snac1s, occasionall3 .ost.randiall3, at bedti+e, .rior to e2ercise, 4,en t,e3 sus.ect lo4 blood glucose, a*ter treating lo4 blood glucose until t,e3 are nor+ogl3ce+ic, and .rior to critical tas1s suc, as dri0/ ing. 7B9 c K,en .rescribed as .art o* a broader educational conte2t, S BC results +a3 be ,el.*ul to guide treat+ent decisions and@or .atient sel*/ +anage+ent *or .atients using less *re-uent insulin in/ jections or noninsulin t,era.ies. 7E9 c K,en .rescribing S BC, ensure t,at .atients recei0e ongoing instruction and regular e0aluation o* S BC tec,/ ni-ue and S BC results, as 4ell as t,eir abilit3 to use S BC data to adjust t,er/ a.3. 7E9 c Continuous glucose +onitoring 7CC 9 in conjunction 4it, intensi0e insulin regi+ens can be a use*ul tool to lo4er A%C in selected adults 7aged J(H 3ears9 4it, t3.e % diabetes. 7A9 c Alt,oug, t,e e0idence *or A%C lo4er/ ing is less strong in c,ildren, teens, and 3ounger adults, CC +a3 be ,el.*ul in t,ese grou.s. Success correlates 4it, ad,erence to ongoing use o* t,e de0ice. 7C9 c CC +a3 be a su..le+ental tool to be *or+ulated as a collaborati0e a..roac, t,at indi0iduals 4it, diabetes assu+e an acti0e role in t,eir care. t,era.eutic T,e +anage+ent .lan s,ould alliance a+ong t,e .atient and *a+il3,

t,e .,3sician, and ot,er +e+bers o* t,e ,ealt, care tea+. A 0ariet3 o* strategies and tec,ni-ues s,ould be used to .ro0ide ade-uate education and de0elo.+ent

o* .roble+/sol0ing s1ills in t,e 0arious as.ects o* diabetes +anage+ent. I+.le/ +entation o* t,e +anage+ent .lan re/ -uires t,at t,e goals and treat+ent .lan are indi0iduali;ed and ta1e .atient .re*/ erences into account. T,e +anage+ent .lan s,ould recogni;e diabetes sel*/ +anage+ent education 7DS E9 and on/ going diabetes su..ort as an integral co+.onent o* care. In de0elo.ing t,e .lan, consideration s,ould be gi0en to t,e .atient<s age, sc,ool or 4or1 sc,edule

S BC in t,ose 4it, ,3.ogl3ce+ia una4areness and@or *re-uent ,3.ogl3/ ce+ic e.isodes. 7E9 ajor clinical trials o* insulin/ treated .atients t,at de+onstrated t,e bene5ts o* intensi0e gl3ce+ic control on diabetes co+.lications ,a0e included S BC as .art o* +ulti*actorial inter0entions, sug/ gesting t,at S BC is a co+.onent o* e**ecti0e t,era.3. S BC allo4s .atients to e0aluate t,eir indi0idual res.onse to

t,era.3 and assess 4,et,er gl3ce+ic tar/ gets are being ac,ie0ed. Results o* S BC can be use*ul in .re0enting ,3.ogl3ce+ia and adjusting +edications 7.articularl3 .randial insulin doses9, +edical nutrition t,era.3 7 $T9, and .,3sical acti0it3. T,e *re-uenc3 and ti+ing o* S BC s,ould be dictated b3 t,e .articular needs and goals o* t,e .atient. S BC is es.e/ ciall3 i+.ortant *or .atients treated 4it, insulin to +onitor *or and .re0ent as3+./ to+atic ,3.ogl3ce+ia and ,3.ergl3ce/ +ia. ost .atients 4it, t3.e % diabetes and ot,ers on intensi0e insulin regi+ens 7 DI or insulin .u+. t,era.39 s,ould do S BC at least .rior to +eals and snac1s, occasionall3 .ost.randiall3, at bedti+e, .rior to e2ercise, 4,en t,e3 sus.ect lo4 blood glucose, a*ter treating lo4 blood glucose until t,e3 are nor+ogl3ce+ic, and .rior to critical tas1s suc, as dri0ing. 6or +an3 .atients, t,is 4ill re-uire test/ ing "8E ti+es dail3, alt,oug, indi0idual needs +a3 be greater. Alt,oug, t,ere are *e4 rigorous studies, a database stud3 o* al+ost (F,))) c,ildren and adolescents 4it, t3.e % diabetes s,o4ed t,at, a*ter adjust+ent *or +ulti.le con*ounders, in/ creased dail3 *re-uenc3 o* S BC 4as sig/ ni5cantl3 associated 4it, lo4er A%C 7().(I .er additional test .er da3, le0el/ ing o** at 50e tests .er da39 and 4it, *e4er acute co+.lications 7HF9. T,e o.ti+al *re-uenc3 o* S BC *or .atients on non/ intensi0e regi+ens, suc, as t,ose 4it, t3.e ( diabetes on basal insulin, is not 1no4n, alt,oug, a nu+ber o* studies ,a0e used *asting S BC *or .atient or .ro/ 0ider titration o* t,e basal insulin dose. T,e e0idence base *or S BC *or .atients 4it, t3.e ( diabetes on noninsulin t,era.3 is so+e4,at +i2ed. Se0eral rando+i;ed trials ,a0e called into -uestion t,e clinical utilit3 and cost/ e**ecti0eness o* routine S BC in non8insulin/treated .atients 7HE8")9. A recent +eta/anal3sis suggested t,at S BC reduced A%C b3 ).(HI at " +ont,s 7"%9, 4,ile a Coc,rane re0ie4 con/ cluded t,at t,e o0erall e**ect o* S BC in suc, .atients is s+all u. to " +ont,s a*ter initiation and subsides a*ter %( +ont,s 7"(9.

Because t,e accurac3 o* S BC is instru+ent and user de.endent 7"!9, it is i+.ortant to e0aluate eac, .atient<s +onitoring tec,ni-ue, bot, initiall3 and at regular inter0als t,erea*ter. O.ti+al use o* S BC re-uires .ro.er re0ie4 and inter.retation o* t,e data, bot, b3 t,e .a/ tient and .ro0ider. A+ong .atients 4,o c,ec1ed t,eir blood glucose at least once dail3, +an3 re.orted ta1ing no action 4,en results 4ere ,ig, or lo4 7":9. In

one stud3 o* insulin/naR0e .atients 4it, subo.ti+al initial gl3ce+ic control, use o* structured S BC 7a .a.er tool to col/ lect and inter.ret F/.oint S BC .ro5les o0er ! da3s at least -uarterl39 reduced A%C b3 ).!I +ore t,an in an acti0e con/ trol grou. 7"H9. #atients s,ould be taug,t ,o4 to use S BC data to adjust *ood in/ ta1e, e2ercise, or .,ar+acological t,era.3 to ac,ie0e s.eci5c goals, and t,e ongoing need *or and *re-uenc3 o* S BC s,ould be re/e0aluated at eac, routine 0isit. Real/ti+e CC t,roug, t,e +easure/ +ent o* interstitial glucose 74,ic, corre/ lates 4ell 4it, .las+a glucose9 is a0ailable. T,ese sensors re-uire calibration 4it, S BC, and t,e latter are still reco++ended *or +a1ing acute treat+ent decisions. CC de0ices ,a0e alar+s *or ,3.o/ and ,3.ergl3ce+ic e2cursions. A ("/4ee1 ran/ do+i;ed trial o* !(( t3.e % diabetic .a/ tients s,o4ed t,at adults aged J(H 3ears using intensi0e insulin t,era.3 and CC e2.erienced a ).HI reduction in A%C 7*ro+ OF." to F.%I9 co+.ared 4it, usual intensi0e insulin t,era.3 4it, S BC 7""9. Sensor use in c,ildren, teens, and adults to age (: 3ears did not result in signi5cant A%C lo4ering, and t,ere 4as no signi5cant di**erence in ,3.ogl3ce+ia in an3 grou.. I+.ortantl3, t,e greatest .redictor o* A%C lo4ering in t,is stud3 *or all age/grou.s 4as *re-uenc3 o* sensor use, 4,ic, 4as lo4er in 3ounger age/grou.s. In a s+aller RCT o* %(B adults and c,ildren 4it, base/ line A%C ,F.)I, outco+es co+bining A%C and ,3.ogl3ce+ia *a0ored t,e grou. utili;ing CC , suggesting t,at CC is also bene5cial *or indi0iduals 4it, t3.e % dia/ betes 4,o ,a0e alread3 ac,ie0ed e2cellent control 7"F9. A trial co+.aring CC .lus insulin .u+. to S BC .lus +ulti.le injections o* insulin in adults and c,ildren 4it, t3.e % diabetes s,o4ed signi5cantl3 greater i+.ro0e+ents in A%C 4it, =sensor/ aug+ented .u+.? t,era.3 7"E,"B9, but t,is trial did not isolate t,e e**ect o* CC itsel*. O0erall, +eta/anal3ses suggest t,at co+.ared 4it, S BC, CC lo4ers A%C b3 O).("I 7F)9. Altoget,er, t,ese data suggest t,at, in a..ro.riatel3 selected .a/ tients 4,o are +oti0ated to 4ear it +ost o* t,e ti+e, CC reduces A%C. T,e tec,nol/ og3 +a3 be .articularl3 use*ul in t,ose 4it, ,3.ogl3ce+ia una4areness and@or *re/ -uent e.isodes o* ,3.ogl3ce+ia, alt,oug, studies as 3et ,a0e not s,o4n signi5cant reductions in se0ere ,3.ogl3ce+ia 7F)9. CC *or+s t,e under.inning *or t,e de/ 0elo.+ent o* .u+.s t,at sus.end insulin deli0er3 4,en ,3.ogl3ce+ia is de0elo.ing

and *or t,e burgeoning 4or1 on =arti5cial .ancreas? s3ste+s. b. A%C Reco++endations c #er*or+ t,e A%C test at least t4o ti+es a 3ear in .atients 4,o are +eet/ ing treat+ent goals 7and 4,o ,a0e stable gl3ce+ic control9. 7E9 c #er*or+ t,e A%C test -uarterl3 in .a/ tients 4,ose t,era.3 ,as c,anged or 4,o are not +eeting gl3ce+ic goals. 7E9 c Use o* #OC testing *or A%C .ro0ides t,e o..ortunit3 *or +ore ti+el3 treat/ +ent c,anges. 7E9 Because A%C is t,oug,t to reAect a0er/ age gl3ce+ia o0er se0eral +ont,s 7"!9 and ,as strong .redicti0e 0alue *or diabetes co+.lications 7F%,F(9, A%C testing s,ould be .er*or+ed routinel3 in all .a/ tients 4it, diabetes, at initial assess+ent and t,en as .art o* continuing care. ea/ sure+ent a..ro2i+atel3 e0er3 ! +ont,s deter+ines 4,et,er .atient<s gl3ce+ic tar/ gets ,a0e been reac,ed and +aintained. 6or an3 indi0idual .atient, t,e *re-uenc3 o* A%C testing s,ould be de.endent on t,e clinical situation, t,e treat+ent regi+en used, and t,e judg+ent o* t,e clinician. So+e .atients 4it, stable gl3ce+ia 4ell 4it,in target +a3 do 4ell 4it, testing onl3 t4ice .er 3ear, 4,ile unstable or ,ig,l3 intensi0el3 +anaged .atients 7e.g., .regnant t3.e % diabetic 4o+en9 +a3 be tested +ore *re-uentl3 t,an e0er3 ! +ont,s. T,e a0ailabilit3 o* t,e A%C result at t,e ti+e t,at t,e .atient is seen 7#OC testing9 ,as been re.orted in s+all studies to result in increased intensi5cation o* t,er/ a.3 and i+.ro0e+ent in gl3ce+ic control 7F!,F:9. Do4e0er, t4o recent s3ste+atic re0ie4s and +eta/anal3ses *ound no signi*/ icant di**erence in A%C bet4een #OC and laborator3 A%C usage 7FH,F"9. T,e A%C test is subject to certain li+itations. Conditions t,at a**ect er3t,/ roc3te turno0er 7,e+ol3sis, blood loss9 and ,e+oglobin 0ariants +ust be consid/ ered, .articularl3 4,en t,e A%C result does not correlate 4it, t,e .atient<s clin/ ical situation 7"!9. In addition, A%C does not .ro0ide a +easure o* gl3ce+ic 0ari/ abilit3 or ,3.ogl3ce+ia. 6or .atients .rone to gl3ce+ic 0ariabilit3 7es.eciall3 t3.e % diabetic .atients or t3.e ( diabetic .atients 4it, se0ere insulin de5cienc39, gl3ce+ic control is best judged b3 t,e co+bination o* results o* sel*/+onitoring and t,e A%C. T,e A%C +a3 also ser0e as a c,ec1 on t,e accurac3 o* t,e .atient<s +e/ ter 7or t,e .atient<s re.orted S BC

results9 and t,e ade-uac3 o* t,e S BC testing sc,edule. Table E contains t,e correlation be/ t4een A%C le0els and +ean .las+a glu/ cose le0els based on data *ro+ t,e international A%C/Deri0ed A0erage Clu/ cose 7ADAC9 trial utili;ing *re-uent S BC and CC in H)F adults 7E!I Cau/ casian9 4it, t3.e %, t3.e (, and no diabe/ tes 7FF9. T,e ADA and t,e A+erican Association *or Clinical C,e+istr3 ,a0e deter+ined t,at t,e correlation 7r H ).B(9 is strong enoug, to justi*3 re.orting bot, an A%C result and an esti+ated a0/ erage glucose 7eAC9 result 4,en a clini/ cian orders t,e A%C test. T,e table in .re/ ())B 0ersions o* t,e =Standards o* edi/ cal Care in Diabetes? describing t,e cor/ relation bet4een A%C and +ean glucose 4as deri0ed *ro+ relati0el3 s.arse data 7one F/.oint .ro5le o0er % da3 .er A%C reading9 in t,e .ri+aril3 Caucasian t3.e % diabetic .artici.ants in t,e DCCT 7FE9. Clinicians s,ould note t,at t,e nu+bers in t,e table are no4 di**erent, as t,e3 are based on O(,E)) readings .er A%C in t,e ADAC trial. In t,e ADAC trial, t,ere 4ere no sig/ ni5cant di**erences a+ong racial and et,/ nic grou.s in t,e regression lines bet4een A%C and +ean glucose, alt,oug, t,ere 4as a trend to4ard a di**erence bet4een A*rican@A*rican A+erican .artici.ants and Caucasian ones. A s+all stud3 co+/ .aring A%C to CC data in t3.e % di/ abetic c,ildren *ound a ,ig,l3 statisticall3 signi5cant correlation bet4een A%C and +ean blood glucose, alt,oug, t,e corre/ lation 7r H ).F9 4as signi5cantl3 lo4er t,an in t,e ADAC trial 7FB9. K,et,er
Table EdCorrelation o* A%C 4it, a0erage glucose ea n .l as +a g lu c os e A%C 7I9 " F E B %) %% %( +g@dL %(" %H: %E! (%( (:) ("B (B E ++ol@L F.) E." %).( %%.E %!.: %:.B %" .H

t,ere are signi5cant di**erences in ,o4 A%C relates to a0erage glucose in c,ildren or in A*rican A+erican .atients is an area *or *urt,er stud3. 6or t,e ti+e being, t,e -uestion ,as not led to di**erent reco+/ +endations about testing A%C or to di*/ *erent inter.retations o* t,e clinical +eaning o* gi0en le0els o* A%C in t,ose .o.ulations. 6or .atients in 4,o+ A%C@eAC and +easured blood glucose a..ear discre./ ant, clinicians s,ould consider t,e .ossi/ bilities o* ,e+oglobino.at,3 or altered red cell turno0er, and t,e o.tions o* +ore *re-uent and@or di**erent ti+ing o* S BC or use o* CC . Ot,er +easures o* c,ronic gl3ce+ia suc, as *ructosa+ine are a0ail/ able, but t,eir lin1age to a0erage glucose and t,eir .rognostic signi5cance are not as clear as is t,e case *or A%C. (. Cl3ce+ic goals in adults Reco++endations c Lo4ering A%C to belo4 or around FI ,as been s,o4n to reduce +icro0as/ cular co+.lications o* diabetes and i* i+.le+ented soon a*ter t,e diagnosis o* diabetes is associated 4it, long/ ter+ reduction in +acro0ascular disease. T,ere*ore, a reasonable A%C goal *or +an3 non.regnant adults is ,FI. 7B9 c #ro0iders +ig,t reasonabl3 suggest +ore stringent A%C goals 7suc, as ,".HI9 *or selected indi0idual .a/ tients, i* t,is can be ac,ie0ed 4it,out signi5cant ,3.ogl3ce+ia or ot,er ad/ 0erse e**ects o* treat+ent. A..ro.riate .atients +ig,t include t,ose 4it, s,ort duration o* diabetes, long li*e e2.ec/ tanc3, and no signi5cant CVD. 7C9 c Less stringent A%C goals 7suc, as ,EI9 +a3 be a..ro.riate *or .atients 4it, a ,istor3 o* se0ere ,3.ogl3ce+ia, li+ited li*e e2.ectanc3, ad0anced +i/ cro0ascular or +acro0ascular co+.lica/ tions, e2tensi0e co+orbid conditions, and t,ose 4it, long/standing diabetes in 4,o+ t,e general goal is di*5cult to at/ tain des.ite DS E, a..ro.riate glucose +onitoring, and e**ecti0e doses o* +ul/ ti.le glucose/lo4ering agents including insulin. 7B9
T,ese esti+ates are based on ADAC data o* O (,F)) glucose +easure+ents o0er ! +ont,s .er A%C +easure+ent in H)F adults 4it, t3.e

+icro0ascular 7retino.at,3 and ne.,ro/ .at,39 and neuro.at,ic co+.lications. 6ollo4/u. o* t,e DCCT co,orts in t,e E./ ide+iolog3 o* Diabetes Inter0entions and Co+.lications 7EDIC9 stud3 7E),E%9 de+/ onstrated .ersistence o* t,ese +icro0ascu/ lar bene5ts in .re0iousl3 intensi0el3 treated subjects, e0en t,oug, t,eir gl3ce+ic con/ trol a..ro2i+ated t,at o* .re0ious stan/ dard ar+ subjects during *ollo4/u.. T,e Qu+a+oto Stud3 7E(9 and UQ #ros.ecti0e Diabetes Stud3 7UQ#DS9 7E!,E:9 con5r+ed t,at intensi0e gl3ce+ic control 4as associated 4it, signi5cantl3 decreased rates o* +icro0ascular and neu/ ro.at,ic co+.lications in .atients 4it, t3.e ( diabetes. Long/ter+ *ollo4/u. o* t,e UQ#DS co,orts s,o4ed .ersistence o* t,e e**ect o* earl3 gl3ce+ic control on +ost +icro0ascular co+.lications 7EH9. Subse-uent trials in .atients 4it, +ore long/standing t3.e ( diabetes, de/ signed .ri+aril3 to loo1 at t,e role o* intensi0e gl3ce+ic control on cardio0as/ cular outco+es, also con5r+ed a bene5t, alt,oug, +ore +odest, on onset or .ro/ gression o* +icro0ascular co+.lications. T,e Veterans A**airs Diabetes Trial 7VADT9 s,o4ed signi5cant reductions in albu+inuria 4it, intensi0e 7ac,ie0ed +edian A%C ".BI9 co+.ared 4it, stan/ dard gl3ce+ic control, but no di**erence in retino.at,3 and neuro.at,3 7E",EF9. T,e Action in Diabetes and Vascular Dis/ ease> #retera2 and Dia+icron R Con/ trolled E0aluation 7ADVA$CE9 stud3 o* intensi0e 0ersus standard gl3ce+ic con/ trol in t3.e ( diabetes *ound a statisticall3 signi5cant reduction in albu+inuria, but not in neuro.at,3 or retino.at,3, 4it, an A%C target o* ,".HI 7ac,ie0ed +edian A%C ".!I9 co+.ared 4it, standard t,er/ a.3 ac,ie0ing a +edian A%C o* F.)I 7EE9. Anal3ses *ro+ t,e Action to Control Car/ dio0ascular Ris1 in Diabetes 7ACCORD9 trial ,a0e s,o4n lo4er rates o* onset or .rogression o* earl3/stage +icro0ascular co+.lications in t,e intensi0e control ar+ co+.ared 4it, t,e standard ar+ 7EB,B)9. E.ide+iological anal3ses o* t,e and UQ#DS 7F%,F(9 de+onstrate a linear relations,i. bet4een A%C and +i/ cro0ascular co+.lications. Suc,

D3.ergl3ce+ia de5nes diabetes, and

%, t3.e (, and no diabetes. T,e correlation bet4een A%C and a0/ erage glucose 4as ).B( 7re*. FF9. A calculator *or con0erting A%C results into

eAC, in eit,er +g@dL or ++ol@L, is a0ailable at ,tt.>@@.ro*essional.diabetes .org@eAC.

gl3ce+ic control is *unda+ental to t,e +anage+ent o* diabetes. T,e DCCT 7F%9, a .ros.ecti0e RCT o* intensi0e 0er/ sus standard gl3ce+ic control in .atients 4it, relati0el3 recentl3 diagnosed t3.e % diabetes, s,o4ed de5niti0el3 t,at i+.ro0ed gl3ce+ic control is associ/ ated 4it, signi5cantl3 decreased rates o*

suggest t,at, on a .o.ulation le0el, t,e greatest nu+ber o* co+.lications 4ill be a0erted b3 ta1ing .atients *ro+ 0er3 .oor control to *air or good control. T,ese anal/ 3ses also suggest t,at *urt,er lo4ering o* A%C *ro+ F to "I is associated 4it, *urt,er reduction in t,e ris1 o* +icro0ascular co+.lications, albeit t,e absolute ris1

reductions beco+e +uc, s+aller. Ci0en t,e substantiall3 increased ris1 o* ,3.ogl3/ ce+ia 7.articularl3 in t,ose 4it, t3.e % di/ abetes, but also in t,e recent t3.e ( diabetes trials9, t,e concerning +ortalit3 5ndings in t,e ACCORD trial 7B%9, and t,e relati0el3 +uc, greater e**ort re-uired to ac,ie0e near/nor+ogl3ce+ia, t,e ris1s o* lo4er gl3/ ce+ic targets +a3 out4eig, t,e .otential bene5ts on +icro0ascular co+.lications on a .o.ulation le0el. Do4e0er, selected indi0idual .atients, es.eciall3 t,ose 4it, little co+orbidit3 and long li*e e2.ectanc3 74,o +a3 rea. t,e bene5ts o* *urt,er lo4/ ering o* gl3ce+ia belo4 FI9, +a3, based on .ro0ider judg+ent and .atient .re*er/ ences, ado.t +ore intensi0e gl3ce+ic tar/ gets 7e.g., an A%C target ,".HI9 as long as signi5cant ,3.ogl3ce+ia does not beco+e a barrier. CVD, a +ore co++on cause o* deat, in .o.ulations 4it, diabetes t,an +icro/ 0ascular co+.lications, is less clearl3 i+.acted b3 le0els o* ,3.ergl3ce+ia or t,e intensit3 o* gl3ce+ic control. In t,e DCCT, t,ere 4as a trend to4ard lo4er ris1 o* CVD e0ents 4it, intensi0e control, and in B/3ear .ost/DCCT *ollo4/ u. o* t,e EDIC co,ort .artici.ants .re0iousl3 ran/ do+i;ed to t,e intensi0e ar+ ,ad a sig/ ni5cant HFI reduction in t,e ris1 o* non*atal +3ocardial in*arction 7 I9, stro1e, or CVD deat, co+.ared 4it, t,ose .re/ 0iousl3 in t,e standard ar+ 7B(9. T,e ben/ e5t o* intensi0e gl3ce+ic control in t,is t3.e % diabetic co,ort ,as recentl3 been s,o4n to .ersist *or se0eral decades 7B!9. In t3.e ( diabetes, t,ere is e0idence t,at +ore intensi0e treat+ent o* gl3ce+ia in ne4l3 diagnosed .atients +a3 reduce long/ter+ CVD rates. During t,e UQ#DS trial, t,ere 4as a %"I reduction in car/ dio0ascular e0ents 7co+bined *atal or non*atal I and sudden deat,9 in t,e intensi0e gl3ce+ic control ar+ t,at did not reac, statistical signi5cance 7# H ).)H(9, and t,ere 4as no suggestion o* bene5t on ot,er CVD outco+es suc, as stro1e. Do4e0er, a*ter %) 3ears o* *ollo4/ u., t,ose originall3 rando+i;ed to inten/ si0e gl3ce+ic control ,ad signi5cant long/ter+ reductions in I 7%HI 4it, sul*on3lurea or insulin as initial .,ar+a/ cot,era.3, !!I 4it, +et*or+in as initial .,ar+acot,era.39 and in all/cause +or/ talit3 7%!I and (FI, res.ecti0el39 7EH9. T,ree +ore recent large trials 7ACCORD, ADVA$CE, and VADT9 sug/ gested no signi5cant reduction in
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All t,ree o* t,ese trials 4ere conducted in .artici.ants 4it, +ore long/standing di/ abetes 7+ean duration E8%% 3ears9 and eit,er 1no4n CVD or +ulti.le cardio0as/ cular ris1 *actors. Details o* t,ese t,ree studies are re0ie4ed e2tensi0el3 in an ADA .osition state+ent 7B:9. T,e ACCORD stud3 enrolled .artici/ .ants 4it, eit,er 1no4n CVD or t4o or +ore +ajor cardio0ascular ris1 *actors and rando+i;ed t,e+ to intensi0e gl3ce/ +ic control 7goal A%C ,"I9 or standard gl3ce+ic control 7goal A%C F8EI9. T,e gl3ce+ic control co+.arison 4as ,alted earl3 due to t,e 5nding o* an increased rate o* +ortalit3 in t,e intensi0e ar+ co+/ .ared 4it, t,e standard ar+ 7%.:%I 0s. %.%:I .er 3earO DR %.((O BHI CI %.)%8 %.:"9, 4it, a si+ilar increase in cardio0as/ cular deat,s. T,is increase in +ortalit3 in t,e intensi0e gl3ce+ic control ar+ 4as seen in all .res.eci5ed .atient subgrou.s. T,e .ri+ar3 outco+e o* ACCORD 7non/ *atal I, non*atal stro1e, or cardio0ascu/ lar deat,9 4as nonsigni5cantl3 lo4er in t,e intensi0e gl3ce+ic control grou. due to a reduction in non*atal I, bot, 4,en t,e gl3ce+ic control co+.arison 4as ,alted and all .artici.ants transi/ tioned to t,e standard gl3ce+ic control inter0ention 7B%9, and at co+.letion o* t,e .lanned *ollo4/u. 7BH9. E2.lorator3 anal3ses o* t,e +ortalit3 5ndings o* ACCORD 7e0aluating 0ari/ ables including 4eig,t gain, use o* an3 s.eci5c drug or drug co+bination, and ,3.ogl3ce+ia9 4ere re.ortedl3 unable to identi*3 a clear e2.lanation *or t,e e2cess +ortalit3 in t,e intensi0e ar+ 7B%9. T,e ACCORD in0estigators subse-uentl3 .ublis,ed additional e.ide+iological anal3ses s,o4ing no increase in +ortalit3 in t,e intensi0e ar+ .artici.ants 4,o ac,ie0ed A%C le0els belo4 FI nor in t,ose 4,o lo4ered t,eir A%C -uic1l3 a*/ ter trial enroll+ent. In *act, alt,oug, t,ere 4as no A%C le0el at 4,ic, intensi0e ar+ .artici.ants ,ad signi5cantl3 lo4er +or/ talit3 t,an standard ar+ .artici.ants, t,e ,ig,est ris1 *or +ortalit3 4as obser0ed in intensi0e ar+ .artici.ants 4it, t,e ,ig,/ est A%C le0els 7B"9. T,e role o* ,3.ogl3ce+ia in t,e e2/ cess +ortalit3 5ndings 4as also co+.le2. Se0ere ,3.ogl3ce+ia 4as signi5cantl3 +ore li1el3 in .artici.ants rando+i;ed to t,e intensi0e gl3ce+ic control ar+. Do4e0er, e2cess +ortalit3 in t,e inten/ si0e 0ersus standard ar+s 4as onl3 sig/ ni5cant *or .artici.ants 4it, no se0ere ,3.ogl3ce+ia, and not *or t,ose 4it, one or +ore e.isodes. Se0ere ,3.ogl3ce+ia

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4as associated 4it, e2cess +ortalit3 in eit,er ar+, but t,e association 4as stron/ ger in t,ose rando+i;ed to t,e standard gl3ce+ic control ar+ 7BF9. Unli1e t,e case 4it, t,e DCCT trial, 4,ere lo4er ac,ie0ed A%C le0els 4ere related to sig/ ni5cantl3 increased rates o* se0ere ,3.o/ gl3ce+ia, in ACCORD e0er3 %I decline in A%C *ro+ baseline to : +ont,s into t,e trial 4as associated 4it, a signi5cant de/ crease in t,e rate o* se0ere ,3.ogl3ce+ia in bot, ar+s 7B"9. T,e .ri+ar3 outco+e o* ADVA$CE 4as a co+bination o* +icro0ascular e0ents 7ne.,ro.at,3 and retino.at,39 and +ajor ad0erse cardio0ascular e0ents 7 I, stro1e, and cardio0ascular deat,9. Intensi0e gl3ce+ic control 7to a goal A%C ,".HI 0s. treat+ent to local standards9 signi5cantl3 reduced t,e .ri+ar3 end .oint. Do4e0er, t,is 4as due to a signi5cant reduction in t,e +icro0ascular outco+e, .ri/ +aril3 de0elo.+ent o* +acroalbu+inuria, 4it, no signi5cant reduction in t,e +acro/ 0ascular outco+e. T,ere 4as no di**erence in o0erall or cardio0ascular +ortalit3 be/ t4een t,e intensi0e co+.ared 4it, t,e standard gl3ce+ic control ar+s 7EE9. T,e VADT rando+i;ed .artici.ants 4it, t3.e ( diabetes uncontrolled on insulin or +a2i+al/dose oral agents 7+e/ dian entr3 A%C B.:I9 to a strateg3 o* intensi0e gl3ce+ic control 7goal A%C ,".)I9 or standard gl3ce+ic control, 4it, a .lanned A%C se.aration o* at least %.HI. T,e .ri+ar3 outco+e o* t,e VADT 4as a co+.osite o* CVD e0ents. T,e cu/ +ulati0e .ri+ar3 outco+e 4as nonsig/ ni5cantl3 lo4er in t,e intensi0e ar+ 7E"9. An ancillar3 stud3 o* t,e VADT de+onstrated t,at intensi0e gl3ce+ic control signi5cantl3 reduced t,e .ri+ar3 CVD outco+e in indi0iduals 4it, less at,erosclerosis at baseline 7assessed b3 coronar3 calciu+9 but not in .ersons 4it, +ore e2tensi0e baseline at,eroscle/ rosis 7BE9. A .ost ,oc anal3sis s,o4ed a co+.le2 relations,i. bet4een duration o* diabetes be*ore gl3ce+ic intensi5ca/ tion and +ortalit3> +ortalit3 in t,e inten/ si0e 0s. standard gl3ce+ic control ar+ 4as in0ersel3 related to duration o* dia/ betes at t,e ti+e o* stud3 enroll+ent. T,ose 4it, diabetes duration less t,an %H 3ears ,ad a +ortalit3 bene5t in t,e in/ tensi0e ar+, 4,ile t,ose 4it, duration o* () 3ears or +ore ,ad ,ig,er +ortalit3 in t,e intensi0e ar+ 7BB9. T,e e0idence *or a cardio0ascular ben/ e5t o* intensi0e gl3ce+ic control .ri+aril3 rests on long/ter+ *ollo4/u. care.diabetesjournals.org

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% and t3.e ( diabetes and subset anal3ses o* ACCORD, ADVA$CE, and VADT. A grou./le0el +eta/anal3sis o* t,e latter t,ree trials suggests t,at glucose lo4ering ,as a +odest 7BI9 but statisticall3 signi5cant reduction in +ajor CVD outco+es, .ri/ +aril3 non*atal I, 4it, no signi5cant e**ect on +ortalit3. Do4e0er, ,eterogeneit3 o* t,e +ortalit3 e**ects across studies 4as noted, .recluding 5r+ su++ar3 +easures o* t,e +ortalit3 e**ects. A .res.eci5ed sub/ grou. anal3sis suggested t,at +ajor CVD outco+e reduction occurred in .atients 4it,out 1no4n CVD at baseline 7DR ).E:, BHI CI ).F:8).B:9 7%))9. Con0ersel3, t,e +ortalit3 5ndings in ACCORD and sub/ grou. anal3ses o* t,e VADT suggest t,at t,e .otential ris1s o* intensi0e gl3ce+ic control +a3 out4eig, its bene5ts in so+e .atients, suc, as t,ose 4it, 0er3 long du/ ration o* diabetes, 1no4n ,istor3 o* se0ere ,3.ogl3ce+ia, ad0anced at,erosclerosis, and ad0anced age@*railt3. Certainl3, .ro0id/ ers s,ould be 0igilant in .re0enting se0ere ,3.ogl3ce+ia in .atients 4it, ad0anced disease and s,ould not aggressi0el3 at/ te+.t to ac,ie0e near/nor+al A%C le0els in .atients in 4,o+ suc, a target cannot be sa*el3 and reasonabl3 easil3 ac,ie0ed. Se0ere or *re-uent ,3.ogl3ce+ia is an ab/ solute indication *or t,e +odi5cation o* treat+ent regi+ens, including setting ,ig,er gl3ce+ic goals. an3 *actors, in/ cluding .atient .re*erences, s,ould be ta1en into account 4,en de0elo.ing a .a/ tient<s indi0iduali;ed goals 7%)%9. Reco++ended gl3ce+ic goals *or +an3 non.regnant adults are s,o4n in Table B. T,e reco++endations are based on t,ose *or A%C 0alues, 4it, listed blood glucose le0els t,at a..ear to correlate 4it, ac,ie0e+ent o* an A%C o* ,FI.

T,e issue o* .re/ 0ersus .ost.randial S BC targets is co+.le2 7%)(9. Ele0ated .ostc,allenge 7(/, OCTT9 glucose 0alues ,a0e been associated 4it, increased car/ dio0ascular ris1 inde.endent o* 6#C in so+e e.ide+iological studies. In diabetic subjects, so+e surrogate +easures o* 0ascular .at,olog3, suc, as endot,elial d3s*unction, are negati0el3 a**ected b3 .ost.randial ,3.ergl3ce+ia 7%)!9. It is clear t,at .ost.randial ,3.ergl3ce+ia, li1e .re.randial ,3.ergl3ce+ia, contrib/ utes to ele0ated A%C le0els, 4it, its rela/ ti0e contribution being ,ig,er at A%C le0els t,at are closer to FI. Do4e0er, outco+e studies ,a0e clearl3 s,o4n A%C to be t,e .ri+ar3 .redictor o* co+/ .lications, and land+ar1 gl3ce+ic con/ trol trials suc, as t,e DCCT and UQ#DS relied o0er4,el+ingl3 on .re.randial S BC. Additionall3, an RCT in .atients 4it, 1no4n CVD *ound no CVD bene5t o* insulin regi+ens targeting .ost.ran/ dial glucose co+.ared 4it, t,ose targeting .re.randial glucose 7%):9. A reasonable reco++endation *or .ost/ .randial testing and targets is t,at *or in/ di0iduals 4,o ,a0e .re+eal glucose 0alues 4it,in target but ,a0e A%C 0alues abo0e target, +onitoring .ost.randial .las+a glucose 7##C9 %8( , a*ter t,e start o* t,e +eal and treat+ent ai+ed at reduc/ ing ##C 0alues to ,%E) +g@dL +a3 ,el. lo4er A%C. Cl3ce+ic goals *or c,ildren are .ro/ 0ided in Section VIII.A.%.a. As regards goals *or gl3ce+ic control *or 4o+en 4it, CD , reco++endations *ro+ t,e 6i*t, International Kor1s,o./ Con*erence on Cestational Diabetes ellitus 7%)H9 4ere to target +aternal ca.illar3 glucose con/ centrations o*>

.re.randial> SBH +g@dL 7H.! ++ol@L9, and eit,er> c %/, .ost+eal> S%:) +g@dL 7F.E ++ol@L9 or c (/, .ost+eal> S%() +g@dL 7".F ++ol@L9
c

6or 4o+en 4it, .re/e2isting t3.e % or t3.e ( diabetes 4,o beco+e .regnant, a recent consensus state+ent 7%)"9 reco+/ +ended t,e *ollo4ing as o.ti+al gl3ce+ic goals, i* t,e3 can be ac,ie0ed 4it,out e2/ cessi0e ,3.ogl3ce+ia>
c c c

.re+eal, bedti+e, and o0ernig,t glu/ cose ")8BB +g@dL 7!.!8H.: ++ol@L9 .ea1 .ost.randial glucose %))8%(B +g@dL 7H.:8F.% ++ol@L9 A%C ,".)I

D. #,ar+acological and o0erall a..roac,es to treat+ent %. Insulin t,era.3 *or t3.e % diabetes Reco++endations c ost .eo.le 4it, t3.e % diabetes s,ould be treated 4it, DI injections 7t,ree to *our injections .er da3 o* basal and .randial insulin9 or continuous sub/ cutaneous insulin in*usion 7CSII9. 7A9 c ost .eo.le 4it, t3.e % diabetes s,ould be educated in ,o4 to +atc, .randial insulin dose to carbo,3drate inta1e, .re+eal blood glucose, and antici.ated acti0it3. 7E9 c ost .eo.le 4it, t3.e % diabetes s,ould use insulin analogs to reduce ,3.ogl3ce+ia ris1. 7A9 c Consider screening t,ose 4it, t3.e % diabetes *or ot,er autoi++une dis/ eases 7t,3roid, 0ita+in B%( de5cienc3, celiac9 as a..ro.riate. 7B9
no t +e t de s. i te re a c ,i ng .r e .r a nd ia l g lu c os e go a ls
T#ost.randial glucose +easure+ents s,ould be +ade %8( , a*ter t,e beginning o* t,e +eal, generall3 .ea1 le0els in .atients 4it, diabetes.

Table BdSu++ar3 o* gl3ce+ic reco++endations *or +an3 non.regnant adults 4it, diabetes A%C ,F.)IN #re.randial ca.illar3 .las+a glucose F)8%!) +g@dLN 7!.B8F.( ++ol@L9 #ea1 .ost.randial ca.illar3 .las+a glucoseT ,%E) +g@dLN 7,%).) ++ol@L9 c NCoals s,ould be indi0iduali;ed based on> c duration o* diabetes c age@li*e e2.ectanc3 c co+orbid conditions c 1no4n CVD or ad0anced +icro0ascular co+.lications c ,3.ogl3ce+ia una4areness c indi0idual .atient considerations c ore or less stringent gl3ce+ic goals +a3 be a..ro.riate *or indi0idual .atients c #ost.randial glucose +a3 be targeted i* A%C goals are

T,e DCCT clearl3 s,o4ed t,at inten/ si0e insulin t,era.3 7t,ree or +ore in/ jections .er da3 o* insulin, CSII, or insulin .u+. t,era.39 4as a 1e3 .art o* i+/ .ro0ed gl3ce+ia and better outco+es 7F%,B(9. At t,e ti+e o* t,e stud3, t,era.3 4as carried out 4it, s,ort/ and inter+edi/ ate/acting ,u+an insulins. Des.ite better +icro0ascular outco+es, intensi0e insulin t,era.3 4as associated 4it, a ,ig, rate in se0ere ,3.ogl3ce+ia 7"( e.isodes .er %)) .atient/3ears o* t,era.39. Since t,e ti+e o* t,e DCCT, a nu+ber o* ra.id/acting and long/acting insulin analogs ,a0e been de/ 0elo.ed. T,ese analogs are associated 4it, less ,3.ogl3ce+ia 4it, e-ual A%C lo4er/ ing in t3.e % diabetes 7%)F,%)E9. Reco++ended t,era.3 *or t3.e % di/ abetes consists o* t,e *ollo4ing co+.onents>

%9 use o* DI injections 7t,ree to *our in/ jections .er da3 o* basal and .randial in/ sulin9 or CSII t,era.3O (9 +atc,ing o* .randial insulin to carbo,3drate inta1e, .re+eal blood glucose, and antici.ated acti0it3O and !9 *or +ost .atients 7es.e/ ciall3 i* ,3.ogl3ce+ia is a .roble+9, use o* insulin analogs. T,ere are e2cellent re/ 0ie4s a0ailable t,at guide t,e initiation and +anage+ent o* insulin t,era.3 to ac,ie0e desired gl3ce+ic goals 7%)F,%)B,%%)9. Alt,oug, +ost studies o* DI 0ersus .u+. t,era.3 ,a0e been s+all and o* s,ort duration, a s3ste+atic re0ie4 and +eta/anal3sis concluded t,at t,ere 4ere no s3ste+atic di**erences in A%C or rates o* se0ere ,3.ogl3ce+ia in c,ildren and adults bet4een t,e t4o *or+s o* inten/ si0e insulin t,era.3 7F)9. Because o* t,e increased *re-uenc3 o* ot,er autoi++une diseases in t3.e % diabetes, screening *or t,3roid d3s*unc/ tion, 0ita+in B%( de5cienc3, or celiac disease s,ould be considered based on signs and s3+.to+s. #eriodic screening in absence o* s3+.to+s ,as been reco+/ +ended, but t,e e**ecti0eness and o.ti/ +al *re-uenc3 are unclear. (. #,ar+acological t,era.3 *or ,3.er/ gl3ce+ia in t3.e ( diabetes Reco++endations c et*or+in, i* not contraindicated and i* tolerated, is t,e .re*erred initial .,ar+a/ cological agent *or t3.e ( diabetes. 7A9 c In ne4l3 diagnosed t3.e ( diabetic .atients 4it, +ar1edl3 s3+.to+atic and@or ele0ated blood glucose le0els or A%C, consider insulin t,era.3, 4it, or 4it,out additional agents, *ro+ t,e outset. 7E9 c I* noninsulin +onot,era.3 at +a2i+al tolerated dose does not ac,ie0e or +ain/ tain t,e A%C target o0er !8" +ont,s, add a second oral agent, a glucagon/ li1e .e.tide/% 7CL#/%9 rece.tor agonist, or insulin. 7A9 c A .atient/centered a..roac, s,ould be used to guide c,oice o* .,ar+acological agents. Considerations include e*5cac3, cost, .otential side e**ects, e**ects on 4eig,t, co+orbidities, ,3.ogl3ce+ia ris1, and .atient .re*erences. 7E9 c Due to t,e .rogressi0e nature o* t3.e ( diabetes, insulin t,era.3 is e0entuall3 indicated *or +an3 .atients 4it, t3.e ( diabetes. 7B9 T,e ADA and EASD ,a0e recentl3 .artnered on guidance *or indi0iduali;a/

tion o* use o* +edication classes diabetes 7%%%9. T,is ()%( .osition state/ and co+binations in .atients 4it, +ent is less .rescri.ti0e t,an .rior algo/ t3.e ( rit,+s and discusses ad0antages and disad0antages o* t,e a0ailable +edication classes and considerations *or t,eir use. A .atient/centered a..roac, is stressed, ta1ing into account .atient .re*erences, cost and .otential side e**ects o* eac, class, e**ects on bod3 4eig,t, and ,3.o/ gl3ce+ia ris1. T,e .osition state+ent re/ a*5r+s +et*or+in as t,e .re*erred initial agent, barring contraindication or intoler/ ance, eit,er in addition to li*est3le coun/ seling and su..ort *or 4eig,t loss and e2ercise, or 4,en li*est3le e**orts alone ,a0e not ac,ie0ed or +aintained gl3ce+ic goals. et*or+in ,as a long/standing e0idence base *or e*5cac3 and sa*et3, is ine2.ensi0e, and +a3 reduce ris1 o* car/ dio0ascular e0ents 7EH9. K,en +et*or+in *ails to ac,ie0e or +aintain gl3ce+ic goals, anot,er agent s,ould be added. Alt,oug, t,ere are a nu+ber o* trials co+.aring dual t,era.3 to +et*or+in alone, *e4 di/ rectl3 co+.are drugs as add/on t,era.3. Co+.arati0e e**ecti0eness +eta/anal3ses 7%%(9 suggest t,at o0erall eac, ne4 class o* noninsulin agents added to initial t,er/ a.3 lo4ers A%C around ).B8%.%I. an3 .atients 4it, t3.e ( diabetes e0entuall3 bene5t *ro+ insulin t,era.3. T,e .rogressi0e nature o* t3.e ( diabetes and its t,era.ies s,ould regularl3 be e2.lained in a +atter/o*/*act +anner to .atients, a0oiding using insulin as a t,reat or describing it as a *ailure or .unis,+ent. #ro0iding .atients 4it, an algorit,+ *or sel*/titration o* insulin doses based on S BC results i+.ro0es gl3ce+ic control in t3.e ( diabetic .atients initiating insulin 7%%!9. 6or +ore details on .,ar/ +acot,era.3 *or ,3.ergl3ce+ia in t3.e ( diabetes, including a table o* in*or+a/ tion about currentl3 a..ro0ed classes o* +edications *or treating ,3.ergl3ce/ +ia in t3.e ( diabetes, readers are re*erred to t,e ADA/EASD .osition state+ent 7%%%9. E. $T Ceneral reco++endations c Indi0iduals 4,o ,a0e .rediabetes or diabetes s,ould recei0e indi0iduali;ed $T as needed to ac,ie0e treat+ent goals, .re*erabl3 .ro0ided b3 a regis/ tered dietitian *a+iliar 4it, t,e co+/ .onents o* diabetes $T. 7A9 c Because $T can result in cost/sa0ings and i+.ro0ed outco+es 7B9, $T s,ould be ade-uatel3 co0ered b3 in/ surance and ot,er .a3ers. 7E9

Energ3 balance, o0er4eig,t, and obesit3 c Keig,t loss is reco++ended *or all o0er4eig,t or obese indi0iduals 4,o ,a0e or are at ris1 *or diabetes. 7A9 c 6or 4eig,t loss, eit,er lo4/carbo,3drate, lo4/*at calorie/restricted, or editerra/ nean diets +a3 be e**ecti0e in t,e s,ort/ ter+ 7u. to ( 3ears9. 7A9 c 6or .atients on lo4/carbo,3drate diets, +onitor li.id .ro5les, renal *unction, and .rotein inta1e 7in t,ose 4it, ne/ .,ro.at,39 and adjust ,3.ogl3ce+ic t,era.3 as needed. 7E9 c #,3sical acti0it3 and be,a0ior +odi5/ cation are i+.ortant co+.onents o* 4eig,t loss .rogra+s and are +ost ,el.*ul in +aintenance o* 4eig,t loss. 7B9 Reco++endations *or .ri+ar3 .re0ention o* t3.e ( diabetes c A+ong indi0iduals at ,ig, ris1 *or de/ 0elo.ing t3.e ( diabetes, structured .rogra+s t,at e+.,asi;e li*est3le c,anges t,at include +oderate 4eig,t loss 7FI bod3 4eig,t9 and regular .,3sical acti0it3 7%H) +in@4ee19, 4it, dietar3 strategies including reduced calories and reduced inta1e o* dietar3 *at, can reduce t,e ris1 *or de0elo.ing diabetes and are t,ere*ore reco+/ +ended. 7A9 c Indi0iduals at ris1 *or t3.e ( diabetes s,ould be encouraged to ac,ie0e t,e U.S. De.art+ent o* Agriculture 7USDA9 reco++endation *or dietar3 5ber 7%: g 5ber@%,))) 1cal9 and *oods containing 4,ole grains 7one/,al* o* grain inta1e9. 7B9 c Indi0iduals at ris1 *or t3.e ( diabetes s,ould be encouraged to li+it t,eir inta1e o* sugar/s4eetened be0erages 7SSBs9. 7B9 Reco++endations *or +anage+ent o* diabetes acronutrients in diabetes +anage+ent c T,e +i2 o* carbo,3drate, .rotein, and *at +a3 be adjusted to +eet t,e +eta/ bolic goals and indi0idual .re*erences o* t,e .erson 4it, diabetes. 7C9 c onitoring carbo,3drate, 4,et,er b3 carbo,3drate counting, c,oices, or e2/ .erience/based esti+ation, re+ains a 1e3 strateg3 in ac,ie0ing gl3ce+ic control. 7B9 c Saturated *at inta1e s,ould be ,FI o* total calories. 7B9 c Reducing inta1e o* trans *at lo4ers LDL

c,olesterol and increases DDL c,oles/ terol 7A9O t,ere*ore, inta1e o* trans *at s,ould be +ini+i;ed. 7E9

Ot,er nutrition reco++endations c I* adults 4it, diabetes c,oose to use alco,ol, t,e3 s,ould li+it inta1e to a +oderate a+ount 7one drin1 .er da3 or less *or adult 4o+en and t4o drin1s .er da3 or less *or adult +en9 and s,ould ta1e e2tra .recautions to .re0ent ,3.o/ gl3ce+ia. 7E9 c Routine su..le+entation 4it, anti/ o2idants, suc, as 0ita+ins E and C and carotene, is not ad0ised because o* lac1 o* e0idence o* e*5cac3 and concern re/ lated to long/ter+ sa*et3. 7A9 c It is reco++ended t,at indi0iduali;ed +eal .lanning include o.ti+i;ation o* *ood c,oices to +eet reco++ended di/ etar3 allo4ance 7RDA9@dietar3 re*erence inta1e 7DRI9 *or all +icronutrients. 7E9 $T is an integral co+.onent o* di/ abetes .re0ention, +anage+ent, and sel*/ +anage+ent education. In addition to its role in .re0enting and controlling diabetes, t,e ADA recogni;es t,e i+.ortance o* nutrition as an essential co+.onent o* an o0erall ,ealt,3 li*est3le. A *ull re0ie4 o* t,e e0idence regarding nutrition in .re0enting and controlling diabetes and its co+.lica/ tions and additional nutrition/related rec/ o++endations can be *ound in t,e ADA .osition state+ent =$utrition Reco++en/ dations and Inter0entions *or Diabetes? 7%%:9, 4,ic, is being u.dated as o* ()%!. Ac,ie0ing nutrition/ related goals re-uires a coordinated tea+ e**ort t,at includes t,e ac/ ti0e in0ol0e+ent o* t,e .erson 4it, .redia/ betes or diabetes. Because o* t,e co+.le2it3 o* nutrition issues, it is reco++ended t,at a registered dietitian 4,o is 1no4ledgeable and s1illed in i+.le+enting nutrition t,era.3 into diabetes +anage+ent and education be t,e tea+ +e+ber 4,o .ro/ 0ides $T. Clinical trials@outco+e studies o* $T ,a0e re.orted decreases in A%C at !8" +ont,s ranging *ro+ ).(H to (.BI 4it, ,ig,er reductions seen in t3.e ( diabetes o* s,orter duration. ulti.le studies ,a0e de+onstrated sustained i+/ .ro0e+ents in A%C at %( +ont,s and lon/ ger 4,en a registered dietitian .ro0ided *ollo4/u. 0isits ranging *ro+ +ont,l3 to ! sessions .er 3ear 7%%H8%((9. Studies in nondiabetic indi0iduals suggest t,at $T reduces LDL c,olesterol b3 %H8(H +g@dL u. to %"I 7%(!9 and su..ort a role *or li*est3le +odi5cation in treating

,3.ertension 7%(!,%(:9. Alt,oug, t,e i+.ortance o* 4eig,t loss *or o0er4eig,t and obese indi0iduals is 4ell docu+ented, an o.ti+al +acronutrient distribution and dietar3 .attern o* 4eig,t

loss diets ,as not been establis,ed. A s3ste+atic re0ie4 o* E) 4eig,t loss studies o* J%/3ear duration de+onstrated t,at +oderate 4eig,t loss ac,ie0ed t,roug, diet alone, diet and e2ercise, and +eal re/ .lace+ents can be ac,ie0ed and +ain/ tained 7:.E8EI 4eig,t loss at %( +ont,s9 7%(H9. Bot, lo4/*at lo4/carbo,3drate and editerranean st3le eating .atterns ,a0e been s,o4n to .ro+ote 4eig,t loss 4it, si+ilar results a*ter % to ( 3ears o* *ollo4/ u. 7%("8%(B9. A +eta/anal3sis s,o4ed t,at at " +ont,s, lo4/carbo,3drate diets 4ere associated 4it, greater i+.ro0e+ents in trigl3ceride and DDL c,olesterol concen/ trations t,an lo4/*at dietsO ,o4e0er, LDL c,olesterol 4as signi5cantl3 ,ig,er on t,e lo4/carbo,3drate diets 7%!)9. Because o* t,e e**ects o* obesit3 on insulin resistance, 4eig,t loss is an i+/ .ortant t,era.eutic objecti0e *or o0er/ 4eig,t or obese indi0iduals 4,o are at ris1 *or diabetes 7%!%9. T,e +ulti*actorial intensi0e li*est3le inter0ention used in t,e D##, 4,ic, included reduced inta1e o* *at and calories, led to 4eig,t loss a0eraging FI at " +ont,s and +aintenance o* HI 4eig,t loss at ! 3ears, associated 4it, a HEI reduction in incidence o* t3.e ( di/ abetes 7(!9. An RCT loo1ing at ,ig,/ris1 indi0iduals in S.ain s,o4ed t,at t,e editerranean dietar3 .attern reduced t,e incidence o* diabetes in t,e absence o* 4eig,t loss b3 H(I co+.ared 4it, t,e lo4/*at control grou. 7%!(9. Alt,oug, our societ3 abounds 4it, e2a+.les o* ,ig,/calorie nutrient/.oor *oods, large increases in t,e consu+.tion o* SSBs ,a0e coincided 4it, t,e e.ide+ics o* obesit3 and t3.e ( diabetes. In a +eta/ anal3sis o* eig,t .ros.ecti0e co,ort stud/ ies 7n H !%),E%B9, a diet ,ig, in consu+./ tion o* SSBs 4as associated 4it, t,e de0elo.+ent o* t3.e ( diabetes 7n H %H,):!9. Indi0iduals in t,e ,ig,est 0ersus lo4est -uantile o* SSB inta1e ,ad a ("I greater ris1 o* de0elo.ing diabetes 7%!!9. 6or indi0iduals 4it, t3.e ( diabetes, studies ,a0e de+onstrated t,at +oderate 4eig,t loss 7HI o* bod3 4eig,t9 is associ/ ated 4it, decreased insulin resistance, i+/ .ro0ed +easures o* gl3ce+ia and li.e+ia, and reduced blood .ressure 7%!:9O longer/ ter+ studies 7JH( 4ee1s9 s,o4ed +i2ed e**ects on A%C in adults 4it, t3.e ( diabetes 7%!H8%!F9, and in so+e studies results 4ere con*ounded b3 .,ar+acological 4eig,t loss t,era.3. Loo1 ADEAD 7Action *or Dealt, in Diabetes9 is a large clinical trial designed to deter+ine 4,et,er long/ter+ 4eig,t loss 4ill i+.ro0e gl3ce+ia and .re/ 0ent cardio0ascular e0ents in subjects 4it,

t3.e ( diabetes. One/3ear results o* t,e in/ tensi0e li*est3le inter0ention in t,is trial s,o4 an a0erage E."I 4eig,t loss, signi5/ cant reduction o* A%C, and reduction in se0eral CVD ris1 *actors 7%!E9, 4it, bene5ts sustained at : 3ears 7%!B9. At t,e ti+e t,is article 4as going to .ress, t,e Loo1 ADEAD trial 4as ,alted earl3, a*ter %% 3ears o* *ol/ lo4/u., because t,ere 4as no signi5cant di**erence in t,e .ri+ar3 cardio0ascular outco+e bet4een t,e 4eig,t loss and stan/ dard care grou. 7,tt.>@@444.ni,.go0@ne4s@ ,ealt,@oct()%(@nidd1/%B.,t+9. ulti.le cardio0ascular ris1 *actors 4ere i+.ro0ed 4it, 4eig,t loss, and t,ose .artici.ants on a0erage 4ere on *e4er +edications to ac,ie0e t,ese i+.ro0e+ents. Alt,oug, nu+erous studies ,a0e at/ te+.ted to identi*3 t,e o.ti+al +i2 o* +acronutrients *or +eal .lans o* .eo.le 4it, diabetes, a recent s3ste+atic re0ie4 7%:)9 con5r+s t,at t,ere is no +ost e**ec/ ti0e +i2 t,at a..lies broadl3, and t,at +acronutrient .ro.ortions s,ould be indi/ 0iduali;ed. It +ust be clearl3 recogni;ed t,at regardless o* t,e +acronutrient +i2, total caloric inta1e +ust be a..ro.riate to 4eig,t +anage+ent goal. 6urt,er, indi0id/ uali;ation o* t,e +acronutrient co+.osi/ tion 4ill de.end on t,e +etabolic status o* t,e .atient 7e.g., li.id .ro5le, renal *unc/ tion9 and@or *ood .re*erences. A 0ariet3 o* dietar3 +eal .atterns are li1el3 e**ecti0e in +anaging diabetes including editerra/ nean/ st3le, .lant/based 70egan or 0egetar/ ian9, lo4/*at and lo4er/carbo,3drate eating .atterns 7%(F,%:%8%:!9. It s,ould be noted t,at t,e RDA *or digestible carbo,3drate is %!) g@da3 and is based on .ro0iding ade-uate glucose as t,e re-uired *uel *or t,e central ner0ous s3ste+ 4it,out reliance on glucose .roduction *ro+ ingested .rotein or *at. Alt,oug, brain *uel needs can be +et on lo4er carbo,3drate diets, long/ter+ +etabolic e**ects o* 0er3 lo4/carbo,3drate diets are unclear and suc, diets eli+inate +an3 *oods t,at are i+.ortant sources o* energ3, 5ber, 0ita+ins, and +inerals and are i+/ .ortant in dietar3 .alatabilit3 7%::9. Saturated and trans *att3 acids are t,e .rinci.al dietar3 deter+inants o* .las+a LDL c,olesterol. T,ere is a lac1 o* e0i/ dence on t,e e**ects o* s.eci5c *att3 acids on .eo.le 4it, diabetes, so t,e reco+/ +ended goals are consistent 4it, t,ose *or indi0iduals 4it, CVD 7%(!,%:H9. Rei+burse+ent *or $T $T, 4,en deli0ered b3 a registered

dietitian according to nutrition .ractice guidelines, is rei+bursed as .art o* t,e

edicare .rogra+ as o0erseen b3 t,e Centers *or edicare and edicaid Ser0/ ices 7C S9, as 4ell as +an3 ,ealt, in/ surance .lans. 6. Diabetes sel*/+anage+ent education and su..ort Reco++endations c #eo.le 4it, diabetes s,ould recei0e DS E and diabetes sel*/+anage+ent su..ort 7DS S9 according to $ational Standards *or Diabetes Sel*/ anage/ +ent Education and Su..ort 4,en t,eir diabetes is diagnosed and as needed t,erea*ter. 7B9 c E**ecti0e sel*/+anage+ent and -ualit3 o* li*e are t,e 1e3 outco+es o* DS E and DS S and s,ould be +easured and +onitored as .art o* care. 7C9 c DS E and DS S s,ould address .s3c,osocial issues, since e+otional 4ell/being is associated 4it, .ositi0e diabetes outco+es. 7C9 c DS E and DS S .rogra+s are a..ro/ .riate 0enues *or .eo.le 4it, .rediabetes to recei0e education and su..ort to de/ 0elo. and +aintain be,a0iors t,at can .re0ent or dela3 t,e onset o* diabetes. 7C9 c Because DS E and DS S can result in cost/sa0ings and i+.ro0ed outco+es 7B9, DS E and DS S s,ould be ade-uatel3 rei+bursed b3 t,ird/.art3 .a3ers. 7E9 DS E and DS S are essential ele/ +ents o* diabetes care 7%:"8%H%9, and re/ centl3 u.dated $ational Standards *or Diabetes Sel*/ anage+ent Education and Su..ort 7%H(9 are based on e0idence *or its bene5ts. Education ,el.s .eo.le 4it, dia/ betes initiate e**ecti0e sel*/ +anage+ent and co.e 4it, diabetes 4,en t,e3 are 5rst di/ agnosed. Ongoing DS E and DS S also ,el. .eo.le 4it, diabetes +aintain e**ec/ ti0e sel*/ +anage+ent t,roug,out a li*eti+e o* diabetes as t,e3 *ace ne4 c,allenges and treat+ent ad0ances beco+e a0ailable. DS E ,el.s .atients o.ti+i;e +etabolic control, .re0ent and +anage co+.lica/ tions, and +a2i+i;e -ualit3 o* li*e in a cost/e**ecti0e +anner 7%H!9. DS E and DS S are t,e ongoing .rocesses o* *acilitating t,e 1no4ledge, s1ill, and abilit3 necessar3 *or diabetes sel*/care. T,is .rocess incor.orates t,e needs, goals, and li*e e2.eriences o* t,e .erson 4it, diabetes. T,e o0erall objec/ ti0es o* DS E and DS S are to su..ort in*or+ed decision +a1ing, sel*/care be,a0/ iors, .roble+/sol0ing, and acti0e

collabo/ ration 4it, t,e ,ealt, care tea+ to i+.ro0e clinical outco+es, ,ealt, status, and -ual/ it3 o* li*e in a cost/e**ecti0e +anner 7%H(9.

Current best .ractice o* DS E is a s1ill/based a..roac, t,at *ocuses on ,el.ing t,ose 4it, diabetes +a1e in/ *or+ed sel*/+anage+ent c,oices. DS E ,as c,anged *ro+ a didactic a..roac, *ocusing on .ro0iding in*or+ation to +ore t,eoreticall3 based e+.o4er+ent +odels t,at *ocus on ,el.ing t,ose 4it, diabetes +a1e in*or+ed sel*/+anage+ent decisions. Care o* diabetes ,as s,i*ted to an a..roac, t,at is +ore .atient centered and .laces t,e .erson 4it, diabetes and ,is or ,er *a+il3 at t,e center o* t,e care +odel 4or1ing in collaboration 4it, ,ealt, care .ro*essionals. #atient/ centered care is res.ect*ul o* and res.on/ si0e to indi0idual .atient .re*erences, needs, and 0alues and ensures t,at .atient 0alues guide all decision +a1ing 7%H:9. E0idence *or t,e bene5ts o* DS E and DS S ulti.le studies ,a0e *ound t,at DS E is associated 4it, i+.ro0ed diabetes 1no4l/ edge and i+.ro0ed sel*/care be,a0ior 7%:"9, i+.ro0ed clinical outco+es suc, as lo4er A%C 7%:F,%:E,%H),%H%,%HH8 %HE9, lo4er sel*/re.orted 4eig,t 7%:"9, i+/ .ro0ed -ualit3 o* li*e 7%:B,%H",%HB9, ,ealt,3 co.ing 7%")9, and lo4er costs 7%"%9. Better outco+es 4ere re.orted *or DS E inter0entions t,at 4ere longer and included *ollo4/u. su..ort 7DS S9 7%:",%"(8%"H9, t,at 4ere cultural l3 7%"",%"F9 and age a..ro.riate 7%"E,%"B9 and 4ere tailored to indi0idual needs and .re*erences, and t,at addressed .s3c,oso/ cial issues and incor.orated be,a0ioral strategies 7%:",%H),%F),%F%9. Bot, indi/ 0idual and grou. a..roac,es ,a0e been *ound e**ecti0e 7%F(,%F!9. T,ere is gro4ing e0idence *or t,e role o* co++unit3 ,ealt, 4or1ers and .eer 7%F:8%E)9 and la3 lead/ ers 7%E%9 in deli0ering DS E and DS S in conjunction 4it, t,e core tea+ 7%E(9. Diabetes education is associated 4it, increased use o* .ri+ar3 and .re0enti0e ser0ices 7%"%,%E!9 and lo4er use o* acute, in.atient ,os.ital ser0ices 7%"%9. #atients 4,o .artici.ate in diabetes education are +ore li1el3 to *ollo4 best .ractice treat/ +ent reco++endations, .articularl3 a+ong t,e edicare .o.ulation, and ,a0e lo4er edicare and co++ercial clai+ costs 7%E:,%EH9. T,e $ational Standards *or Diabetes Sel*/ anage+ent Education and Su..ort T,e $ational Standards *or Diabetes Sel*/ anage+ent Education and Su..ort are designed to de5ne -ualit3 DS E and

DS S and to assist diabetes educators in a 0ariet3 o* settings to .ro0ide e0idence/ based education and sel*/ +anage+ent su..ort 7%H(9. T,e standards, recentl3 u./ dated, are re0ie4ed and u.dated e0er3 H 3ears b3 a tas1 *orce re.resenting 1e3 or/ gani;ations in0ol0ed in t,e 5eld o* diabetes education and care. DS E and DS S .ro0iders and .eo/ .le 4it, .rediabetes T,e ne4 standards *or DS E and DS S also a..l3 to t,e education and su..ort o* .eo.le 4it, .rediabetes. Currentl3, t,ere are signi5cant barriers to t,e .ro0ision o* education and su..ort to t,ose 4it, .re/ diabetes. Do4e0er, t,e strategies *or su./ .orting success*ul be,a0ior c,ange and t,e ,ealt,3 be,a0iors reco++ended *or .eo.le 4it, .rediabetes are largel3 iden/ tical to t,ose *or .eo.le 4it, diabetes. As barriers to care are o0erco+e, .ro0iders o* DS E and DS S, gi0en t,eir training and e2.erience, are .articularl3 4ell e-ui..ed to assist .eo.le 4it, .rediabetes in de/ 0elo.ing and +aintaining be,a0iors t,at can .re0ent or dela3 t,e onset o* diabetes 7%H(,%E"9. Rei+burse+ent *or DS E and DS S DS E, 4,en .ro0ided b3 a .rogra+ t,at +eets national standards *or DS E and is recogni;ed b3 t,e ADA or ot,er a..ro0al bodies, is rei+bursed as .art o* t,e edicare .rogra+ as o0erseen b3 t,e C S. DS E is also co0ered b3 +ost ,ealt, insurance .lans. Alt,oug, DS S ,as been s,o4n to be instru+ental *or i+.ro0ing outco+es, as described in t,e =E0idence *or t,e bene5ts o* DS E and DS S,? and can be .ro0ided in *or+ats suc, as .,one calls and 0ia tele/ ,ealt,, it currentl3 ,as li+ited rei+burse/ +ent as *ace/to/*ace 0isits included as *ollo4/u. to DS E. C. #,3sical acti0it3 Reco++endations c Adults 4it, diabetes s,ould be ad0ised to .er*or+ at least %H) +in@4ee1 o* +oderate/intensit3 aerobic .,3sical acti0it3 7H)8F)I o* +a2i+u+ ,eart rate9, s.read o0er at least ! da3s@4ee1 4it, no +ore t,an t4o consecuti0e da3s 4it,out e2ercise. 7A9 c In t,e absence o* contraindications, adults 4it, t3.e ( diabetes s,ould be encouraged to .er*or+ resistance train/ ing at least t4ice .er 4ee1. 7A9 E2ercise is an i+.ortant .art o* t,e

diabetes +anage+ent .lan. Regular e2er/ cise ,as been s,o4n to i+.ro0e blood

glucose control, reduce cardio0ascular ris1 *actors, contribute to 4eig,t loss, and i+.ro0e 4ell/being. 6urt,er+ore, regular e2ercise +a3 .re0ent t3.e ( diabetes in ,ig,/ris1 indi0iduals 7(!8 (H9. Structured e2ercise inter0entions o* at least E 4ee1s< duration ,a0e been s,o4n to lo4er A%C b3 an a0erage o* ).""I in .eo.le 4it, t3.e ( diabetes, e0en 4it, no signi5cant c,ange in B I 7%EF9. Dig,er le0els o* e2ercise in/ tensit3 are associated 4it, greater i+.ro0e/ +ents in A%C and in 5tness 7%EE9. A joint .osition state+ent o* t,e ADA and t,e A+erican College o* S.orts edicine 7ACS 9 su++ari;es t,e e0idence *or t,e bene5ts o* e2ercise in .eo.le 4it, t3.e ( diabetes 7%EB9. 6re-uenc3 and t3.e o* e2ercise T,e U.S. De.art+ent o* Dealt, and Du+an Ser0ices< #,3sical Acti0it3 Cuidelines *or A+ericans 7%B)9 suggest t,at adults o0er age %E 3ears do %H) +in@4ee1 o* +oder/ ate/intensit3, or FH +in@4ee1 o* 0igorous aerobic .,3sical acti0it3, or an e-ui0alent co+bination o* t,e t4o. In addition, t,e guidelines suggest t,at adults also do +uscle/strengt,ening acti0ities t,at in/ 0ol0e all +ajor +uscle grou.s J( da3s@ 4ee1. T,e guidelines suggest t,at adults o0er age "H 3ears, or t,ose 4it, disabili/ ties, *ollo4 t,e adult guidelines i* .ossible or 7i* t,is is not .ossible9 be as .,3sicall3 acti0e as t,e3 are able. Studies included in t,e +eta/anal3sis o* e**ects o* e2ercise in/ ter0entions on gl3ce+ic control 7%EF9 ,ad a +ean nu+ber o* sessions .er 4ee1 o* !.:, 4it, a +ean o* :B +in .er session. T,e D## li*est3le inter0ention, 4,ic, included %H) +in@4ee1 o* +oder/ ate/intensit3 e2ercise, ,ad a bene5cial e**ect on gl3ce+ia in t,ose 4it, .redia/ betes. T,ere*ore, it see+s reasonable to reco++end t,at .eo.le 4it, diabetes tr3 to *ollo4 t,e .,3sical acti0it3 guide/ lines *or t,e general .o.ulation. #rogressi0e resistance e2ercise i+/ .ro0es insulin sensiti0it3 in older +en 4it, t3.e ( diabetes to t,e sa+e or e0en a greater e2tent as aerobic e2ercise 7%B%9. Clinical trials ,a0e .ro0ided strong e0idence *or t,e A%C lo4ering 0alue o* resistance training in older adults 4it, t3.e ( dia/ betes 7%B(,%B!9 and *or an additi0e ben/ e5t o* co+bined aerobic and resistance

e2ercise in adults 4it, t3.e ( diabetes 7%B:,%BH9. In t,e absence o* contraindi/ cations, .atients 4it, t3.e ( diabetes s,ould be encouraged to do at least t4o 4ee1l3 sessions o* resistance e2ercise 7e2/ ercise 4it, *ree 4eig,ts or 4eig,t +a/ c,ines9, 4it, eac, session consisting o*

at least one set o* 50e or +ore di**erent resistance e2ercises in0ol0ing t,e large +uscle grou.s 7%EB9. E0aluation o* t,e diabetic .atient be*ore reco++ending an e2ercise .rogra+ #rior guidelines suggested t,at be*ore reco++ending a .rogra+ o* .,3sical acti0/ it3, t,e .ro0ider s,ould assess .atients 4it, +ulti.le cardio0ascular ris1 *actors *or cor/ onar3 arter3 disease 7CAD9. As discussed +ore *ull3 in Section VI.A.H, t,e area o* screening as3+.to+atic diabetic .atients *or CAD re+ains unclear, and a recent ADA consensus state+ent on t,is issue con/ cluded t,at routine screening is not reco+/ +ended 7%B"9. #ro0iders s,ould use clinical judg+ent in t,is area. Certainl3, ,ig,/ris1 .atients s,ould be encouraged to start 4it, s,ort .eriods o* lo4/intensit3 e2ercise and increase t,e intensit3 and duration slo4l3. #ro0iders s,ould assess .atients *or conditions t,at +ig,t contraindicate cer/ tain t3.es o* e2ercise or .redis.ose to injur3, suc, as uncontrolled ,3.erten/ sion, se0ere autono+ic neuro.at,3, se/ 0ere .eri.,eral neuro.at,3 or ,istor3 o* *oot lesions, and unstable .roli*erati0e retino.at,3. T,e .atient<s age and .re/ 0ious .,3sical acti0it3 le0el s,ould be considered. E2ercise in t,e .resence o* nono.ti+al gl3ce+ic control D3.ergl3ce+ia. K,en .eo.le 4it, t3.e % diabetes are de.ri0ed o* insulin *or %(8 :E , and are 1etotic, e2ercise can 4orsen ,3.ergl3ce+ia and 1etosis 7%BF9O t,ere/ *ore, 0igorous acti0it3 s,ould be a0oided in t,e .resence o* 1etosis. Do4e0er, it is not necessar3 to .ost.one e2ercise based si+.l3 on ,3.ergl3ce+ia, .ro0ided t,e .atient *eels 4ell and urine and@or blood 1etones are negati0e. D3.ogl3ce+ia. In indi0iduals ta1ing in/ sulin and@or insulin secretagogues, .,3s/ ical acti0it3 can cause ,3.ogl3ce+ia i* +edication dose or carbo,3drate con/ su+.tion is not altered. 6or indi0iduals on t,ese t,era.ies, added carbo,3drate s,ould be ingested i* .re/e2ercise glucose le0els are ,%)) +g@dL 7H." ++ol@L9. D3/ .ogl3ce+ia is rare in diabetic indi0iduals 4,o are not treated 4it, insulin or insulin secretagogues, and no .re0enti0e +ea/ sures *or ,3.ogl3ce+ia are usuall3 ad/ 0ised in t,ese cases. E2ercise in t,e .resence o* s.eci5c long/ter+ co+.lications o* diabetes Retino.at,3. In t,e .resence o* .roli*er/ ati0e diabetic retino.at,3 7#DR9 or se0ere

non/#DR 7$#DR9, 0igorous aerobic or resistance e2ercise +a3 be contraindi/ cated because o* t,e ris1 o* triggering 0itreous ,e+orr,age or retinal detac,/ +ent 7%BE9. #eri.,eral neuro.at,3. Decreased .ain sensation in t,e e2tre+ities results in increased ris1 o* s1in brea1do4n and in*ection and o* C,arcot joint destruc/ tion. #rior reco++endations ,a0e ad/ 0ised non84eig,t/bearing e2ercise *or .atients 4it, se0ere .eri.,eral neuro.a/ t,3. Do4e0er, studies ,a0e s,o4n t,at +oderate/intensit3 4al1ing +a3 not lead to increased ris1 o* *oot ulcers or reulceration in t,ose 4it, .eri.,eral neuro.at,3 7%BB9. All indi0iduals 4it, .eri.,eral neuro.at,3 s,ould 4ear .ro.er *oot4ear and e2a+ine t,eir *eet dail3 to detect lesions earl3. An3one 4it, a *oot injur3 or o.en sore s,ould be restricted to non84eig,t/bearing ac/ ti0ities. Autono+ic neuro.at,3. Autono+ic neu/ ro.at,3 can increase t,e ris1 o* e2ercise/ induced injur3 or ad0erse e0ent t,roug, decreased cardiac res.onsi0eness to e2er/ cise, .ostural ,3.otension, i+.aired t,er/ +oregulation, i+.aired nig,t 0ision due to i+.aired .a.illar3 reaction, and un.redict/ able carbo,3drate deli0er3 *ro+ gastro.a/ resis .redis.osing to ,3.ogl3ce+ia 7())9. Autono+ic neuro.at,3 is also strongl3 as/ sociated 4it, CVD in .eo.le 4it, diabetes 7()%,()(9. #eo.le 4it, diabetic autono+ic neuro.at,3 s,ould undergo cardiac in0es/ tigation be*ore beginning .,3sical acti0it3 +ore intense t,an t,at to 4,ic, t,e3 are accusto+ed. Albu+inuria and ne.,ro.at,3. #,3sical acti0it3 can acutel3 increase urinar3 .ro/ tein e2cretion. Do4e0er, t,ere is no e0i/ dence t,at 0igorous e2ercise increases t,e rate o* .rogression o* diabetic 1idne3 disease, and t,ere is li1el3 no need *or an3 s.eci5c e2ercise restrictions *or .eo/ .le 4it, diabetic 1idne3 disease 7()!9. D. #s3c,osocial assess+ent and care Reco++endations c It is reasonable to include assess+ent o* t,e .atient<s .s3c,ological and social situation as an ongoing .art o* t,e +edical +anage+ent o* diabetes. 7E9 c #s3c,osocial screening and *ollo4/u. +a3 include, but is not li+ited to, at/ titudes about t,e illness, e2.ectations *or +edical +anage+ent and out/ co+es, a**ect@+ood, general and di/

abetes/related -ualit3 o* li*e, resources 75nancial, social, and e+otional9, and .s3c,iatric ,istor3. 7E9

Screen *or .s3c,osocial .roble+s suc, as de.ression and diabetes/related distress, an2iet3, eating disorders, and cogniti0e i+.air+ent 4,en sel*/ +anage+ent is .oor. 7B9

de.ression9, indications o* an eating disorder 7(%E9, or cogniti0e *unctioning t,at signi5cantl3 i+.airs judg+ent. It is .re*erable to

It is i+.ortant to establis, t,at e+otional 4ell/being is .art o* diabetes care and sel*/ +anage+ent. #s3c,ological and social .roble+s can i+.air t,e indi0idual<s 7():8()F9 or *a+il3<s abilit3 to carr3 out diabetes care tas1s and t,ere*ore co+.ro/ +ise ,ealt, status. T,ere are o..ortuni/ ties *or t,e clinician to assess .s3c,osocial status in a ti+el3 and e*5cient +anner so t,at re*erral *or a..ro.riate ser0ices can be acco+.lis,ed. A s3ste+atic re0ie4 and +eta/anal3sis s,o4ed t,at .s3c,osocial inter0entions +odestl3 but signi5cantl3 i+.ro0ed A%C 7standardi;ed +ean di**er/ ence ().(BI9 and +ental ,ealt, out/ co+es. Do4e0er, t,ere 4as a li+ited association bet4een t,e e**ects on A%C and +ental ,ealt,, and no inter0ention c,aracteristics .redicted bene5t on bot, outco+es 7()E9. Qe3 o..ortunities *or screening o* .s3c,osocial status occur at diagnosis, during regularl3 sc,eduled +anage+ent 0isits, during ,os.itali;ations, at disco0/ er3 o* co+.lications, or 4,en .roble+s 4it, glucose control, -ualit3 o* li*e, or ad,erence are identi5ed. #atients are li1el3 to e2,ibit .s3c,ological 0ulnerabil/ it3 at diagnosis and 4,en t,eir +edical status c,anges 7e.g., t,e end o* t,e ,on/ e3+oon .eriod9, 4,en t,e need *or in/ tensi5ed treat+ent is e0ident, and 4,en co+.lications are disco0ered 7()"9. De.ression a**ects about ()8(HI o* .eo.le 4it, diabetes 7()F9 and increases t,e ris1 *or I and .ost/ I 7()B,(%)9 and all/cause 7(%%9 +ortalit3. Ot,er issues 1no4n to i+.act sel*/ +anage+ent and ,ealt, outco+es include but are not li+ited to attitudes about t,e illness, e2.ectations *or +edical +anage+ent and outco+es, a**ect@+ood, general and diabetes/ related -ualit3 o* li*e, diabetes/related distress 7(%(,(%!9, resources 75nancial, social, and e+otional9 7(%:9, and .s3c,iatric ,is/ tor3 7(%H8(%F9. Screening tools are a0ail/ able *or a nu+ber o* t,ese areas 7%F)9. Indications *or re*erral to a +ental ,ealt, s.ecialist *a+iliar 4it, diabetes +anage/ +ent +a3 include gross disregard *or t,e +edical regi+en 7b3 sel* or ot,ers9 7(%F9, de.ression, .ossibilit3 o* sel*/,ar+, debil/ itating an2iet3 7alone or 4it,

incor.orate .s3c,ological assess+ent and treat+ent into routine care rat,er t,an 4aiting *or identi5cation o* a s.eci5c .roble+ or deterioration in .s3c,ological status 7%F)9. Alt,oug, t,e clinician +a3 not *eel -uali5ed to treat .s3c,ological .roble+s 7(%B9, utili;ing t,e .atient/ .ro0ider relations,i. as a *oundation can increase t,e li1eli,ood t,at t,e .a/ tient 4ill acce.t re*erral *or ot,er ser0ices. Collaborati0e care inter0entions and using a tea+ a..roac, ,a0e de+on/ strated e*5cac3 in diabetes and de.res/ sion 7((),((%9. I. K,en treat+ent goals are not +et 6or a 0ariet3 o* reasons, so+e .eo.le 4it, diabetes and t,eir ,ealt, care .ro0iders do not ac,ie0e t,e desired goals o* treat/ +ent 7Table B9. Ret,in1ing t,e treat+ent regi+en +a3 re-uire assess+ent o* barri/ ers including inco+e, ,ealt, literac3, diabetes distress, de.ression, and co+/ .eting de+ands, including t,ose related to *a+il3 res.onsibilities and d3na+ics. Ot,er strategies +a3 include culturall3 a..ro.riate and en,anced DS E and DS S, co/+anage+ent 4it, a diabetes tea+, re*erral to a +edical social 4or1er *or assistance 4it, insurance co0erage, or c,ange in .,ar+acological t,era.3. Initi/ ation o* or increase in S BC, utili;ation o* CC , *re-uent contact 4it, t,e .a/ tient, or re*erral to a +ental ,ealt, .ro/ *essional or .,3sician 4it, s.ecial e2.ertise in diabetes +a3 be use*ul. &. Intercurrent illness T,e stress o* illness, trau+a, and@or sur/ ger3 *re-uentl3 aggra0ates gl3ce+ic con/ trol and +a3 .reci.itate diabetic 1etoacidosis 7DQA9 or non1etotic ,3.er/ os+olar statedli*e/t,reatening conditions t,at re-uire i++ediate +edical care to .re/ 0ent co+.lications and deat,. An3 condi/ tion leading to deterioration in gl3ce+ic control necessitates +ore *re-uent +onitor/ ing o* blood glucose and 7in 1etosis/.rone .atients9 urine or blood 1etones. ar1ed ,3.ergl3ce+ia re-uires te+.orar3 adjust/ +ent o* t,e treat+ent .rogra+ and, i* ac/ co+.anied b3 1etosis, 0o+iting, or alteration in le0el o* consciousness, i++e/ diate interaction 4it, t,e diabetes care tea+. T,e .atient treated 4it, noninsulin t,era.ies or $T alone +a3 te+.oraril3 re-uire insulin. Ade-uate Auid and caloric inta1e +ust be assured. In*ection or de,3/ dration is +ore li1el3 to necessitate ,os.i/ tali;ation o* t,e .erson 4it, diabetes t,an t,e .erson 4it,out diabetes.

T,e ,os.itali;ed .atient s,ould be treated b3 a .,3sician 4it, e2.ertise in t,e +anage+ent o* diabetes. 6or *urt,er in*or+ation on +anage+ent o* .atients 4it, ,3.ergl3ce+ia in t,e ,os.ital, see Section IU.A. 6or *urt,er in*or+ation on +anage+ent o* DQA or ,3.ergl3ce+ic non1etotic ,3.eros+olar state, re*er to t,e ADA state+ent on ,3.ergl3ce+ic crises 7(((9. Q. D3.ogl3ce+ia Reco++endations c Indi0iduals at ris1 *or ,3.ogl3ce+ia s,ould be as1ed about s3+.to+atic and as3+.to+atic ,3.ogl3ce+ia at eac, encounter. 7C9 c Clucose 7%H8() g9 is t,e .re*erred treat+ent *or t,e conscious indi0idual 4it, ,3.ogl3ce+ia, alt,oug, an3 *or+ o* carbo,3drate t,at contains glucose +a3 be used. I* S BC %H +in a*ter treat+ent s,o4s continued ,3.ogl3/ ce+ia, t,e treat+ent s,ould be re/ .eated. Once S BC glucose returns to nor+al, t,e indi0idual s,ould consu+e a +eal or snac1 to .re0ent recurrence o* ,3.ogl3ce+ia. 7E9 c Clucagon s,ould be .rescribed *or all indi0iduals at signi5cant ris1 o* se0ere ,3.ogl3ce+ia, and caregi0ers or *a+il3 +e+bers o* t,ese indi0iduals s,ould be instructed on its ad+inistration. Clucagon ad+inistration is not li+ited to ,ealt, care .ro*essionals. 7E9 c D3.ogl3ce+ia una4areness or one or +ore e.isodes o* se0ere ,3.ogl3ce+ia s,ould trigger re/e0aluation o* t,e treat+ent regi+en. 7E9 c Insulin/treated .atients 4it, ,3.ogl3/ ce+ia una4areness or an e.isode o* se0ere ,3.ogl3ce+ia s,ould be ad0ised to raise t,eir gl3ce+ic targets to strictl3 a0oid *urt,er ,3.ogl3ce+ia *or at least se0eral 4ee1s, to .artiall3 re0erse ,3/ .ogl3ce+ia una4areness, and to re/ duce ris1 o* *uture e.isodes. 7A9 c Ongoing assess+ent o* cogniti0e *unc/ tion is suggested 4it, increased 0igilance *or ,3.ogl3ce+ia b3 t,e clinician, .a/ tient, and caregi0ers i* lo4 cognition and@or declining cognition is *ound. 7B9 D3.ogl3ce+ia is t,e leading li+iting *actor in t,e gl3ce+ic +anage+ent o* t3.e % and insulin/treated t3.e ( diabetes 7((!9.

ild ,3.ogl3ce+ia +a3 be incon0enient or *rig,tening to .atients 4it, diabetes, and +ore se0ere ,3.ogl3ce+ia can cause acute ,ar+ to t,e .erson 4it, diabetes or ot,ers, i* it causes *alls, +otor 0e,icle

accidents, or ot,er injur3. A large co,ort stud3 suggested t,at a+ong older adults 4it, t3.e ( diabetes, a ,istor3 o* se0ere ,3.ogl3ce+ia 4as associated 4it, greater ris1 o* de+entia 7((:9. Con0ersel3, in a substud3 o* t,e ACCORD trial, cogniti0e i+.air+ent at baseline or decline in cog/ niti0e *unction during t,e trial 4as signi*/ icantl3 associated 4it, subse-uent e.isodes o* se0ere ,3.ogl3ce+ia 7((H9. E0idence *ro+ t,e DCCT@EDIC trial, 4,ic, in0ol0ed 3ounger adults and ado/ lescents 4it, t3.e % diabetes, suggested no association o* *re-uenc3 o* se0ere ,3.o/ gl3ce+ia 4it, cogniti0e decline 7(("9. As discussed in t,e Section VIII.A.%.a, a *e4 studies ,a0e suggested t,at se0ere ,3.o/ gl3ce+ia in 0er3 3oung c,ildren is associ/ ated 4it, +ild i+.air+ents in cogniti0e *unction. As described in t,e Section V.b.(, se0ere ,3.ogl3ce+ia 4as associated 4it, +ortalit3 in .artici.ants in bot, t,e stan/ dard and intensi0e gl3ce+ia ar+s o* t,e ACCORD trial, but t,e relations,i.s 4it, ac,ie0ed A%C and treat+ent intensit3 4ere not straig,t*or4ard. An association o* se0ere ,3.ogl3ce+ia 4it, +ortalit3 4as also *ound in t,e ADVA$CE trial 7((F9, but its association 4it, ot,er out/ co+es suc, as .ul+onar3 and s1in disor/ ders raises t,e -uestion o* 4,et,er se0ere ,3.ogl3ce+ia is a +ar1er *or a sic1er .a/ tient, rat,er t,an a cause o* +ortalit3. An association o* sel*/re.orted se0ere ,3.o/ gl3ce+ia 4it, H/3ear +ortalit3 ,as also been re.orted in clinical .ractice 7((E9. At t,e ti+e t,is state+ent 4ent to .ress, t,e ADA and T,e Endocrine Societ3 4ere 5nali;ing a D3.ogl3ce+ia Kor1 Crou. re.ort, 4,ere t,e causes o* and associa/ tions 4it, ,3.ogl3ce+ia are discussed in de.t,. Treat+ent o* ,3.ogl3ce+ia 7.las+a glucose ,F) +g@dL9 re-uires ingestion o* glucose/ or carbo,3drate/containing *oods. T,e acute gl3ce+ic res.onse cor/ relates better 4it, t,e glucose content t,an 4it, t,e carbo,3drate content o* t,e *ood. Alt,oug, .ure glucose is t,e .re*erred treat+ent, an3 *or+ o* carbo,3/ drate t,at contains glucose 4ill raise blood glucose. Added *at +a3 retard and t,en .rolong t,e acute gl3ce+ic res.onse. Ongoing acti0it3 o* insulin or insulin sec/ retagogues +a3 lead to recurrence o* ,3.o/ gl3ce+ia unless *urt,er *ood is ingested

a*ter reco0er3. Se0ere ,3.ogl3ce+ia 74,ere t,e in/ di0idual re-uires t,e assistance o* an/ ot,er .erson and cannot be treated 4it, oral carbo,3drate due to con*usion or

unconsciousness9 s,ould be treated using e+ergenc3 glucagon 1its, 4,ic, re-uire a .rescri.tion. T,ose in close contact 4it,, or ,a0ing custodial care o*, .eo.le 4it, ,3.ogl3ce+ia/.rone diabetes 7*a+il3 +e+bers, roo++ates, sc,ool .ersonnel, c,ild care .ro0iders, correctional institu/ tion sta**, or co4or1ers9 s,ould be in/ structed in use o* suc, 1its. An indi0idual does not need to be a ,ealt, care .ro/ *essional to sa*el3 ad+inister glucagon. Care s,ould be ta1en to ensure t,at un/ e2.ired glucagon 1its are a0ailable. #re0ention o* ,3.ogl3ce+ia is a crit/ ical co+.onent o* diabetes +anage+ent. #articularl3 *or insulin/treated .atients, S BC and, *or so+e .atients, CC to detect inci.ient ,3.ogl3ce+ia and assess ade-uac3 o* treat+ent are a 1e3 co+.o/ nent o* sa*e t,era.3. #atients s,ould un/ derstand situations t,at increase t,eir ris1 o* ,3.ogl3ce+ia, suc, as 4,en *asting *or tests or .rocedures, during or a*ter in/ tense e2ercise, and during slee. and t,at increase t,e ris1 o* ,ar+ to sel* or ot,ers *ro+ ,3.ogl3ce+ia, suc, as 4it, dri0ing. Teac,ing .eo.le 4it, diabetes to balance insulin use, carbo,3drate inta1e, and e2ercise is a necessar3 but not al4a3s su*5cient strateg3 *or .re0ention. In t3.e % diabetes and se0erel3 insulin/de5cient t3.e ( diabetes, t,e s3ndro+e o* ,3.o/ gl3ce+ia una4areness, or ,3.ogl3ce+ia/ associated autono+ic *ailure, can se0erel3 co+.ro+ise stringent diabetes control and -ualit3 o* li*e. T,e de5cient counter/ regulator3 ,or+one release and autono+ic res.onses in t,is s3ndro+e are bot, ris1 *actors *or, and caused b3, ,3.ogl3ce+ia. A corollar3 to t,is =0icious c3cle? is t,at se0/ eral 4ee1s o* a0oidance o* ,3.ogl3ce+ia ,as been de+onstrated to i+.ro0e counter/regulation and a4areness to so+e e2tent in +an3 .atients 7((B9. Dence, .atients 4it, one or +ore e.isodes o* se0ere ,3.ogl3ce+ia +a3 bene5t *ro+ at least s,ort/ter+ rela2ation o* gl3ce+ic targets. L. Bariatric surger3 Reco++endations c Bariatric surger3 +a3 be considered *or ( adults 4it, B I J!H 1g@+ and t3.e ( diabetes, es.eciall3 i* t,e diabetes or associated co+orbidities are di*5cult to control 4it, li*est3le and .,ar+aco/ logical t,era.3. 7B9 c #atients 4it, t3.e ( diabetes 4,o ,a0e undergone bariatric surger3 need li*e/ long li*est3le su..ort and +edical +onitoring. 7B9

Alt,oug, s+all trials ,a0e s,o4n gl3/ ce+ic bene5t o* bariatric surger3 in .atients 4it, t3.e ( diabetes and B I ( !)8!H 1g@+ , t,ere is currentl3 in/ su*5cient e0idence to generall3 rec/ o++end surger3 in .atients 4it, B I ( ,!H 1g@+ outside o* a researc, .ro/ tocol. 7E9 c T,e long/ter+ bene5ts, cost/ e**ecti0eness, and ris1s o* bariatric surger3 in indi0i/ duals 4it, t3.e ( diabetes s,ould be studied in 4ell/designed controlled trials 4it, o.ti+al +edical and li*est3le t,era.3 as t,e co+.arator. 7E9
c

Castric reduction surger3, eit,er gas/ tric banding or .rocedures t,at in0ol0e b3.assing, trans.osing, or resecting sec/ tions o* t,e s+all intestine, 4,en .art o* a co+.re,ensi0e tea+ a..roac,, can be an e**ecti0e 4eig,t loss treat+ent *or se0ere obesit3, and national guidelines su..ort its consideration *or .eo.le 4it, t3.e ( ( diabetes 4,o ,a0e B I o* !H 1g@+ or greater. Bariatric surger3 ,as been s,o4n to lead to near/ or co+.lete nor/ +ali;ation o* gl3ce+ia in O:)8BHI o* .atients 4it, t3.e ( diabetes, de.ending on t,e stud3 and t,e surgical .rocedure 7(!)8(!(9. A +eta/anal3sis o* studies o* bariatric surger3 in0ol0ing !,%EE .atients 4it, diabetes re.orted t,at FEI ,ad re/ +ission o* diabetes 7nor+ali;ation o* blood glucose le0els in t,e absence o* +edications9 and t,at t,e re+ission rates 4ere sustained in studies t,at ,ad *ollo4/ u. e2ceeding ( 3ears 7(!!9. Re+ission rates tend to be lo4er 4it, .rocedures t,at onl3 constrict t,e sto+ac, and ,ig,er 4it, t,ose t,at b3.ass .ortions o* t,e s+all intestine. Additionall3, t,ere is a suggestion t,at intestinal b3.ass .ro/ cedures +a3 ,a0e gl3ce+ic e**ects t,at are inde.endent o* t,eir e**ects on 4eig,t, .er,a.s in0ol0ing t,e incretin a2is. T,ere is also e0idence *or diabetes re+ission in subjects 4,o are less obese. One rando+i;ed trial co+.ared adjust/ able gastric banding to =best a0ailable? +edical and li*est3le t,era.3 in subjects 4it, t3.e ( diabetes and B I ( !)8:) 1g@+ 7(!:9. O0erall, F!I o* surgicall3 treated .atients ac,ie0ed =re+ission? o* t,eir di/ abetes co+.ared 4it, %!I o* t,ose trea/ ted +edicall3. T,e latter grou. lost onl3 %.FI o* bod3 4eig,t, suggesting t,at t,eir t,era.3 4as not o.ti+al. O0erall t,e trial ,ad ") subjects, and onl3 %! ( ,ad a B I under !H 1g@+ , +a1ing it di*/ 5cult to generali;e t,ese results 4idel3 to diabetic .atients 4,o are less se0erel3 obese or 4it, longer duration o* diabetes.

In a recent nonrando+i;ed stud3 o* "" ( .eo.le 4it, B I o* !)8!H 1g@+ , EEI o* .artici.ants ,ad re+ission o* t,eir t3.e ( diabetes u. to " 3ears a*ter surger3 7(!H9. Bariatric surger3 is costl3 in t,e s,ort/ ter+ and ,as so+e ris1s. Rates o* +or/ bidit3 and +ortalit3 directl3 related to t,e surger3 ,a0e been reduced considerabl3 in recent 3ears, 4it, !)/da3 +ortalit3 rates no4 ).(EI, si+ilar to t,ose o* la.arosco.ic c,olec3stecto+3 7(!"9. Longer/ter+ concerns include 0ita+in and +ineral de5ciencies, osteo.orosis, and rare but o*ten se0ere ,3.ogl3ce+ia *ro+ insulin ,3.ersecretion. Co,ort studies atte+.ting to +atc, subjects suggest t,at t,e .rocedure +a3 reduce longer/ ter+ +ortalit3 rates 7(!F9. Recent retros.ecti0e anal3ses and +odeling studies suggest t,at t,ese .rocedures +a3 be cost/e**ecti0e, 4,en one considers reduction in subse-uent ,ealt, care costs 7(!E8(:)9. So+e caution about t,e bene5ts o* bariatric surger3 +ig,t co+e *ro+ recent studies. #ro.ensit3 score8adjusted anal/ 3ses o* older se0erel3 obese .atients 4it, ,ig, baseline +ortalit3 in Veterans A*/ *airs edical Centers *ound t,at t,e use o* bariatric surger3 4as not associated 4it, decreased +ortalit3 co+.ared 4it, usual care during a +ean ".F 3ears o* *ollo4/u. 7(:%9. A stud3 t,at *ollo4ed .atients 4,o ,ad undergone la.aro/ sco.ic adjustable gastric banding 7LACB9 *or %( 3ears *ound t,at ")I 4ere satis5ed 4it, t,e .rocedure. $earl3 one out o* t,ree .atients e2.erienced band erosion, and al+ost ,al* re-uired re+o0al o* t,eir bands. T,e aut,ors< con/ clusion 4as t,at =LACB a..ears to result in relati0el3 .oor long/ter+ outco+es? 7(:(9. Studies o* t,e +ec,anis+s o* gl3/ ce+ic i+.ro0e+ent and long/ter+ bene/ 5ts and ris1s o* bariatric surger3 in indi0iduals 4it, t3.e ( diabetes, es.e/ ciall3 t,ose 4,o are not se0erel3 obese, 4ill re-uire 4ell/designed clinical trials, 4it, o.ti+al +edical and li*est3le t,er/ a.3 o* diabetes and cardio0ascular ris1 *actors as t,e co+.arator. . I++uni;ation Reco++endations c Annuall3 .ro0ide an inAuen;a 0accine to all diabetic .atients J" +ont,s o* age. 7C9 c Ad+inister .neu+ococcal .ol3sacc,aride 0accine to all diabetic .atients J( 3ears o* age. A one/ti+e re0accination

is rec/ o++ended *or indi0iduals .": 3ears o*

age .re0iousl3 i++uni;ed 4,en t,e3 4ere ,"H 3ears o* age i* t,e 0accine 4as ad+inistered .H 3ears ago. Ot,er indications *or re.eat 0accination in/ clude ne.,rotic s3ndro+e, c,ronic renal disease, and ot,er i++unoco+/ .ro+ised states, suc, as a*ter trans/ .lantation. 7C9 Ad+inister ,e.atitis B 0accination to un0accinated adults 4it, diabetes 4,o are aged %B t,roug, HB 3ears. 7C9 Consider ad+inistering ,e.atitis B 0ac/ cination to un0accinated adults 4it, diabetes 4,o are aged J") 3ears. 7C9

InAuen;a and .neu+onia are co++on, .re0entable in*ectious diseases associated 4it, ,ig, +ortalit3 and +orbidit3 in t,e elderl3 and in .eo.le 4it, c,ronic dis/ eases. T,oug, t,ere are li+ited studies re.orting t,e +orbidit3 and +ortalit3 o* inAuen;a and .neu+ococcal .neu+onia s.eci5call3 in .eo.le 4it, diabetes, ob/ ser0ational studies o* .atients 4it, a 0a/ riet3 o* c,ronic illnesses, including diabetes, s,o4 t,at t,ese conditions are associated 4it, an increase in ,os.ital/ i;ations *or inAuen;a and its co+.lica/ tions. #eo.le 4it, diabetes +a3 be at increased ris1 o* t,e bactere+ic *or+ o* .neu+ococcal in*ection and ,a0e been re.orted to ,a0e a ,ig, ris1 o* nosoco+ial bactere+ia, 4,ic, ,as a +ortalit3 rate as ,ig, as H)I 7(:!9. Sa*e and e**ecti0e 0accines are a0ail/ able t,at can greatl3 reduce t,e ris1 o* serious co+.lications *ro+ t,ese diseases 7(::,(:H9. In a case/control series, inAu/ en;a 0accine 4as s,o4n to reduce dia/ betes/related ,os.ital ad+ission b3 as +uc, as FBI during Au e.ide+ics 7(::9. T,ere is su*5cient e0idence to su./ .ort t,at .eo.le 4it, diabetes ,a0e a..ro.riate serological and clinical re/ s.onses to t,ese 0accinations. T,e Cen/ ters *or Disease Control and #re0ention 7CDC9 Ad0isor3 Co++ittee on I++uni/ ;ation #ractices reco++ends inAuen;a and .neu+ococcal 0accines *or all indi/ 0iduals 4it, diabetes 7,tt .>@@444.cdc. go0@0 accines@ recs@9. Late in ()%(, t,e Ad0isor3 Co++it/ tee on I++uni;ation #ractices o* t,e CDC reco++ended t,at all .re0iousl3 un0ac/ cinated adults 4it, diabetes aged %B t,roug, HB 3ears be 0accinated against ,e.atitis B 0irus 7DBV9 as soon as .ossible a*ter a diagnosis o* diabetes is +ade and t,at 0accination be considered *or t,ose aged J") 3ears, a*ter assessing ris1 and li1eli,ood o* an ade-uate i++une re/ s.onse 7(:"9. At least (B outbrea1s o*

DBV in long/ter+ care *acilities and ,os/ .itals ,a0e been re.orted to t,e CDC, 4it, t,e +ajorit3 in0ol0ing adults 4it, diabetes recei0ing =assisted blood glucose +onitoring,? in 4,ic, suc, +onitoring is done b3 a ,ealt, care .ro*essional 4it, res.onsibilit3 *or +ore t,an one .atient. DBV is ,ig,l3 trans+issible and stable *or long .eriods o* ti+e on sur*aces suc, as lancing de0ices and blood glucose +eters, e0en 4,en no blood is 0isible. Blood su*/ 5cient to trans+it t,e 0irus ,as also been *ound in t,e reser0oirs o* insulin .ens, resulting in 4arnings against s,aring suc, de0ices bet4een .atients. T,e CDC anal3ses suggest t,at, e2/ cluding .ersons 4it, DBV/related ris1 be,a0iors, acute DBV in*ection is about t4ice as ,ig, a+ong adults 4it, diabetes aged J(! 3ears co+.ared 4it, adults 4it,out diabetes. Sero.re0alence o* anti/ bod3 to DBV core antigen, suggesting .ast or current in*ection, is ")I ,ig,er a+ong adults 4it, diabetes t,an t,ose 4it,out, and t,ere is so+e e0idence t,at diabetes i+.arts a ,ig,er DBV case *atalit3 rate. T,e age di**erentiation in t,e reco++en/ dations ste+s *ro+ CDC econo+ic +od/ els suggesting t,at 0accination o* adults 4it, diabetes 4,o 4ere aged ()8HB 3ears 4ould cost an esti+ated JFH,))) .er -ualit3/adjusted li*e/3ear sa0ed, 4,ile cost .er -ualit3/adjusted li*e/3ear sa0ed increased signi5cantl3 at ,ig,er ages. In addition to co+.eting causes o* +ortalit3 in older adults, t,e i++une res.onse to t,e 0accine declines 4it, age 7(:"9. T,ese ne4 reco++endations regard/ ing DBV 0accinations ser0e as a re+inder to clinicians t,at c,ildren and adults 4it, diabetes need a nu+ber o* 0accinations, bot, t,ose s.eci5call3 indicated because o* diabetes as 4ell as t,ose reco++ended *or t,e general .o.ulation 7,tt.>@@444. cdc.go0@0accines@recs@9. VI. #REVE$TIO$ A$D A$ACE E$T O6 DIABETES CO #LICATIO$S A. CVD CVD is t,e +ajor cause o* +orbidit3 and +ortalit3 *or indi0iduals 4it, diabetes and t,e largest contributor to t,e direct and indirect costs o* diabetes. T,e co++on conditions coe2isting 4it, t3.e ( diabetes 7e.g., ,3.ertension and d3sli.ide+ia9 are clear ris1 *actors *or CVD, and diabetes itsel* con*ers inde.endent ris1. $u+erous studies ,a0e s,o4n t,e e*5cac3 o* con/ trolling indi0idual cardio0ascular ris1 *actors in .re0enting or slo4ing CVD in

.eo.le 4it, diabetes. Large bene5ts are seen 4,en +ulti.le ris1 *actors are ad/ dressed globall3 7(:F,(:E9. T,ere is e0i/ dence t,at +easures o* %)/3ear coronar3 ,eart disease 7CDD9 ris1 a+ong U.S. adults 4it, diabetes ,a0e i+.ro0ed signi*/ icantl3 o0er t,e .ast decade 7(:B9. %. D3.ertension@blood .ressure control Reco++endations Screening and diagnosis c Blood .ressure s,ould be +easured at e0er3 routine 0isit. #atients *ound to ,a0e ele0ated blood .ressure s,ould ,a0e blood .ressure con5r+ed on a se.arate da3. 7B9 Coals c #eo.le 4it, diabetes and ,3.ertension s,ould be treated to a s3stolic blood .ressure goal o* ,%:) ++Dg. 7B9 c Lo4er s3stolic targets, suc, as ,%!) ++Dg, +a3 be a..ro.riate *or certain indi0iduals, suc, as 3ounger .atients, i* it can be ac,ie0ed 4it,out undue treat+ent burden. 7C9 c #atients 4it, diabetes s,ould be treated to a diastolic blood .ressure ,E) ++Dg. 7B9 Treat+ent c #atients 4it, a blood .ressure .%()@ E) ++Dg s,ould be ad0ised on li*e/ st3le c,anges to reduce blood .ressure. 7B9 c #atients 4it, con5r+ed blood .ressure J%:)@E) ++Dg s,ould, in addition to li*est3le t,era.3, ,a0e .ro+.t initia/ tion and ti+el3 subse-uent titration o* .,ar+acological t,era.3 to ac,ie0e blood .ressure goals. 7B9 c Li*est3le t,era.3 *or ele0ated blood .ressure consists o* 4eig,t loss, i* o0er4eig,tO Dietar3 A..roac,es to Sto. D3.ertension 7DASD9/st3le di/ etar3 .attern including reducing so/ diu+ and increasing .otassiu+ inta1eO +oderation o* alco,ol inta1eO and in/ creased .,3sical acti0it3. 7B9 c #,ar+acological t,era.3 *or .atients 4it, diabetes and ,3.ertension s,ould be 4it, a regi+en t,at includes eit,er an ACE in,ibitor or an angiotensin rece.tor bloc1er 7ARB9. I* one class is not tolerated, t,e ot,er s,ould be sub/ stituted. 7C9 c ulti.le/drug t,era.3 7t4o or +ore agents at +a2i+al doses9 is generall3

re-uired to ac,ie0e blood .ressure targets. 7B9 c Ad+inister one or +ore anti,3.erten/ si0e +edications at bedti+e. 7A9

I* ACE in,ibitors, ARBs, or diuretics are used, seru+ creatinine@esti+ated glo/ +erular 5ltration rate 7eC6R9 and seru+ .otassiu+ le0els s,ould be +onitored. 7E9 In .regnant .atients 4it, diabetes and c,ronic ,3.ertension, blood .ressure target goals o* %%)8%(B@"H8FB ++Dg are suggested in t,e interest o* long/ ter+ +aternal ,ealt, and +ini+i;ing i+.aired *etal gro4t,. ACE in,ibitors and ARBs are contraindicated during .regnanc3. 7E9

D3.ertension is a co++on co+or/ bidit3 o* diabetes, a**ecting t,e +ajorit3 o* .atients, 4it, .re0alence de.ending on t3.e o* diabetes, age, obesit3, and et,nic/ it3. D3.ertension is a +ajor ris1 *actor *or bot, CVD and +icro0ascular co+.lica/ tions. In t3.e % diabetes, ,3.ertension is o*ten t,e result o* underl3ing ne.,ro.a/ t,3, 4,ile in t3.e ( diabetes it usuall3 coe2ists 4it, ot,er cardio+etabolic ris1 *actors. Screening and diagnosis easure+ent o* blood .ressure in t,e o*5ce s,ould be done b3 a trained in/ di0idual and *ollo4 t,e guidelines es/ tablis,ed *or nondiabetic indi0iduals> +easure+ent in t,e seated .osition, 4it, *eet on t,e Aoor and ar+ su..orted at ,eart le0el, a*ter H +in o* rest. Cu** si;e s,ould be a..ro.riate *or t,e u..er ar+ circu+*erence. Ele0ated 0alues s,ould be con5r+ed on a se.arate da3. Do+e blood .ressure sel*/+onitoring and (:/, a+bulator3 blood .ressure +onitoring +a3 .ro0ide additional e0i/ dence o* =4,ite coat? and +as1ed ,3.er/ tension and ot,er discre.ancies bet4een o*5ce and =true? blood .ressure. Studies in nondiabetic .o.ulations *ound t,at ,o+e +easure+ents +a3 better correlate 4it, CVD ris1 t,an o*5ce +easure+ents 7(H),(H%9. Do4e0er, t,e .re.onderance o* t,e e0idence o* bene5ts o* treat+ent o* ,3.ertension in .eo.le 4it, diabetes is based on o*5ce +easure+ents. Treat+ent goals E.ide+iological anal3ses s,o4 t,at blood .ressure .%%H@FH ++Dg is associated 4it, increased cardio0ascular e0ent rates and +ortalit3 in indi0iduals 4it, diabetes 7(H(8(H:9 and t,at s3stolic blood .res/ sure abo0e %() ++Dg .redicts long/ter+ end/stage renal disease 7ESRD9. Rando+/ i;ed clinical trials ,a0e de+onstrated t,e bene5t 7reduction o* CDD e0ents, stro1e, and ne.,ro.at,39 o* lo4ering blood

.ressure to ,%:) ++Dg s3stolic and ,E) ++Dg diastolic in indi0iduals 4it, diabetes 7(H(,(HH8(HF9. T,e e0idence *or bene5ts *ro+ lo4er s3stolic blood .res/ sure targets is, ,o4e0er, li+ited. T,e ACCORD trial e2a+ined 4,et,er blood .ressure lo4ering to s3s/ tolic blood .ressure ,%() ++Dg .ro/ 0ides greater cardio0ascular .rotection t,an a s3stolic blood .ressure le0el o* %!)8%:) ++Dg in .atients 4it, t3.e ( diabetes at ,ig, ris1 *or CVD 7(HE9. T,e blood .ressure ac,ie0ed in t,e intensi0e grou. 4as %%B@": ++Dg and in t,e stan/ dard grou. %!!@F) ++DgO t,e goals 4ere attained 4it, an a0erage o* !.: +edica/ tions .er .artici.ant in t,e intensi0e grou. and (.% in t,e standard t,era.3 grou.. T,e ,a;ard ratio *or t,e .ri+ar3 end .oint 7non*atal I, non*atal stro1e, and CVD deat,9 in t,e intensi0e grou. 4as ).EE 7BHI CI ).F!8%.)", # H ).()9. O* t,e .res.eci5ed secondar3 end .oints, onl3 stro1e and non*atal stro1e 4ere sta/ tisticall3 signi5cantl3 reduced b3 inten/ si0e blood .ressure treat+ent, 4it, a ,a;ard ratio o* ).HB 7BHI CI ).!B8).EB, # H ).)%9 and )."! 7BHI CI ).:%8).B", # H ).)!9, res.ecti0el3. Absolute stro1e e0ent rates 4ere lo4O t,e nu+ber needed to treat to .re0ent one stro1e o0er t,e course o* H 3ears 4it, intensi0e blood .ressure +anage+ent is EB. Serious ad/ 0erse e0ent rates 7including s3nco.e and ,3.er1ale+ia9 4ere ,ig,er 4it, intensi0e targets 7!.!I 0s. %.!I, # H ).))%9. Rates o* albu+inuria 4ere reduced 4it, +ore intensi0e blood .ressure goals, but t,ere 4ere no di**erences in renal *unction in t,is H/3ear trial 7and in *act +ore ad0erse e0ents related to reduced eC6R 4it, +ore intensi0e goals9 nor in ot,er +icro0ascu/ lar co+.lications. Ot,er recent rando+i;ed trial data include t,ose o* t,e ADVA$CE trial in 4,ic, treat+ent 4it, an ACE in,ibitor and a t,ia;ide/t3.e diuretic reduced t,e rate o* deat, but not t,e co+.osite +acro0ascular outco+e. Do4e0er, t,e ADVA$CE trial ,ad no s.eci5ed targets *or t,e rando+i;ed co+.arison, and t,e +ean s3stolic blood .ressure in t,e in/ tensi0e grou. 7%!H ++Dg9 4as not as lo4 as t,e +ean s3stolic blood .ressure e0en in t,e ACCORD standard/t,era.3 grou. 7(HB9. #ost ,oc anal3sis o* ac,ie0ed blood .ressure in se0eral ,3.ertension treat/ +ent trials ,as suggested no bene5t o* lo4er ac,ie0ed s3stolic blood .ressure.

As an e2a+.le, a+ong ",:)) .atients 4it, diabetes and CAD enrolled in one trial, =tig,t control? 7ac,ie0ed s3stolic

blood .ressure ,%!) ++Dg9 4as not as/ sociated 4it, i+.ro0ed cardio0ascular outco+es co+.ared 4it, =usual care? 7ac,ie0ed s3stolic blood .ressure %!)8 %:) ++Dg9 7(")9. Si+ilar 5nding e+erged *ro+ an anal3sis o* anot,er trial, but additionall3 t,ose 4it, ac,ie0ed s3s/ tolic blood .ressure 7,%%H ++Dg9 ,ad increased rates o* CVD e0ents 7t,oug, lo4er rates o* stro1e9 7("%9. Obser0ational data, including t,ose deri0ed *ro+ clinical trials, +a3 be in/ a..ro.riate to use *or de5ning blood .ressure targets since sic1er .atients +a3 ,a0e lo4 blood .ressure or, con/ 0ersel3, ,ealt,ier or +ore ad,erent .a/ tients +a3 ac,ie0e goals +ore readil3. A recent +eta/anal3sis o* rando+i;ed trials o* adults 4it, t3.e ( diabetes co+.aring .res.eci5ed blood .ressure targets *ound no signi5cant reduction in +ortalit3 or non*atal I. T,ere 4as a statisticall3 signi5cant !HI relati0e reduction in stro1e, but t,e absolute ris1 reduction 4as onl3 %I 7("(9. Ot,er outco+es, suc, as indicators o* +icro0ascular co+.lica/ tions, 4ere not e2a+ined. Anot,er +eta/anal3sis t,at included bot, trials co+.aring blood .ressure goals and trials co+.aring treat+ent strategies con/ cluded t,at a s3stolic treat+ent goal o* %!)8%!H ++Dg 4as acce.table. Kit, goals ,%!) ++Dg, t,ere 4ere greater re/ ductions in stro1e, a %)I reduction in +ortalit3, but no reduction o* ot,er CVD e0ents and increased rates o* serious ad0erse e0ents. S3stolic blood .ressure ,%!) ++Dg 4as associated 4it, re/ duced onset and .rogression o* albu+in/ uria. Do4e0er, t,ere 4as ,eterogeneit3 in t,e +easure, rates o* +ore ad0anced renal disease outco+es 4ere not a**ected, and t,ere 4ere no signi5cant c,anges in reti/ no.at,3 or neuro.at,3 7("!9. T,is c,ange in t,e =de*ault? s3stolic blood .ressure target is not +eant to do4n.la3 t,e i+.ortance o* treating ,3/ .ertension in .atients 4it, diabetes or to i+.l3 t,at lo4er targets t,an ,%:) ++Dg are generall3 ina..ro.riate. T,e clear bod3 o* e0idence t,at s3stolic blood .ressure o0er %:) ++Dg is ,ar+*ul sug/ gests t,at clinicians s,ould .ro+.tl3 ini/ tiate and titrate t,era.3 in an ongoing *as,ion to ac,ie0e and +aintain s3stolic blood .ressure belo4 %:) ++Dg in 0ir/ tuall3 all .atients.
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Additionall3, .atients 4it, long li*e e2.ectanc3 7in 4,o+ t,ere +a3 be renal bene5ts *ro+ long/ter+ stricter blood .ressure control9 or t,ose in 4,o+ stro1e ris1 is a concern +ig,t, as .art o* s,ared decision +a1ing,

a..ro.riatel3 ,a0e lo4er s3stolic targets suc, as ,%!) ++Dg. T,is 4ould es.e/ ciall3 be t,e case i* t,is can be ac,ie0ed 4it, *e4 drugs and 4it,out side e**ects o* t,era.3. Treat+ent strategies Alt,oug, t,ere are no 4ell/controlled studies o* diet and e2ercise in t,e treat/ +ent o* ele0ated blood .ressure or ,3/ .ertension in indi0iduals 4it, diabetes, t,e DASD stud3 in nondiabetic indi0idu/ als ,as s,o4n anti,3.ertensi0e e**ects si+ilar to .,ar+acological +onot,era.3. Li*est3le t,era.3 consists o* reducing sodiu+ inta1e 7to belo4 %,H)) +g@da39 and e2cess bod3 4eig,tO increasing con/ su+.tion o* *ruits, 0egetables 7E8%) ser0/ ings .er da39, and lo4/*at dair3 .roducts 7(8! ser0ings .er da39O a0oiding e2cessi0e alco,ol consu+.tion 7no +ore t,an t4o ser0ings .er da3 *or +en and no +ore t,an one ser0ing .er da3 *or 4o+en9 7(":9O and increasing acti0it3 le0els 7(H(9. T,ese non.,ar+acological strate/ gies +a3 also .ositi0el3 a**ect gl3ce+ia and li.id control and as a result s,ould be encouraged in t,ose 4it, e0en +ildl3 ele0ated blood .ressure. T,eir e**ects on cardio0ascular e0ents ,a0e not been es/ tablis,ed. $on.,ar+acological t,era.3 is reasonable in diabetic indi0iduals 4it, +ildl3 ele0ated blood .ressure 7s3stolic blood .ressure .%() ++Dg or diastolic blood .ressure .E) ++Dg9. I* t,e blood .ressure is con5r+ed to be J%:) ++Dg s3stolic and@or JE) ++Dg diastolic, .,ar+acological t,era.3 s,ould be initi/ ated along 4it, non.,ar+acological t,era.3 7(H(9. Lo4ering o* blood .ressure 4it, regi/ +ens based on a 0ariet3 o* anti,3.ertensi0e drugs, including ACE in,ibitors, ARBs, b/bloc1ers, diuretics, and calciu+ c,annel bloc1ers, ,as been s,o4n to be e**ecti0e in reducing cardio0ascular e0ents. Se0eral studies suggested t,at ACE in,ibitors +a3 be su.erior to di,3dro.3ridine calciu+ c,annel bloc1ers in reducing cardio0ascu/ lar e0ents 7("H8("F9. Do4e0er, a 0ariet3 o* ot,er studies ,a0e s,o4n no s.eci5c ad/ 0antage to ACE in,ibitors as initial treat/ +ent o* ,3.ertension in t,e general ,3.ertensi0e .o.ulation, but rat,er an ad/ 0antage on cardio0ascular outco+es o* ini/ tial t,era.3 4it, lo4/dose t,ia;ide diuretics 7(H(,("E,("B9. In .eo.le 4it, diabetes, in,ibitors o* t,e renin/angiotensin s3ste+ 7RAS9 +a3 ,a0e uni-ue ad0antages *or initial or earl3 t,era.3 o* ,3.ertension. In a non,3.er/ tension trial o* ,ig,/ris1 indi0iduals,
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including a large subset 4it, diabetes, an ACE in,ibitor reduced CVD outco+es 7(F)9. In .atients 4it, congesti0e ,eart *ailure 7CD69, including diabetic sub/ grou.s, ARBs ,a0e been s,o4n to reduce +ajor CVD outco+es 7(F%8(F:9, and in t3.e ( diabetic .atients 4it, signi5cant ne.,ro.at,3, ARBs 4ere su.erior to cal/ ciu+ c,annel bloc1ers *or reducing ,eart *ailure 7(FH9. T,oug, e0idence *or dis/ tinct ad0antages o* RAS in,ibitors on CVD outco+es in diabetes re+ains con/ Aicting 7(HH,("B9, t,e ,ig, CVD ris1s as/ sociated 4it, diabetes, and t,e ,ig, .re0alence o* undiagnosed CVD, +a3 still *a0or reco++endations *or t,eir use as 5rst/line ,3.ertension t,era.3 in .eo.le 4it, diabetes 7(H(9. Recentl3, t,e blood .ressure ar+ o* t,e ADVA$CE trial de+onstrated t,at routine ad+inistration o* a 52ed co+bi/ nation o* t,e ACE in,ibitor .erindo.ril and t,e diuretic inda.a+ide signi5cantl3 reduced co+bined +icro0ascular and +acro0ascular outco+es, as 4ell as CVD and total +ortalit3. T,e i+.ro0ed out/ co+es could also ,a0e been due to lo4er ac,ie0ed blood .ressure in t,e .erindo.ril/inda.a+ide ar+ 7(HB9. An/ ot,er trial s,o4ed a decrease in +orbidit3 and +ortalit3 in t,ose recei0ing bena;e/ .ril and a+lodi.ine co+.ared 4it, bena/ ;e.ril and ,3droc,lorot,ia;ide 7DCTV9. T,e co+.elling bene5ts o* RAS in,ibitors in diabetic .atients 4it, albu+inuria or renal insu*5cienc3 .ro0ide additional ra/ tionale *or use o* t,ese agents 7see Section VI.B9. I* needed to ac,ie0e blood .ressure targets, a+lodi.ine, DCTV, or c,lort,ali/ done can be added. I* eC6R is ,!) +L@ ( +in@+ , a loo. diuretic rat,er t,an DCTV or c,lort,alidone s,ould be .rescribed. Titration o* and@or addition o* *urt,er blood .ressure +edications s,ould be +ade in ti+el3 *as,ion to o0erco+e clin/ ical inertia in ac,ie0ing blood .ressure targets. E0idence is e+erging t,at ,ealt, in/ *or+ation tec,nolog3 can be used sa*el3 and e**ecti0el3 as a tool to enable attain/ +ent o* blood .ressure goals. Using a tele+onitoring inter0ention to direct titrations o* anti,3.ertensi0e +edications bet4een +edical o*5ce 0isits ,as been de+onstrated to ,a0e a .ro*ound i+.act on s3stolic blood .ressure control 7(F"9. An i+.ortant ca0eat is t,at +ost .atients 4it, ,3.ertension re-uire +ulti.le/drug t,era.3 to reac, treat+ent goals 7(H(9. Identi*3ing and addressing barriers to +edication ad,erence 7suc, as cost and side e**ects9 s,ould routinel3
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%, &A$UAR' ()%!

S! %!%

be done. I* blood .ressure is re*ractor3 des.ite con5r+ed ad,erence to o.ti+al doses o* at least t,ree anti,3.ertensi0e agents o* di**erent classi5cations, one o* 4,ic, s,ould be a diuretic, clinicians s,ould consider an e0aluation *or sec/ ondar3 *or+s o* ,3.ertension. Cro4ing e0idence suggests t,at t,ere is an associ/ ation bet4een increase in slee./ti+e blood .ressure and incidence o* CVD e0ents. A recent RCT o* ::E .artici.ants 4it, t3.e ( diabetes and ,3.ertension de+onstrated reduced cardio0ascular e0ents an d + ortalit3 4it, +edian *ollo4/u. o* H.: 3ears i* at least one an/ ti,3.ertensi0e +edication 4as gi0en at bedti+e 7(FF9. During .regnanc3 in diabetic 4o+en 4it, c,ronic ,3.ertension, target blood .ressure goals o* s3stolic blood .ressure %%)8%(B ++Dg and diastolic blood .res/ sure "H8FB ++Dg are reasonable, as t,e3 contribute to long/ter+ +aternal ,ealt,. Lo4er blood .ressure le0els +a3 be asso/ ciated 4it, i+.aired *etal gro4t,. During .regnanc3, treat+ent 4it, ACE in,ibi/ tors and ARBs is contraindicated because t,e3 can cause *etal da+age. Anti,3.er/ tensi0e drugs 1no4n to be e**ecti0e and sa*e in .regnanc3 include +et,3ldo.a, labetalol, diltia;e+, clonidine, and .ra/ ;osin. C,ronic diuretic use during .reg/ nanc3 ,as been associated 4it, restricted +aternal .las+a 0olu+e, 4,ic, +ig,t reduce utero.lacental .er*usion 7(FE9. (. D3sli.ide+ia@li.id +anage+ent Reco++endations Screening c In +ost adult .atients 4it, diabetes, +easure *asting li.id .ro5le at least annuall3. 7B9 c In adults 4it, lo4/ris1 li.id 0alues 7LDL c,olesterol ,%)) +g@dL, DDL c,olesterol .H) +g@dL, and trigl3/ cerides ,%H) +g@dL9, li.id assess+ents +a3 be re.eated e0er3 ( 3ears. 7E9 Treat+ent reco++endations and goals c Li*est3le +odi5cation *ocusing on t,e reduction o* saturated *at, trans *at, and c,olesterol inta1eO increase o* n/! *att3 acids, 0iscous 5ber, and .lant stanols@ sterolsO 4eig,t loss 7i* indicated9O and increased .,3sical acti0it3 s,ould be reco++ended to i+.ro0e t,e li.id .ro5le in .atients 4it, diabetes. 7A9

Statin t,era.3 s,ould be added to li*e/ st3le t,era.3, regardless o* baseline li.id le0els, *or diabetic .atients> c 4it, o0ert CVD 7A9 c 4it,out CVD 4,o are o0er t,e age o* :) 3ears and ,a0e one or +ore ot,er

CVD ris1 *actors 7*a+il3 ,istor3 o* CVD, ,3.ertension, s+o1ing, d3sli/ .ide+ia, or albu+inuria9 7A9 6or lo4er/ris1 .atients t,an t,e abo0e 7e.g., 4it,out o0ert CVD and under t,e age o* :) 3ears9, statin t,era.3 s,ould be considered in addition to li*est3le t,era.3 i* LDL c,olesterol re+ains abo0e %)) +g@dL or in t,ose 4it, +ulti.le CVD ris1 *actors. 7C9 In indi0iduals 4it,out o0ert CVD, t,e goal is LDL c,olesterol ,%)) +g@dL 7(." ++ol@L9. 7B9 In indi0iduals 4it, o0ert CVD, a lo4er LDL c,olesterol goal o* ,F) +g@dL 7%.E ++ol@L9, using a ,ig, dose o* a statin, is an o.tion. 7B9 I* drug/treated .atients do not reac, t,e abo0e targets on +a2i+al tolerated statin t,era.3, a reduction in LDL c,olesterol o* O!)8:)I *ro+ baseline is an alternati0e t,era.eutic goal. 7B9 Trigl3cerides le0els ,%H) +g@dL 7%.F ++ol@L9 and DDL c,olesterol .:) +g@dL 7%.) ++ol@L9 in +en and .H) +g@dL 7%.! ++ol@L9 in 4o+en are desirable 7C9. Do4e0er, LDL c,olesterol8 targeted statin t,era.3 re+ains t,e .re*erred strateg3. 7A9 Co+bination t,era.3 ,as been s,o4n not to .ro0ide additional cardio0ascu/ lar bene5t abo0e statin t,era.3 alone and is not generall3 reco++ended. 7A9 Statin t,era.3 is contraindicated in .regnanc3. 7B9

E0idence *or bene5ts o* li.id/lo4ering t,era.3 #atients 4it, t3.e ( diabetes ,a0e an increased .re0alence o* li.id abnor+ali/ ties, contributing to t,eir ,ig, ris1 o* CVD. ulti.le clinical trials de+on/ strated signi5cant e**ects o* .,ar+acolog/ ical 7.ri+aril3 statin9 t,era.3 on CVD outco+es in subjects 4it, CDD and *or .ri+ar3 CVD .re0ention 7(FB,(E)9. Sub/ anal3ses o* diabetic subgrou.s o* larger trials 7(E%8(EH9 and trials s.eci5call3 in subjects 4it, diabetes 7(E",(EF9 s,o4ed signi5cant .ri+ar3 and secondar3 .re/ 0ention o* CVD e0ents %@( CDD deat,s in diabetic .o.ulations. eta/anal3ses in/ cluding data *ro+ o0er %E,))) .atients 4it, diabetes *ro+ %: rando+i;ed trials o* statin t,era.3, *ollo4ed *or a +ean o* :.! 3ears, de+onstrate a BI .ro.ortional reduction in all/cause +ortalit3 and %!I reduction in 0ascular +ortalit3, *or eac, ++ol@L reduction in LDL c,olesterol 7(EE9. As is t,e case in nondiabetic indi/ 0iduals, absolute reductions in =,ard? CVD outco+es 7CDD deat, and non*atal

I9 are greatest in .eo.le 4it, ,ig, base/ line CVD ris1 71no4n CVD and@or 0er3 ,ig, LDL c,olesterol le0els9, but o0erall t,e bene5ts o* statin t,era.3 in .eo.le 4it, diabetes at +oderate or ,ig, ris1 *or CVD are con0incing. T,ere is an increased ris1 o* incident diabetes 4it, statin use 7(EB,(B)9, 4,ic, +a3 be li+ited to t,ose 4it, ris1 *actors *or diabetes. T,ese .atients +a3 bene5t additionall3 *ro+ diabetes screening 4,en on statin t,era.3. In an anal3sis o* one o* t,e initial studies suggesting t,at statins are lin1ed to ris1 o* diabetes, t,e cardio0ascular e0ent rate reduction 4it, statins out4eig,ed t,e ris1 o* incident di/ abetes e0en *or .atients at ,ig,est ris1 *or diabetes. T,e absolute ris1 increase 4as s+all 7o0er H 3ears o* *ollo4/u., %.(I o* .artici.ants on .lacebo de0elo.ed diabe/ tes and %.HI on rosu0astatin9 7(B%9. T,e relati0e ris1/bene5t ratio *a0oring statins is *urt,er su..orted b3 +eta/anal3sis o* indi0idual data o* o0er %F),))) .ersons *ro+ (F rando+i;ed trials. T,is de+on/ strated t,at indi0iduals at lo4 ris1 o* 0as/ cular disease, including t,ose undergoing .ri+ar3 .re0ention, recei0ed bene5ts *ro+ statins t,at included reductions in +ajor 0ascular e0ents and 0ascular deat, 4it,out increase in incidence o* cancer or deat,s *ro+ ot,er causes 7(E)9. Lo4 le0els o* DDL c,olesterol, o*ten associated 4it, ele0ated trigl3ceride le0/ els, are t,e +ost .re0alent .attern o* d3sli.ide+ia in .ersons 4it, t3.e ( di/ abetes. Do4e0er, t,e e0idence base *or drugs t,at target t,ese li.id *ractions is signi5cantl3 less robust t,an t,at *or statin t,era.3 7(B(9. $icotinic acid ,as been s,o4n to reduce CVD outco+es 7(B!9, alt,oug, t,e stud3 4as done in a nondiabetic co,ort. Ce+5bro;il ,as been s,o4n to decrease rates o* CVD e0ents in subjects 4it,out diabetes 7(B:,(BH9 and in t,e diabetic subgrou. o* one o* t,e larger trials 7(B:9. Do4e0er, in a large trial s.eci5c to diabetic .atients, *eno5brate *ailed to reduce o0erall cardio0ascular outco+es 7(B"9. Co+bination t,era.3, 4it, a statin and a 5brate or statin and niacin, +a3 be e*5cacious *or treat+ent *or all t,ree li.id *ractions, but t,is co+bination is associ/ ated 4it, an increased ris1 *or abnor+al transa+inase le0els, +3ositis, or r,abdo/ +3ol3sis. T,e ris1 o* r,abdo+3ol3sis is ,ig,er 4it, ,ig,er doses o* statins and 4it, renal insu*5cienc3 and see+s to be lo4er 4,en statins are co+bined 4it, *eno5brate t,an ge+5bro;il 7(BF9. In t,e ACCORD stud3, t,e co+bination o*

*eno5brate and si+0astatin did not re/ duce t,e rate o* *atal cardio0ascular e0ents, non*atal I, or non*atal stro1e, as co+.ared 4it, si+0astatin alone, in .atients 4it, t3.e ( diabetes 4,o 4ere at ,ig, ris1 *or CVD. #res.eci5ed sub/ grou. anal3ses suggested ,eterogeneit3 in treat+ent e**ects according to se2, 4it, a bene5t o* co+bination t,era.3 *or +en and .ossible ,ar+ *or 4o+en, and a .ossible bene5t *or .atients 4it, bot, trigl3ceride le0el J(): +g@dL and DDL c,olesterol le0el S!: +g@dL 7(BE9. T,e AI /DICD trial rando+i;ed o0er !,))) .atients 7about one/t,ird 4it, di/ abetes9 4it, establis,ed CVD, lo4 le0els o* DDL c,olesterol, and trigl3ceride le0els o* %H)8:)) +g@dL to statin t,era.3 .lus e2tended release niacin or +atc,ing .la/ cebo. T,e trial 4as ,alted earl3 due to lac1 o* e*5cac3 on t,e .ri+ar3 CVD outco+e and a .ossible increase in isc,e+ic stro1e in t,ose on co+bination t,era.3 7(BB9. Dence, co+bination li.id/lo4ering t,er/ a.3 cannot be broadl3 reco++ended. D3sli.ide+ia treat+ent and target li.id le0els 6or +ost .atients 4it, diabetes, t,e 5rst .riorit3 o* d3sli.ide+ia t,era.3 7unless se0ere ,3.ertrigl3ceride+ia 4it, ris1 o* .ancreatitis is t,e i++ediate issue9 is to lo4er LDL c,olesterol to a target goal o* ,%)) +g@dL 7(.") ++ol@L9 7!))9. Li*e/ st3le inter0ention, including $T, in/ creased .,3sical acti0it3, 4eig,t loss, and s+o1ing cessation, +a3 allo4 so+e .atients to reac, li.id goals. $utrition in/ ter0ention s,ould be tailored according to eac, .atient<s age, t3.e o* diabetes, .,ar/ +acological treat+ent, li.id le0els, and ot,er +edical conditions and s,ould *o/ cus on t,e reduction o* saturated *at, c,o/ lesterol, and trans unsaturated *at inta1e and increases in n/! *att3 acids, 0iscous 5ber 7suc, as in oats, legu+es, citrus9, and .lant stanols@sterols. Cl3ce+ic con/ trol can also bene5ciall3 +odi*3 .las+a li.id le0els, .articularl3 in .atients 4it, 0er3 ,ig, trigl3cerides and .oor gl3ce+ic control. In t,ose 4it, clinical CVD or o0er age :) 3ears 4it, ot,er CVD ris1 *actors, .,ar+acological treat+ent s,ould be added to li*est3le t,era.3 regardless o* baseline li.id le0els. Statins are t,e drugs o* c,oice *or LDL c,olesterol lo4ering

and cardio.rotection. In .atients ot,er t,an t,ose described abo0e, statin treat/ +ent s,ould be considered i* t,ere is an inade-uate LDL c,olesterol res.onse to li*est3le +odi5cations and i+.ro0ed

glucose control, or i* t,e .atient ,as increased cardio0ascular ris1 7e.g., +ulti/ .le cardio0ascular ris1 *actors or long duration o* diabetes9. Ver3 little clinical trial e0idence e2ists *or t3.e ( diabetic .atients under t,e age :) 3ears, or *or t3.e % diabetic .atients o* an3 age. In t,e Deart #rotection Stud3 7lo4er age li+it :) 3ears9, t,e subgrou. o* O")) .atients 4it, t3.e % diabetes ,ad a reduction in ris1 .ro.ortionatel3 si+ilar to t,at o* .a/ tients 4it, t3.e ( diabetes, alt,oug, not statisticall3 signi5cant 7(E(9. Alt,oug, t,e data are not de5niti0e, consideration s,ould be gi0en to si+ilar li.id/lo4ering goals in t3.e % diabetic .atients as in t3.e ( diabetic .atients, .articularl3 i* t,e3 ,a0e ot,er cardio0ascular ris1 *actors. Alternati0e li.o.rotein goals Virtuall3 all trials o* statins and CVD outco+e tested s.eci5c doses o* statins against .lacebo, ot,er doses o* statin, or ot,er statins, rat,er t,an ai+ing *or s.e/ ci5c LDL c,olesterol goals 7!)%9. #lacebo/ controlled trials generall3 ac,ie0ed LDL c,olesterol reductions o* !)8:)I *ro+ baseline. Dence, LDL c,olesterol lo4er/ ing o* t,is +agnitude is an acce.table out/ co+e *or .atients 4,o cannot reac, LDL c,olesterol goals due to se0ere baseline ele0ations in LDL c,olesterol and@or in/ tolerance o* +a2i+al, or an3, statin doses. Additionall3 *or t,ose 4it, baseline LDL c,olesterol +ini+all3 abo0e %)) +g@dL, .rescribing statin t,era.3 to lo4er LDL c,olesterol about !)8:)I *ro+ baseline is .robabl3 +ore e**ecti0e t,an .rescrib/ ing just enoug, to get LDL c,olesterol slig,tl3 belo4 %)) +g@dL. Clinical trials in ,ig,/ris1 .atients, suc, as t,ose 4it, acute coronar3 s3n/ dro+es or .re0ious cardio0ascular e0ents 7!)(8!):9, ,a0e de+onstrated t,at +ore aggressi0e t,era.3 4it, ,ig, doses o* sta/ tins to ac,ie0e an LDL c,olesterol o* ,F) +g@dL led to a signi5cant reduction in *urt,er e0ents. T,ere*ore, a reduction in LDL c,olesterol to a goal o* ,F) +g@dL is an o.tion in 0er3 ,ig,/ris1 diabetic .a/ tients 4it, o0ert CVD 7!)H9. So+e e2/ .erts reco++end a greater *ocus on non8DDL c,olesterol, a.oli.o.rotein B 7a.oB9, or li.o.rotein .article +easure/ +ents to assess residual CVD ris1 in statin/treated .atients 4,o are li1el3 to ,a0e s+all LDL .articles, suc, as .eo.le 4it, diabetes 7!)"9, but it is unclear 4,et,er clinical +anage+ent 4ould c,ange 4it, t,ese +easure+ents. In indi0idual .atients, LDL c,oles/ terol lo4ering 4it, statins is ,ig,l3

0ariable, and t,is 0ariable res.onse is .oorl3 understood 7!)F9. Reduction o* CVD e0ents 4it, statins correlates 0er3 closel3 4it, LDL c,olesterol lo4ering 7(FB9. I* initial atte+.ts to .rescribe a statin leads to side e**ects, clinicians s,ould atte+.t to 5nd a dose or alterna/ ti0e statin t,at t,e .atient can tolerate. T,ere is e0idence *or signi5cant LDL c,olesterol lo4ering *ro+ e0en e2/ tre+el3 lo4, less t,an dail3, statin doses 7!)E9. K,en +a2i+all3 tolerated doses o* statins *ail to signi5cantl3 lo4er LDL c,olesterol 7,!)I reduction *ro+ t,e .atient<s baseline9, t,ere is no strong e0/ idence t,at co+bination t,era.3 s,ould be used to ac,ie0e additional LDL c,o/ lesterol lo4ering. $iacin, *eno5brate, e;eti+ibe, and bile acid se-uestrants all o**er additional LDL c,olesterol lo4ering to statins alone, but 4it,out e0idence t,at suc, co+bination t,era.3 *or LDL c,olesterol lo4ering .ro0ides a signi5/ cant incre+ent in CVD ris1 reduction o0er statin t,era.3 alone. Treat+ent o* ot,er li.o.rotein *rac/ tions or targets D3.ertrigl3ceride+ia s,ould be ad/ dressed 4it, dietar3 and li*est3le c,anges. Se0ere ,3.ertrigl3ceride+ia 7.%,))) +g@dL9 +a3 4arrant i++ediate .,ar+a/ cological t,era.3 75bric acid deri0ati0e, niacin, or 5s, oil9 to reduce t,e ris1 o* acute .ancreatitis. In t,e absence o* se/ 0ere ,3.ertrigl3ceride+ia, t,era.3 target/ ing DDL c,olesterol or trigl3cerides lac1s t,e strong e0idence base o* statin t,era.3. I* t,e DDL c,olesterol is ,:) +g@dL and t,e LDL c,olesterol is bet4een %)) and %(B +g@dL, a 5brate or niacin +ig,t be used, es.eciall3 i* a .atient is intolerant to statins. $iacin is t,e +ost e**ecti0e drug *or raising DDL c,olesterol. It can signi*/ icantl3 increase blood glucose at ,ig, doses, but at +odest doses 7FH)8(,))) +g@da39 signi5cant i+.ro0e+ents in LDL c,oles/ terol, DDL c,olesterol, and trigl3ceride le0els are acco+.anied b3 onl3 +odest c,anges in glucose t,at are generall3 a+e/ nable to adjust+ent o* diabetes t,era.3 7(BB,!)B,!%)9. Table %) su++ari;es co++on treat/ +ent goals *or A%C, blood .ressure, and LDL c,olesterol. !. Anti.latelet agents Reco++endations c Consider as.irin t,era.3 7FH8%"(

+g@da39 as a .ri+ar3 .re0ention strateg3 in t,ose 4it, t3.e % or t3.e ( diabetes

T,e Antit,ro+botic Trialists< 7ATT9 collaborators recentl3 .ublis,ed an indi/ 0idual .atient/le0el +eta/anal3sis o* t,e si2 large trials o* as.irin *or .ri+ar3 .re/ 0ention in t,e general .o.ulation. T,ese trials collecti0el3 enrolled o0er BH,))) .artici.ants, including al+ost c :,))) 4it, diabetes. O0erall, t,e3 *ound t,at as/ .irin reduced t,e ris1 o* 0ascular e0ents b3 %(I 7RR ).EE, BHI CI ).E(8).B:9. T,e largest reduction 4as *or non*atal I 4it, little e**ect on CDD deat, 7RR ).BH, BHI CI ).FE8%.%H9 or total stro1e. T,ere 4as so+e e0idence o* a di**erence in as.irin e**ect b3 se2. As.irin signi5/ cantl3 reduced CDD e0ents in +en but not in 4o+en. Con0ersel3, as.irin ,ad c no e**ect on stro1e in +en but signi5/ cantl3 reduced stro1e in 4o+en. $otabl3, se2 di**erences in as.irin<s e**ects ,a0e not been obser0ed in c studies o* secondar3 .re0ention 7!%%9. In t,e si2 trials e2a+/ ined b3 t,e ATT collaborators, t,e e**ects o* as.irin on +ajor 0ascular e0ents 4ere c si+ilar *or .atients 4it, or 4it,out diabe/ tes> RR ).EE 7BHI CI )."F8%.%H9 and c ).EF 7BHI CI ).FB8).B"9, res.ecti0el3. T,e con5dence inter0al 4as 4ider *or t,ose 4it, diabetes because o* t,eir s+aller As.irin ,as been s,o4n to be nu+ber. Based on t,e currentl3 a0ailable e0i/ e**ecti0e in reducing cardio0ascular +orbidit3 and +ortalit3 in ,ig,/ris1 dence, as.irin a..ears to ,a0e a +odest .atients 4it, .re/ 0ious I or stro1e e**ect on isc,e+ic 0ascular e0ents 4it, 7secondar3 .re0ention9. Its net bene5t in t,e absolute decrease in e0ents de.end/ .ri+ar3 .re0ention a+ong .atients 4it, ing on t,e underl3ing CVD ris1. T,e no .re0ious cardio/ 0ascular e0ents is +ain ad0erse e**ects a..ear to be an +ore contro0ersial, bot, *or .atients 4it, increased ris1 o* gastrointestinal bleed/ and 4it,out a ,istor3 o* diabetes 7!%%9. ing. T,e e2cess ris1 +a3 be as ,ig, as %8 T4o recent RCTs o* as.irin s.eci5call3 in H .atients 4it, diabetes *ailed to s,o4 a .er %,))) .er 3ear in real/4orld settings. signi5cant reduction in CVD end .oints, In adults 4it, CVD ris1 greater t,an %I raising *urt,er -uestions about t,e .er 3ear, t,e nu+ber o* CVD e0ents .re/ e*5cac3 o* as.irin *or .ri+ar3 .re0ention 0ented 4ill be si+ilar to or greater t,an in .eo.le 4it, diabetes 7!%(,!%!9. t,e nu+ber o* e.isodes o* bleeding in/ duced, alt,oug, t,ese co+.lications do not ,a0e e-ual e**ects on long/ter+ ,ealt, 7!%:9.
Table %)dSu++ar3 o* reco++endations *or gl3ce+ic, blood .ressure, and li.id control *or +ost adults 4it, diabetes A%C Blood .ressure Li.ids LDL c,olesterol ,F.)IN ,%:)@E) ++DgNN ,%)) +g@dL 7,(." ++ol@L9T Statin t,era.3 *or t,ose 4it, ,istor3 o* ot,er ris1 *actors

at increased cardio0ascular ris1 7%)/ 3ear ris1 .%)I9. T,is includes +ost +en aged .H) 3ears or 4o+en aged .") 3ears 4,o ,a0e at least one additional +ajor ris1 *actor 7*a+il3 ,istor3 o* CVD, ,3.ertension, s+o1ing, d3sli.ide+ia, or albu+inuria9. 7C9 As.irin s,ould not be reco++ended *or CVD .re0ention *or adults 4it, diabetes at lo4 CVD ris1 7%)/3ear CVD ris1 ,HI, suc, as in +en aged ,H) 3ears and 4o+en aged ,") 3ears 4it, no +ajor additional CVD ris1 *actors9, since t,e .otential ad0erse e**ects *ro+ bleeding li1el3 o**set t,e .otential bene5ts. 7C9 In .atients in t,ese age/grou.s 4it, +ulti.le ot,er ris1 *actors 7e.g., %)/ 3ear ris1 H8%)I9, clinical judg+ent is re-uired. 7E9 Use as.irin t,era.3 7FH8%"( +g@da39 as a secondar3 .re0ention strateg3 in t,ose 4it, diabetes 4it, a ,istor3 o* CVD. 7A9 6or .atients 4it, CVD and docu/ +ented as.irin allerg3, clo.idogrel 7FH +g@da39 s,ould be used. 7B9 Co+bination t,era.3 4it, as.irin 7FH8 %"( +g@da39 and clo.idogrel 7FH +g@da39 is reasonable *or u. to a 3ear a*ter an acute coronar3 s3ndro+e. 7B9

In ()%), a .osition state+ent o* t,e ADA, t,e A+erican Deart Association 7ADA9, and t,e A+erican College o* Cardiolog3 6oundation 7ACC69 u.dated .rior joint reco++endations *or .ri+ar3 .re0ention 7!%H9. Lo4/dose 7FH8%"( +g@da39 as.irin use *or .ri+ar3 .re0en/ tion is reasonable *or adults 4it, diabetes and no .re0ious ,istor3 o* 0ascular dis/ ease 4,o are at increased CVD ris1 7%)/ 3ear ris1 o* CVD e0ents o0er %)I9 and 4,o are not at increased ris1 *or bleeding. T,is generall3 includes +ost +en o0er age H) 3ears and 4o+en o0er age ") 3ears 4,o also ,a0e one or +ore o* t,e *ollo4/ ing +ajor ris1 *actors> %9 s+o1ing, (9 ,3/ .ertension, !9 d3sli.ide+ia, :9 *a+il3 ,istor3 o* .re+ature CVD, and H9 albu/ +inuria. Do4e0er, as.irin is no longer reco+/ +ended *or t,ose at lo4 CVD ris1 74o+en under age ") 3ears and +en under age H) 3ears 4it, no +ajor CVD ris1 *actorsO %)/3ear CVD ris1 under HI9 as t,e lo4 bene5t is li1el3 to be out/ 4eig,ed b3 t,e ris1s o* signi5cant bleed/ ing. Clinical judg+ent s,ould be used *or t,ose at inter+ediate ris1 73ounger .a/ tients 4it, one or +ore ris1 *actors, or older .atients 4it, no ris1 *actorsO t,ose 4it, %)/3ear CVD ris1 o* H8%)I9 until *urt,er researc, is a0ailable. Use o* as.irin in .atients under t,e age o* (% 3ears is contraindicated due to t,e associated ris1 o* Re3e s3ndro+e. A0erage dail3 dosages used in +ost clinical trials in0ol0ing .atients 4it, di/ abetes ranged *ro+ H) to "H) +g but 4ere +ostl3 in t,e range o* %)) to !(H +g@da3. T,ere is little e0idence to su./ .ort an3 s.eci5c dose, but using t,e lo4est .ossible dosage +a3 ,el. reduce side e**ects 7!%"9. In t,e U.S., t,e +ost co++on lo4 dose tablet is E% +g. Al/ t,oug, .latelets *ro+ .atients 4it, dia/ betes ,a0e altered *unction, it is unclear 4,at, i* an3, i+.act t,at 5nding ,as on t,e re-uired dose o* as.irin *or cardio/
NNBased on .atient c,aracteristics and res.onse to t,era.3, lo4er s3stolic blood .ressure targets +a3 be a..ro.riate. TIn indi0iduals 4it, o0ert CVD, a lo4er LDL c,olesterol goal o* ,F) +g@dL 7%.E ++ol@L9, using a ,ig, dose o* a statin, is an o.tion.

I or age o0er :)%

N ore or less stringent gl3ce+ic goals +a3 be a..ro.riate *or indi0idual .atients. Coals s,ould be in/ di0iduali;ed based on duration o* diabetes, age@li*e e2.ectanc3, co+orbid conditions, 1no4n CVD or ad/ 0anced +icro0ascular co+.lications, ,3.ogl3ce+ia una4areness, and indi0idual .atient considerations.

.rotecti0e e**ects in t,e .atient 4it, di/ abetes. an3 alternate .at,4a3s *or .latelet acti0ation e2ist t,at are inde.en/ dent o* t,ro+bo2ane A( and t,us not sensiti0e to t,e e**ects o* as.irin 7!%F9. T,ere*ore, 4,ile =as.irin resistance? a./ .ears ,ig,er in t,e diabetic .atients 4,en +easured b3 a 0ariet3 o* e2 0i0o and in 0itro +et,ods 7.latelet aggrego+etr3, +easure+ent o* t,ro+bo2ane B(9, t,ese obser0ations alone are insu*5cient to e+/ .iricall3 reco++end ,ig,er doses o* as/ .irin be used in t,e diabetic .atient at t,is ti+e.

Clo.idogrel ,as been de+onstrated to reduce CVD e0ents in diabetic indi0id/ uals 7!%E9. It is reco++ended as adjunc/ ti0e t,era.3 in t,e 5rst 3ear a*ter an acute coronar3 s3ndro+e or as alternati0e t,er/ a.3 in as.irin/intolerant .atients. :. S+o1ing cessation Reco++endations c Ad0ise all .atients not to s+o1e or use tobacco .roducts. 7A9 c Include s+o1ing cessation counseling and ot,er *or+s o* treat+ent as a rou/ tine co+.onent o* diabetes care. 7B9 A large bod3 o* e0idence *ro+ e.ide/ +iological, case/control, and co,ort stud/ ies .ro0ides con0incing docu+entation o* t,e causal lin1 bet4een cigarette s+o1/ ing and ,ealt, ris1s. uc, o* t,e 4or1 docu+enting t,e i+.act o* s+o1ing on ,ealt, did not se.aratel3 discuss results on subsets o* indi0iduals 4it, diabetes, but suggests t,at t,e identi5ed ris1s are at least e-ui0alent to t,ose *ound in t,e general .o.ulation. Ot,er studies o* in/ di0iduals 4it, diabetes consistentl3 de+/ onstrate t,at s+o1ers ,a0e a ,eig,tened ris1 o* CVD, .re+ature deat,, and in/ creased rate o* +icro0ascular co+.lica/ tions o* diabetes. S+o1ing +a3 ,a0e a role in t,e de0elo.+ent o* t3.e ( diabetes. One stud3 in s+o1ers 4it, ne4l3 diag/ nosed t3.e ( diabetes *ound t,at s+o1ing cessation 4as associated 4it, a+elioration o* +etabolic .ara+eters and reduced blood .ressure and albu+inuria at % 3ear 7!%B9. T,e routine and t,oroug, assess+ent o* tobacco use is i+.ortant as a +eans o* .re0enting s+o1ing or encouraging ces/ sation. A nu+ber o* large rando+i;ed clinical trials ,a0e de+onstrated t,e e*5/ cac3 and cost/e**ecti0eness o* brie* coun/ seling in s+o1ing cessation, including t,e use o* -uitlines, in t,e reduction o* tobacco use. 6or t,e .atient +oti0ated to -uit, t,e addition o* .,ar+acological t,era.3 to counseling is +ore e**ecti0e t,an eit,er treat+ent alone. S.ecial con/ siderations s,ould include assess+ent o* le0el o* nicotine de.endence, 4,ic, is associated 4it, di*5cult3 in -uitting and rela.se 7!()9. H. CDD screening and treat+ent Reco++endations Screening c In as3+.to+atic .atients, routine screening *or CAD is not reco++ended, as it does not i+.ro0e outco+es as long

as CVD ris1 *actors are treated. 7A9

Treat+ent c In .atients 4it, 1no4n CVD, consider ACE in,ibitor t,era.3 7C9 and use as/ .irin and statin t,era.3 7A9 7i* not contraindicated9 to reduce t,e ris1 o* cardio0ascular e0ents. In .atients 4it, a .rior I, b/bloc1ers s,ould be contin/ ued *or at least ( 3ears a*ter t,e e0ent. 7B9 c A0oid t,ia;olidinedione treat+ent in .atients 4it, s3+.to+atic ,eart *ail/ ure. 7C9 c et*or+in +a3 be used in .atients 4it, stable CD6 i* renal *unction is nor+al. It s,ould be a0oided in unstable or ,os.itali;ed .atients 4it, CD6. 7C9 Screening *or CAD is re0ie4ed in a recentl3 u.dated consensus state+ent 7%B"9. To identi*3 t,e .resence o* CAD in diabetic .atients 4it,out clear or sug/ gesti0e s3+.to+s, a ris1 *actor8based a./ .roac, to t,e initial diagnostic e0aluation and subse-uent *ollo4/u. ,as intuiti0e a..eal. Do4e0er, recent studies con/ cluded t,at using t,is a..roac, *ails to identi*3 4,ic, .atients 4it, t3.e ( diabe/ tes 4ill ,a0e silent isc,e+ia on screening tests 7()%,!(%9. Candidates *or cardiac testing include t,ose 4it, %9 t3.ical or at3.ical cardiac s3+.to+s and (9 an abnor+al resting ECC. T,e screening o* as3+.to+atic .a/ tients re+ains contro0ersial. Intensi0e +edical t,era.3 t,at 4ould be indicated an34a3 *or diabetic .atients at ,ig, ris1 *or CVD see+s to .ro0ide e-ual outco+es to in0asi0e re0asculari;ation 7!((,!(!9. T,ere is also so+e e0idence t,at silent +3ocardial isc,e+ia +a3 re0erse o0er ti+e, adding to t,e contro0ers3 concern/ ing aggressi0e screening strategies 7!(:9. 6inall3, a recent rando+i;ed obser0a/ tional trial de+onstrated no clinical ben/ e5t to routine screening o* as3+.to+atic .atients 4it, t3.e ( diabetes and nor+al ECCs 7!(H9. Des.ite abnor+al +3ocar/ dial .er*usion i+aging in +ore t,an one in 50e .atients, cardiac outco+es 4ere essentiall3 e-ual 7and 0er3 lo49 in screened co+.ared 4it, unscreened .a/ tients. Accordingl3, t,e o0erall e**ecti0e/ ness, es.eciall3 t,e cost/e**ecti0eness, o* suc, an indiscri+inate screening strateg3 is no4 -uestioned. $e4er nonin0asi0e CAD screening +et,ods, suc, as co+.uted to+ogra.,3 7CT9 and CT angiogra.,3 ,a0e gained in .o.ularit3. T,ese tests in*er t,e .resence o* coronar3 at,erosclerosis b3 +easuring t,e a+ount o* calciu+ in coronar3 arter/ ies and, in so+e circu+stances, b3 direct 0isuali;ation o* lu+inal stenoses.

Alt,oug, as3+.to+atic diabetic .atients *ound to ,a0e a ,ig,er coronar3 disease burden ,a0e +ore *uture cardiac e0ents 7!("8!(E9, t,e role o* t,ese tests be3ond ris1 strati5cation is not clear. T,eir rou/ tine use leads to radiation e2.osure and +a3 result in unnecessar3 in0asi0e testing suc, as coronar3 angiogra.,3 and re0as/ culari;ation .rocedures. T,e ulti+ate balance o* bene5t, cost, and ris1s o* suc, an a..roac, in as3+.to+atic .a/ tients re+ains contro0ersial, .articularl3 in t,e +odern setting o* aggressi0e CVD ris1 *actor control. In all .atients 4it, diabetes, cardio/ 0ascular ris1 *actors s,ould be assessed at least annuall3. T,ese ris1 *actors include d3sli.ide+ia, ,3.ertension, s+o1ing, a .ositi0e *a+il3 ,istor3 o* .re+ature coronar3 disease, and t,e .resence o* +icro/ or +acroalbu/ +inuria. Abnor+al ris1 *actors s,ould be treated as described else4,ere in t,ese guidelines. #atients at increased CDD ris1 s,ould recei0e as.irin and a statin, and ACE in,ibitor or ARB t,era.3 i* ,3.ertensi0e, unless t,ere are contra/ indications to a .articular drug class. Alt,oug, clear bene5t e2ists *or ACE in,ibitor and ARB t,era.3 in .atients 4it, ne.,ro.at,3 or ,3.ertension, t,e bene5ts in .atients 4it, CVD in t,e absence o* t,ese conditions are less clear, es.eciall3 4,en LDL c,olesterol is con/ co+itantl3 controlled 7!(B,!!)9. B. $e.,ro.at,3 screening and treat+ent Reco++endations Ceneral reco++endations c To reduce t,e ris1 or slo4 t,e .rogres/ sion o* ne.,ro.at,3, o.ti+i;e glucose control. 7A9 c To reduce t,e ris1 or slo4 t,e .ro/ gression o* ne.,ro.at,3, o.ti+i;e blood .ressure control. 7A9 Screening c #er*or+ an annual test to assess urine albu+in e2cretion in t3.e % diabetic .atients 4it, diabetes duration o* JH 3ears and in all t3.e ( diabetic .atients starting at diagnosis. 7B9 c easure seru+ creatinine at least annuall3 in all adults 4it, diabetes regardless o* t,e degree o* urine albu+in e2cretion. T,e seru+ creatinine s,ould be used to esti/ +ate C6R and stage t,e le0el o* c,ronic 1idne3 disease 7CQD9, i* .resent. 7E9 Treat+ent c In t,e treat+ent o* t,e non.regnant

.atient 4it, +odestl3 ele0ated 7!)8 (BB

+g@da39 7C9 or ,ig,er le0els 7J!)) +g@da39 o* urinar3 albu+in e2cretion 7A9, eit,er ACE in,ibitors or ARBs are reco++ended. Reduction o* .rotein inta1e to ).E8%.) g@1g bod3 4t .er da3 in indi0iduals 4it, diabetes and t,e earlier stages o* CQD and to ).E g@1g bod3 4t .er da3 in t,e later stages o* CQD +a3 i+.ro0e +easures o* renal *unction 7urine al/ bu+in e2cretion rate, C6R9 and is reco++ended. 7C9 K,en ACE in,ibitors, ARBs, or diu/ retics are used, +onitor seru+ creati/ nine and .otassiu+ le0els *or t,e de0elo.+ent o* increased creatinine or c,anges in .otassiu+. 7E9 Continued +onitoring o* urine albu/ +in e2cretion to assess bot, res.onse to t,era.3 and .rogression o* disease is reasonable. 7E9 ( K,en eC6R ,") +L@+in@%.F! + , e0aluate and +anage .otential co+/ .lications o* CQD. 7E9 Consider re*erral to a .,3sician e2.e/ rienced in t,e care o* 1idne3 disease *or uncertaint3 about t,e etiolog3 o* 1id/ ne3 disease, di*5cult +anage+ent is/ sues, or ad0anced 1idne3 disease. 7B9

Diabetic ne.,ro.at,3 occurs in ()8:)I o* .atients 4it, diabetes and is t,e single leading cause o* ESRD. #ersistent albu/ +inuria in t,e range o* !)8(BB +g@(: , 7,istoricall3 called +icroalbu+inuria9 ,as been s,o4n to be t,e earliest stage o* diabetic ne.,ro.at,3 in t3.e % diabetes and a +ar1er *or de0elo.+ent o* ne.,ro./ at,3 in t3.e ( diabetes. It is also a 4ell/ establis,ed +ar1er o* increased CVD ris1 7!!%,!!(9. #atients 4it, +icroalbu+inuria 4,o .rogress to +ore signi5cant le0els 7J!)) +g@(: ,, ,istoricall3 called +ac/ roalbu+inuria9 are li1el3 to .rogress to ESRD 7!!!,!!:9. Do4e0er, a nu+ber o* inter0entions ,a0e been de+onstrated to reduce t,e ris1 and slo4 t,e .rogression o* renal disease. Intensi0e diabetes +anage+ent 4it, t,e goal o* ac,ie0ing near/ nor+ogl3ce+ia ,as been s,o4n in large .ros.ecti0e ran/ do+i;ed studies to dela3 t,e onset and .rogression o* increased urinar3 albu+in e2cretion in .atients 4it, t3.e % 7!!H,!!"9 and t3.e ( 7E!,E:,EE,EB9 dia/ betes. T,e UQ#DS .ro0ided strong e0i/ dence t,at control o* blood .ressure can reduce t,e de0elo.+ent o* ne.,ro.at,3 7(HH9. In addition, large .ros.ecti0e ran/ do+i;ed

studies in .atients 4it, t3.e % diabetes .ressure 7,%:) ++Dg9 resulting *ro+ ,a0e de+onstrated t,at ac,ie0e/ +ent treat+ent using ACE in,ibitors .ro0ides a o* lo4er le0els o* s3stolic blood selecti0e bene5t o0er ot,er anti,3.erten/ si0e drug classes in dela3ing t,e .rogres/ sion o* increased urinar3 albu+in e2cretion and can slo4 t,e decline in C6R in .atients 4it, ,ig,er le0els o* albu+inuria 7!!F8 !!B9. In t3.e ( diabetes 4it, ,3.ertension and nor+oalbu+inuria, RAS in,ibition ,as been de+onstrated to dela3 onset o* +icroalbu+inuria 7!:),!:%9. In t,e latter stud3, t,ere 4as an une2.ected ,ig,er rate o* *atal cardio0ascular e0ents 4it, ol+esar/ tan a+ong .atients 4it, .ree2isting CDD. ACE in,ibitors ,a0e been s,o4n to reduce +ajor CVD outco+es 7i.e., I, stro1e, deat,9 in .atients 4it, diabetes 7(F)9, t,us *urt,er su..orting t,e use o* t,ese agents in .atients 4it, albu+inuria, a CVD ris1 *actor. ARBs do not .re0ent onset o* albu+inuria in nor+otensi0e .atients 4it, t3.e % or t3.e ( diabetes 7!:(,!:!9O ,o4e0er, ARBs ,a0e been s,o4n to reduce t,e rate o* .rogression *ro+ +icro/ to +ac/ roalbu+inuria as 4ell as ESRD in .atients 4it, t3.e ( diabetes 7!::8!:"9. So+e e0/ idence suggests t,at ARBs ,a0e a s+aller +agnitude o* rise in .otassiu+ co+.ared 4it, ACE in,ibitors in .eo.le 4it, ne/ .,ro.at,3 7!:F,!:E9. Co+binations o* drugs t,at bloc1 t,e renin/angiotensin/ aldosterone s3ste+ 7e.g., an ACE in,ibitor .lus an ARB, a +ineralocorticoid antago/ nist, or a direct renin in,ibitor9 .ro0ide additional lo4ering o* albu+inuria 7!:B8 !H(9. Do4e0er, suc, co+binations ,a0e been *ound to .ro0ide no additional car/ dio0ascular bene5t and ,a0e ,ig,er ad/ 0erse e0ent rates 7!H!9, and t,eir e**ects on +ajor renal outco+es ,a0e not 3et been .ro0en. Ot,er drugs, suc, as diuretics, cal/ ciu+ c,annel bloc1ers, and b/bloc1ers, s,ould be used as additional t,era.3 to *urt,er lo4er blood .ressure in .atients alread3 treated 4it, ACE in,ibitors or ARBs 7(FH9, or as alternate t,era.3 in t,e rare indi0idual unable to tolerate ACE in,ibitors or ARBs. Studies in .atients 4it, 0ar3ing stages o* ne.,ro.at,3 ,a0e s,o4n t,at .rotein restriction o* dietar3 .rotein ,el.s slo4 t,e .rogression o* albu+inuria, C6R de/ cline, and occurrence o* ESRD 7!H:8 !HF9, alt,oug, +ore recent studies ,a0e .ro0ided conAicting results 7%:)9. Die/ tar3 .rotein restriction +ig,t be consid/ ered .articularl3 in .atients 4,ose ne.,ro.at,3 see+s to be .rogressing de/ s.ite o.ti+al glucose and blood .ressure control and use o* ACE in,ibitor and@or ARBs 7!HF9.

Assess+ent o* albu+inuria status and renal *unction Screening *or increased urinar3 albu+in e2cretion can be .er*or+ed b3 +easure/ +ent o* t,e albu+in/to/creatinine ratio in a rando+ s.ot collectionO (:/, or ti+ed collections are +ore burdenso+e and add little to .rediction or accurac3 7!HE,!HB9. easure+ent o* a s.ot urine *or albu+in onl3, 4,et,er b3 i++unoas/ sa3 or b3 using a di.stic1 test s.eci5c *or +icroalbu+in, 4it,out si+ultaneousl3 +easuring urine creatinine, is so+e4,at less e2.ensi0e but susce.tible to *alse/ negati0e and *alse/.ositi0e deter+ina/ tions as a result o* 0ariation in urine concentration due to ,3dration and ot,er *actors. Abnor+alities o* albu+in e2cretion and t,e lin1age bet4een albu+in/to/ creatinine ratio and (:/, albu+in e2cre/ tion are de5ned in Table %%. Because o* 0ariabilit3 in urinar3 albu+in e2cretion, t4o o* t,ree s.eci+ens collected 4it,in a !/ to "/+ont, .eriod s,ould be abnor+al be*ore considering a .atient to ,a0e de/ 0elo.ed increased urinar3 albu+in e2cre/ tion or ,ad a .rogression in albu+inuria. E2ercise 4it,in (: ,, in*ection, *e0er, CD6, +ar1ed ,3.ergl3ce+ia, and +ar1ed ,3.ertension +a3 ele0ate urinar3 albu+in e2cretion o0er baseline 0alues. In*or+ation on .resence o* abnor+al urine albu+in e2cretion in addition to le0el o* C6R +a3 be used to stage CQD. T,e $ational Qidne3 6oundation classi5/ cation 7Table %(9 is .ri+aril3 based on C6R le0els and t,ere*ore di**ers *ro+ ot,er s3ste+s, in 4,ic, staging is based .ri+aril3 on urinar3 albu+in e2cretion 7!")9. Studies ,a0e *ound decreased C6R in t,e absence o* increased urine al/ bu+in e2cretion in a substantial .ercent/ age o* adults 4it, diabetes 7!"%9. Seru+ creatinine s,ould t,ere*ore be +easured at least annuall3 in all adults 4it,

NDistoricall3, ratios bet4een !) and (BB ,a0e been called +icroalbu+inuria and t,ose !)) or greater ,a0e been called +acroalbu+inuria 7or clinical al/ bu+inuria9.

Table %%dDe5nitions o* abnor+alities in albu+in e2cretion S.ot collection 7 +g @+g c re a ,!) J!)

Ca teg or 3 ti ni ne 9 $or+al Increased urinar3 albu+in e2cretionN

diabetes, regardless o* t,e degree o* urine albu+in e2cretion. Seru+ creatinine s,ould be used to esti+ate C6R and to stage t,e le0el o* CQD, i* .resent. eC6R is co++onl3 core.orted b3 laboratories or can be esti+ated using *or+ulae suc, as t,e odi5cation o* Diet in Renal Disease 7 DRD9 stud3 e-uation 7!"(9. Recent re/ .orts ,a0e indicated t,at t,e DRD is +ore accurate *or t,e diagnosis and strat/ i5cation o* CQD in .atients 4it, diabetes t,an t,e Coc1cro*t/Cault *or+ula 7!"!9. C6R calculators are a0ailable at ,tt.>@@ 444.n1de..ni,.go0. T,e role o* continued annual -uanti/ tati0e assess+ent o* albu+in e2cretion a*ter diagnosis o* albu+inuria and insti/ tution o* ACE in,ibitor or ARB t,era.3 and blood .ressure control is unclear. Continued sur0eillance can assess bot, res.onse to t,era.3 and .rogression o* disease. So+e suggest t,at reducing al/ bu+inuria to t,e nor+al 7,!) +g@g9 or near/nor+al range +a3 i+.ro0e renal and cardio0ascular .rognosis, but t,is a./ .roac, ,as not been *or+all3 e0aluated in .ros.ecti0e trials. Co+.lications o* 1idne3 disease cor/ relate 4it, le0el o* 1idne3 *unction. ( K,en t,e eC6R is ,") +L@+in@%.F! + , screen/ ing *or co+.lications o* CQD is indicated 7Table %!9. Earl3 0accination against ,e.a/ titis B is indicated in .atients li1el3 to .rog/ ress to end/stage 1idne3 disease. Consider re*erral to a .,3sician e2.e/ rienced in t,e care o* 1idne3 disease 4,en t,ere is uncertaint3 about t,e etiolog3 o* 1idne3 disease 7,ea03 .roteinuria, acti0e urine sedi+ent, absence o* retino.at,3, ra.id decline in C6R, resistant ,3.erten/ sion9. Ot,er triggers *or re*erral +a3 in/ clude di*5cult +anage+ent issues 7ane+ia, secondar3 ,3.er.arat,3roidis+, +etabolic bone disease, or electrol3te disturbance9 or ad0anced 1idne3 disease. T,e t,res,old *or re*erral +a3 0ar3 de.ending on t,e *re/ -uenc3 4it, 4,ic, a .ro0ider encounters diabetic .atients 4it, signi5cant 1idne3

disease. Consultation 4it, a ne.,rologist 4,en stage : CQD de0elo.s ,as been *ound to reduce cost, i+.ro0e -ualit3 o* care, and 1ee. .eo.le o** dial3sis longer 7!":9. Do4/ e0er, nonrenal s.ecialists s,ould not dela3 educating t,eir .atients about t,e .rogres/ si0e nature o* diabetic 1idne3 diseaseO t,e renal .reser0ation bene5ts o* aggressi0e treat+ent o* blood .ressure, blood glucose, and ,3.erli.ide+iaO and t,e .otential need *or renal re.lace+ent t,era.3. C. Retino.at,3 screening and treat+ent Reco++endations Ceneral reco++endations c To reduce t,e ris1 or slo4 t,e .ro/ gression o* retino.at,3, o.ti+i;e gl3/ ce+ic control. 7A9 c To reduce t,e ris1 or slo4 t,e .ro/ gression o* retino.at,3, o.ti+i;e blood .ressure control. 7A9 Screening c Adults and c,ildren aged J%) 3ears 4it, t3.e % diabetes s,ould ,a0e an initial dilated and co+.re,ensi0e e3e e2a+ination b3 an o.,t,al+ologist or o.to+etrist 4it,in H 3ears a*ter t,e onset o* diabetes. 7B9 c #atients 4it, t3.e ( diabetes s,ould ,a0e an initial dilated and co+.re/ ,ensi0e e3e e2a+ination b3 an o.,/ t,al+ologist or o.to+etrist s,ortl3 a*ter t,e diagnosis o* diabetes. 7B9 c Subse-uent e2a+inations *or t3.e % and t3.e ( diabetic .atients s,ould be re.eated annuall3 b3 an o.,t,al+ologist or o.to+etrist. Less *re-uent e2a+s 7e0er3 (8! 3ears9 +a3 be considered *ollo4ing one or +ore nor+al e3e e2a+s. E2a+inations 4ill be re-uired +ore *re/ -uentl3 i* retino.at,3 is .rogressing. 7B9 c Dig,/-ualit3 *undus .,otogra.,s can detect +ost clinicall3 signi5cant di/ abetic retino.at,3. Inter.retation o* t,e i+ages s,ould be .er*or+ed b3 a trained e3e care .ro0ider. K,ile retinal .,otogra.,3 +a3 ser0e as a screening tool *or retino.at,3, it is not a substitute
C6R 7+L@+in@%.F! +(

*or a co+.re,ensi0e e3e e2a+, 4,ic, s,ould be .er*or+ed at least initiall3 and at inter0als t,erea*ter as reco+/ +ended b3 an e3e care .ro*essional. 7E9 c Ko+en 4it, .re/e2isting diabetes 4,o are .lanning .regnanc3 or 4,o ,a0e beco+e .regnant s,ould ,a0e a co+/ .re,ensi0e e3e e2a+ination and be counseled on t,e ris1 o* de0elo.+ent and@or .rogression o* diabetic reti/ no.at,3. E3e e2a+ination s,ould oc/ cur in t,e 5rst tri+ester 4it, close *ollo4/u. t,roug,out .regnanc3 and *or % 3ear .ost.artu+. 7B9 Treat+ent c #ro+.tl3 re*er .atients 4it, an3 le0el o* +acular ede+a, se0ere $#DR, or an3 #DR to an o.,t,al+ologist 4,o is 1no4ledgeable and e2.erienced in t,e +anage+ent and treat+ent o* diabetic retino.at,3. 7A9 c Laser .,otocoagulation t,era.3 is in/ dicated to reduce t,e ris1 o* 0ision loss in .atients 4it, ,ig,/ris1 #DR, clini/ call3 signi5cant +acular ede+a, and in so+e cases o* se0ere $#DR. 7A9 c Anti80ascular endot,elial gro4t, *ac/ tor 7VEC69 t,era.3 is indicated *or di/ abetic +acular ede+a. 7A9 c T,e .resence o* retino.at,3 is not a contraindication to as.irin t,era.3 *or cardio.rotection, as t,is t,era.3 does not increase t,e ris1 o* retinal ,e+or/ r,age. 7A9 Diabetic retino.at,3 is a ,ig,l3 s.eci5c 0ascular co+.lication o* bot, t3.e % and t3.e ( diabetes, 4it, .re0alence strongl3 related to t,e duration o* diabetes. Di/ abetic retino.at,3 is t,e +ost *re-uent cause o* ne4 cases o* blindness a+ong adults aged ()8F: 3ears. Clauco+a, cata/ racts, and ot,er disorders o* t,e e3e occur earlier and +ore *re-uentl3 in .eo.le 4it, diabetes. In addition to duration o* diabetes, ot,er *actors t,at increase t,e ris1 o*, or are associated 4it,, retino.at,3 include c,ronic ,3.ergl3ce+ia 7!"H9, ne.,ro./ at,3 7!""9, and ,3.ertension 7!"F9. In/ tensi0e diabetes +anage+ent 4it, t,e goal o* ac,ie0ing near/ nor+ogl3ce+ia ,as been s,o4n in large .ros.ecti0e ran/ do+i;ed studies to .re0ent and@or dela3 t,e onset and .rogression o* diabetic ret/
: %H8(B Se0erel3 decreased C6R

Table %( dStages o* CQD

Stage % ( !

Descri.tion Qidne3 da+ageN 4it, nor+al or increased C6R Qidne3 da+ageN 4it, +ildl3 decreased C6R oderatel3 decreased C6R

bod3 sur*ace area9 JB) ")8EB !)8HB

H di al 3s is

Q i dne 3 * ai lu r e

, % H or

NQidne3 da+age de5ned as abnor+alities on .at,ological, urine, blood, or i+aging tests. Ada.ted *ro+ re*. !HB.

ino.at,3 7F%,E!,E:,B)9. Lo4ering blood .ressure ,as been s,o4n to decrease t,e .rogression o* retino.at,3 7(HH9, al/ t,oug, tig,t targets 7s3stolic ,%() ++Dg9 do not i+.art additional bene5t 7B)9. Se0eral case series and a controlled .ros.ecti0e stud3 suggest t,at .regnanc3

Table %!d anage+ent o* CQD in diabetes C6R All .atients :H8") Reco++ended 'earl3 +easure+ent o* creatinine, urinar3 albu+in e2cretion, .otassiu+ Re*erral to ne.,rolog3 i* .ossibilit3 *or nondiabetic 1idne3 disease e2ists 7duration o* t3.e % diabetes ,%) 3ears, ,ea03 .roteinuria, abnor+al 5ndings on renal ultrasound, resistant ,3.ertension, ra.id *all in C6R, or acti0e urinar3 sedi+ent on ultrasound9 Consider need *or dose adjust+ent o* +edications onitor eC6R e0er3 " +ont,s onitor electrol3tes, bicarbonate, ,e+oglobin, calciu+, .,os.,orus, .arat,3roid ,or+one at least 3earl3 Assure 0ita+in D su*5cienc3 Consider bone densit3 testing Re*erral *or dietar3 counseling onitor eC6R e0er3 ! +ont,s onitor electrol3tes, bicarbonate, calciu+, .,os.,orus, .arat,3roid ,or+one, ,e+oglobin, albu+in, 4eig,t e0er3 !8" +ont,s Consider need *or dose adjust+ent o* +edications Re*erral to ne.,rologist

!)8::

,!)

Ada.ted *ro+ ,tt.>@@444.1idne3.org@.ro*essionals@QDOPI@guidelineWdiabetes@.

ris1 o* de0elo.+ent o* signi5cant retino./ at,3 4it, a !/3ear inter0al a*ter a nor+al e2a+ination 7!F"9. E2a+inations 4ill be re-uired +ore *re-uentl3 i* retino.at,3 is .rogressing 7!FF9. T,e use o* retinal .,otogra.,3 4it, re+ote reading b3 e2.erts ,as great .o/ tential in areas 4,ere -uali5ed e3e care .ro*essionals are not a0ailable and +a3 also en,ance e*5cienc3 and reduce costs 4,en t,e e2.ertise o* o.,t,al+ologists can be utili;ed *or +ore co+.le2 e2a+i/ nations and *or t,era.3 7!FE9. In/.erson e2a+s are still necessar3 4,en t,e .,otos are unacce.table and *or *ollo4/u. o* ab/ nor+alities detected. #,otos are not a substitute *or a co+.re,ensi0e e3e e2a+, 4,ic, s,ould be .er*or+ed at least initiall3 and at inter0als t,erea*ter as rec/ o++ended b3 an e3e care .ro*essional. Results o* e3e e2a+inations s,ould be docu+ented and trans+itted to t,e re*er/ ring ,ealt, care .ro*essional. acuit3. Reco+binant +onoclonal neutral/ i;ing antibod3 to VEC6 is a ne4l3 a./ .ro0ed t,era.3 t,at i+.ro0es 0ision and reduces t,e need *or laser .,otocoa/ gulation in .atients 4it, +acular ede+a 7!F(9. Ot,er e+erging t,era.ies *or reti/ no.at,3 include sustained intra0itreal de/ li0er3 o* Auocinolone 7!F!9 and t,e .ossibilit3 o* .re0ention 4it, *eno5brate 7!F:,!FH9. T,e .re0enti0e e**ects o* t,era.3 and t,e *act t,at .atients 4it, #DR or +acular ede+a +a3 be as3+.to+atic .ro0ide strong su..ort *or a screening .rogra+ to detect diabetic retino.at,3. As retino./ at,3 is esti+ated to ta1e at least H 3ears to de0elo. a*ter t,e onset o* ,3.ergl3ce+ia, .atients 4it, t3.e % diabetes s,ould ,a0e an initial dilated and co+.re,ensi0e e3e e2a+ination 4it,in H 3ears a*ter t,e onset o* diabetes. #atients 4it, t3.e ( diabetes, 4,o generall3 ,a0e ,ad 3ears o* undiag/ nosed diabetes and 4,o ,a0e a signi5cant ris1 o* .re0alent diabetic retino.at,3 at ti+e o* diabetes diagnosis, s,ould ,a0e an initial dilated and co+.re,ensi0e e3e e2a+/ ination soon a*ter diagnosis. E2a+inations s,ould be .er*or+ed b3 an o.,t,al+ologist or o.to+etrist 4,o is 1no4ledgeable and e2.erienced in diagnosing t,e .resence o* diabetic retino.at,3 and is a4are o* its +anage+ent. Subse-uent e2a+inations *or t3.e % and t3.e ( diabetic .atients are generall3 re.eated annuall3. Less *re-uent e2a+s 7e0er3 (8! 3ears9 +a3 be cost e**ec/ ti0e a*ter one or +ore nor+al e3e e2a+s, and in a .o.ulation 4it, 4ell/controlled t3.e ( diabetes t,ere 4as essentiall3 no

in t3.e % diabetic .atients +a3 aggra0ate retino.at,3 7!"E,!"B9O laser .,otocoa/ gulation surger3 can +ini+i;e t,is ris1 7!"B9. One o* t,e +ain +oti0ations *or screening *or diabetic retino.at,3 is t,e long/establis,ed e*5cac3 o* laser .,oto/ coagulation surger3 in .re0enting 0isual loss. T4o large trials, t,e Diabetic Reti/ no.at,3 Stud3 7DRS9 in .atients 4it, #DR and t,e Earl3 Treat+ent Diabetic Retino.at,3 Stud3 7ETDRS9 in .atients 4it, +acular ede+a, .ro0ide t,e stron/ gest su..ort *or t,e t,era.eutic bene5ts o* .,otocoagulation surger3. T,e DRS 7!F)9 s,o4ed t,at .anretinal .,otocoag/ ulation surger3 reduced t,e ris1 o* se0ere 0ision loss *ro+ #DR *ro+ %H.BI in un/ treated e3es to ".:I in treated e3es, 4it, greatest ris1/bene5t ratio in t,ose 4it, baseline disease 7disc neo0asculari;ation or 0itreous ,e+orr,age9. T,e ETDRS 7!F%9 establis,ed t,e bene5t o* *ocal laser .,otocoagulation surger3 in e3es 4it, +acular ede+a, .ar/ ticularl3 t,ose 4it, clinicall3 signi5cant +acular ede+a, 4it, reduction o* dou/ bling o* t,e 0isual angle 7e.g., ()@H) to ()@%))9 *ro+ ()I in untreated e3es to EI in treated e3es. T,e ETDRS also 0eri/ 5ed t,e bene5ts o* .anretinal .,otocoag/ ulation *or ,ig,/ris1 #DR and in older/ onset .atients 4it, se0ere $#DR or less/ t,an/,ig,/ris1 #DR. Laser .,otocoagulation surger3 in bot, trials 4as bene5cial in reducing t,e

ris1 o* *urt,er 0isual loss, but generall3 not bene5cial in re0ersing alread3 di+inis,ed

D. $euro.at,3 screening and treat+ent Reco++endations c All .atients s,ould be screened *or distal s3++etric .ol3neuro.at,3 7D#$9 start/ ing at diagnosis o* t3.e ( diabetes and H 3ears a*ter t,e diagnosis o* t3.e % diabetes and at least annuall3 t,erea*ter, using si+.le clinical tests. 7B9 c Electro.,3siological testing is rarel3 needed, e2ce.t in situations 4,ere t,e clinical *eatures are at3.ical. 7E9 c Screening *or signs and s3+.to+s o* cardio0ascular autono+ic neuro.at,3 7CA$9 s,ould be instituted at diagnosis o* t3.e ( diabetes and H 3ears a*ter t,e diagnosis o* t3.e % diabetes. S.ecial testing is rarel3 needed and +a3 not a**ect +anage+ent or outco+es. 7E9 c edications *or t,e relie* o* s.eci5c s3+.to+s related to .ain*ul D#$ and autono+ic neuro.at,3 are reco+/ +ended, as t,e3 i+.ro0e t,e -ualit3 o* li*e o* t,e .atient. 7E9 T,e diabetic neuro.at,ies are ,etero/ geneous 4it, di0erse clinical +ani*esta/ tions. T,e3 +a3 be *ocal or di**use. ost co++on a+ong t,e neuro.at,ies are c,ronic sensori+otor D#$ and autono+ic neuro.at,3. Alt,oug, D#$ is a diagnosis o* e2clusion, co+.le2 in0estigations to e2clude ot,er conditions are rarel3 needed. T,e earl3 recognition and a..ro.ri/ ate +anage+ent o* neuro.at,3 in t,e .atient 4it, diabetes is i+.ortant *or a nu+ber o* reasons> %9 nondiabetic

neuro.at,ies +a3 be .resent in .atients 4it, diabetes and +a3 be treatableO (9 a nu+ber o* treat+ent o.tions e2ist *or s3+.to+atic diabetic neuro.at,3O !9 u. to H)I o* D#$ +a3 be as3+.to+atic and .atients are at ris1 *or insensate injur3 to t,eir *eetO and :9 autono+ic neuro.at,3, and .articularl3 CA$, is associated 4it, substantial +orbidit3 and e0en +ortalit3. S.eci5c treat+ent *or t,e underl3ing ner0e da+age is currentl3 not a0ailable, ot,er t,an i+.ro0ed gl3ce+ic control, 4,ic, +a3 +odestl3 slo4 .rogression 7EB9 but not re0erse neuronal loss. E**ec/ ti0e s3+.to+atic treat+ents are a0ailable *or so+e +ani*estations o* D#$ 7!FB9 and autono+ic neuro.at,3. Diagnosis o* neuro.at,3 D#$. #atients 4it, diabetes s,ould be screened annuall3 *or D#$ using tests suc, as .in.ric1 sensation, 0ibration .er/ ce.tion 7using a %(E/D; tuning *or19, %)/g +ono5la+ent .ressure sensation at t,e distal .lantar as.ect o* bot, great toes and +etatarsal joints, and assess+ent o* an1le reAe2es. Co+binations o* +ore t,an one test ,a0e .EFI sensiti0it3 in detecting D#$. Loss o* %)/g +ono5la+ent .erce./ tion and reduced 0ibration .erce.tion .redict *oot ulcers 7!E)9. I+.ortantl3, in .atients 4it, neuro.at,3, .articularl3 4,en se0ere, causes ot,er t,an diabetes s,ould al4a3s be considered, suc, as neu/ roto2ic +edications, ,ea03 +etal .oison/ ing, alco,ol abuse, 0ita+in B%( de5cienc3 7es.eciall3 in t,ose ta1ing +et*or+in *or .rolonged .eriods 7!E%9, renal disease, c,ronic inAa++ator3 de+3elinating neu/ ro.at,3, in,erited neuro.at,ies, and 0as/ culitis 7!E(9. Diabetic autono+ic neuro.at,3. T,e s3+.to+s and signs o* autono+ic d3s/ *unction s,ould be elicited care*ull3 dur/ ing t,e ,istor3 and .,3sical e2a+ination. ajor clinical +ani*estations o* diabetic autono+ic neuro.at,3 include resting tac,3cardia, e2ercise intolerance, ort,o/ static ,3.otension, consti.ation, gastro/ .aresis, erectile d3s*unction, sudo+otor d3s*unction, i+.aired neuro0ascular *unc/ tion, and, .otentiall3, autono+ic *ailure in res.onse to ,3.ogl3ce+ia 7!E!9. CA$, a CVD ris1 *actor 7B!9, is t,e +ost studied and clinicall3 i+.ortant *or+ o* diabetic autono+ic neuro.at,3.

CA$ +a3 be indicated b3 resting tac,3/ cardia 7.%)) b.+9, ort,ostasis 7a *all in s3stolic blood .ressure .() ++Dg u.on standing 4it,out an a..ro.riate ,eart rate res.onse9O it is also associated 4it, increased cardiac e0ent rates. Alt,oug,

so+e societies ,a0e de0elo.ed guidelines *or screening *or CA$, t,e bene5ts o* so/ .,isticated testing be3ond ris1 strati5ca/ tion are not clear 7!E:9. Castrointestinal neuro.at,ies 7e.g., eso.,ageal entero.at,3, gastro.aresis, consti.ation, diarr,ea, *ecal inconti/ nence9 are co++on, and an3 section o* t,e gastrointestinal tract +a3 be a**ected. Castro.aresis s,ould be sus.ected in in/ di0iduals 4it, erratic glucose control or 4it, u..er gastrointestinal s3+.to+s 4it,out ot,er identi5ed cause. E0alua/ tion o* solid/.,ase gastric e+.t3ing using double/isoto.e scintigra.,3 +a3 be done i* s3+.to+s are suggesti0e, but test re/ sults o*ten correlate .oorl3 4it, s3+./ to+s. Consti.ation is t,e +ost co++on lo4er/gastrointestinal s3+.to+ but can alternate 4it, e.isodes o* diarr,ea. Diabetic autono+ic neuro.at,3 is also associated 4it, genitourinar3 tract disturbances. In +en, diabetic autono+ic neuro.at,3 +a3 cause erectile d3s*unc/ tion and@or retrograde ejaculation. E0al/ uation o* bladder d3s*unction s,ould be .er*or+ed *or indi0iduals 4it, diabetes 4,o ,a0e recurrent urinar3 tract in*ec/ tions, .3elone.,ritis, incontinence, or a .al.able bladder. S3+.to+atic treat+ents D#$. T,e 5rst ste. in +anage+ent o* .atients 4it, D#$ s,ould be to ai+ *or stable and o.ti+al gl3ce+ic control. Al/ t,oug, controlled trial e0idence is lac1/ ing, se0eral obser0ational studies suggest t,at neuro.at,ic s3+.to+s i+.ro0e not onl3 4it, o.ti+i;ation o* control, but also 4it, t,e a0oidance o* e2tre+e blood glucose Auctuations. #atients 4it, .ain*ul D#$ +a3 bene5t *ro+ .,ar+acological treat+ent o* t,eir s3+.to+s> +an3 agents ,a0e con5r+ed or .robable e*5/ cac3 con5r+ed in s3ste+atic re0ie4s o* RCTs 7!FB9, 4it, se0eral U.S. 6ood and Drug Ad+inistration 76DA9/a..ro0ed *or t,e +anage+ent o* .ain*ul D#$. Treat+ent o* autono+ic neuro.at,3. Castro.aresis s3+.to+s +a3 i+.ro0e 4it, dietar3 c,anges and .ro1inetic agents suc, as +etoclo.ra+ide or er3t,/ ro+3cin. Treat+ents *or erectile d3s*unc/ tion +a3 include .,os.,odiesterase t3.e H in,ibitors, intracor.oreal or intraure/ t,ral .rostaglandins, 0acuu+ de0ices, or .enile .rost,eses. Inter0entions *or ot,er +ani*estations o* autono+ic neuro.at,3 are described in t,e ADA state+ent on neuro.at,3 7!E)9. As 4it, D#$ treat/ +ents, t,ese inter0entions do not c,ange t,e underl3ing .at,olog3 and natural

,istor3 o* t,e disease .rocess, but +a3 ,a0e a .ositi0e i+.act on t,e -ualit3 o* li*e o* t,e .atient. E. 6oot care Reco++endations c 6or all .atients 4it, diabetes, .er*or+ an annual co+.re,ensi0e *oot e2a+i/ nation to identi*3 ris1 *actors .redicti0e o* ulcers and a+.utations. T,e *oot e2a+ination s,ould include ins.ection, assess+ent o* *oot .ulses, and testing *or loss o* .rotecti0e sensation 7LO#S9 7%)/g +ono5la+ent .lus testing an3 one o* t,e *ollo4ing> 0ibration using %(E/D; tuning *or1, .in.ric1 sensation, an1le reAe2es, or 0ibration .erce.tion t,res,/ old9. 7B9 c #ro0ide general *oot sel*/care education to all .atients 4it, diabetes. 7B9 c A +ultidisci.linar3 a..roac, is rec/ o++ended *or indi0iduals 4it, *oot ulcers and ,ig,/ris1 *eet, es.eciall3 t,ose 4it, a ,istor3 o* .rior ulcer or a+.utation. 7B9 c Re*er .atients 4,o s+o1e, ,a0e LO#S and structural abnor+alities, or ,a0e ,istor3 o* .rior lo4er/e2tre+it3 co+/ .lications to *oot care s.ecialists *or ongoing .re0enti0e care and li*elong sur0eillance. 7C9 c Initial screening *or .eri.,eral arterial disease 7#AD9 s,ould include a ,istor3 *or claudication and an assess+ent o* t,e .edal .ulses. Consider obtaining an an1le/brac,ial inde2 7ABI9, as +an3 .atients 4it, #AD are as3+.to+/ atic. 7C9 c Re*er .atients 4it, signi5cant claudi/ cation or a .ositi0e ABI *or *urt,er 0ascular assess+ent and consider e2/ ercise, +edications, and surgical o./ tions. 7C9 A+.utation and *oot ulceration, con/ se-uences o* diabetic neuro.at,3 and@or #AD, are co++on and +ajor causes o* +orbidit3 and disabilit3 in .eo.le 4it, diabetes. Earl3 recognition and +anage/ +ent o* ris1 *actors can .re0ent or dela3 ad0erse outco+es. T,e ris1 o* ulcers or a+.utations is increased in .eo.le 4,o ,a0e t,e *ollo4/ ing ris1 *actors>
c c c c c c

#re0ious a+.utation #ast *oot ulcer ,istor3 #eri.,eral neuro.at,3 6oot de*or+it3 #eri.,eral 0ascular disease Visual i+.air+ent

,o4e0er, identi5cation o* t,e .atient 4it, LO#S can easil3 be carried out 4it,out c t,is or ot,er e2.ensi0e e-ui.+ent. c Initial screening *or #AD s,ould include a ,istor3 *or claudication and an assess+ent o* t,e .edal .ulses. A diag/ an3 studies ,a0e been .ublis,ed nostic ABI s,ould be .er*or+ed in an3 .ro.osing a range o* tests t,at +ig,t .atient 4it, s3+.to+s o* #AD. Due to use*ull3 identi*3 .atients at ris1 *or *oot t,e ,ig, esti+ated .re0alence o* #AD in ulceration, creating con*usion a+ong .atients 4it, diabetes and t,e *act t,at .ractitioners as to 4,ic, screening tests +an3 .atients 4it, #AD are as3+.to+/ s,ould be ado.ted in clinical .ractice. An atic, an ADA consensus state+ent on ADA tas1 *orce 4as t,ere*ore asse+bled #AD 7!E"9 suggested t,at a screening in ())E to concisel3 su++ari;e recent ABI be .er*or+ed in .atients o0er H) literature in t,is area and t,en 3ears o* age and be considered in reco++end 4,at s,ould be included in .atients under H) t,e co+.re/ ,ensi0e *oot e2a+ *or adult .atients 4it, diabetes. T,eir 3ears o* age 4,o ,a0e ot,er #AD ris1 *ac/ reco++endations are su+/ +ari;ed tors 7e.g., s+o1ing, ,3.ertension, ,3.er/ belo4, but clinicians s,ould re*er to t,e li.ide+ia, or duration o* diabetes .%) tas1 *orce re.ort 7!EH9 *or *urt,er details 3ears9. Re*er .atients 4it, signi5cant and .ractical descri.tions o* ,o4 to s3+.to+s or a .ositi0e ABI *or *urt,er .er*or+ co+.onents o* t,e co+.re,en/ 0ascular assess+ent and consider e2er/ cise, +edications, and surgical o.tions si0e *oot e2a+ination. At least annuall3, all adults 4it, di/ 7!E"9. #atients 4it, diabetes and ,ig,/ris1 abetes s,ould undergo a co+.re,ensi0e *oot e2a+ination to identi*3 ,ig,/ris1 *oot conditions s,ould be educated re/ conditions. Clinicians s,ould as1 about garding t,eir ris1 *actors and a..ro.riate ,istor3 o* .re0ious *oot ulceration or +anage+ent. #atients at ris1 s,ould un/ a+.utation, neuro.at,ic or .eri.,eral derstand t,e i+.lications o* t,e loss o* 0ascular s3+.to+s, i+.aired 0ision, to/ .rotecti0e sensation, t,e i+.ortance o* bacco use, and *oot care .ractices. A *oot +onitoring on a dail3 basis, t,e general ins.ection o* s1in integrit3 and .ro.er care o* t,e *oot, including nail +usculos1eletal de*or+ities s,ould be and s1in care, and t,e selection o* a..ro/ done in a 4ell/lit roo+. Vascular assess/ .riate *oot4ear. #atients 4it, LO#S +ent 4ould include ins.ection and as/ s,ould be educated on 4a3s to substitute ot,er sensor3 +odalities 7,and .al.ation, sess+ent o* .edal .ulses. T,e neurologic e2a+ reco++ended 0isual ins.ection9 *or sur0eillance o* earl3 is designed to identi*3 LO#S rat,er t,an *oot .roble+s. T,e .atients< understand/ earl3 neuro.at,3. T,e clinical e2a+ina/ ing o* t,ese issues and t,eir .,3sical tion to identi*3 LO#S is si+.le and abil/ re-uires no e2.ensi0e e-ui.+ent. 6i0e it3 to conduct .ro.er *oot sur0eillance si+.le clinical tests 7use o* a %)/g +ono/ and care s,ould be assessed. #atients 5la+ent, 0ibration testing using a %(E/D; 4it, 0isual di*5culties, .,3sical con/ tuning *or1, tests o* .in.ric1 sensation, straints .re0enting +o0e+ent, or cogni/ an1le reAe2 assess+ent, and testing 0i/ ti0e .roble+s t,at i+.air t,eir abilit3 to bration .erce.tion t,res,old 4it, a bio/ assess t,e condition o* t,e *oot and to in/ t,esio+eter9, eac, 4it, e0idence *ro+ stitute a..ro.riate res.onses 4ill need 4ell/conducted .ros.ecti0e clinical co/ ot,er .eo.le, suc, as *a+il3 +e+bers, ,ort studies, are considered use*ul in t,e to assist in t,eir care. #eo.le 4it, neuro.at,3 or e0idence diagnosis o* LO#S in t,e diabetic *oot. T,e tas1 *orce agrees t,at an3 o* t,e 50e o* increased .lantar .ressure 7e.g., er3/ tests listed could be used b3 clinicians to t,e+a, 4ar+t,, callus, or +easured identi*3 LO#S, alt,oug, ideall3 t4o o* .ressure9 +a3 be ade-uatel3 +anaged t,ese s,ould be regularl3 .er*or+ed dur/ 4it, 4ell/5tted 4al1ing s,oes or at,letic ing t,e screening e2a+dnor+all3 t,e s,oes t,at cus,ion t,e *eet and redistrib/ %)/g +ono5la+ent and one ot,er test. ute .ressure. Callus can be debrided One or +ore abnor+al tests 4ould sug/ 4it, a scal.el b3 a *oot care s.ecialist gest LO#S, 4,ile at least t4o nor+al or ot,er ,ealt, .ro*essional 4it, e2.eri/ tests 7and no abnor+al test9 4ould rule ence and training in *oot care. #eo.le out LO#S. T,e last test listed, 4it, bon3 de*or+ities 7e.g., ,a++er/ toes, .ro+inent +etatarsal ,eads, bun/ 0ibration as/ sess+ent using a biot,esio+eter or ions9 +a3 need e2tra/4ide or /de.t, si+i/ lar instru+ent, is 4idel3 used in s,oes. #eo.le 4it, e2tre+e bon3 de*or+ities 7e.g., C,arcot *oot9 4,o t,e U.S.O

Diabetic ne.,ro.at,3 7es.eciall3 .a/ tients on dial3sis9 #oor gl3ce+ic control Cigarette s+o1ing

cannot be acco++odated 4it, co++ercial t,era.eutic *oot4ear +a3 need custo+/ +olded s,oes. 6oot ulcers and 4ound care +a3 re-uire care b3 a .odiatrist, ort,o.edic or 0ascular surgeon, or re,abilitation s.ecialist e2.erienced in t,e +anage+ent o* indi0iduals 4it, diabetes. Cuidelines *or treat+ent o* diabetic *oot ulcers ,a0e recentl3 been u.dated 7!EF9. VII. ASSESS E$T O6 CO O$ CO ORBID CO$DITIO$S Reco++endations c 6or .atients 4it, ris1 *actors, signs or s3+.to+s, consider assess+ent and treat+ent *or co++on diabetes/ asso/ ciated conditions 7see Table %:9. 7B9 In addition to t,e co++onl3 a..re/ ciated co+orbidities o* obesit3, ,3.erten/ sion, and d3sli.ide+ia, diabetes is also associated 4it, ot,er diseases or condi/ tions at rates ,ig,er t,an t,ose o* age/ +atc,ed .eo.le 4it,out diabetes. A *e4 o* t,e +ore co++on co+orbidities are described ,erein and listed in Table %:. Dearing i+.air+ent Dearing i+.air+ent, bot, ,ig, *re-uenc3 and lo4@+id *re-uenc3, is +ore co++on in .eo.le 4it, diabetes, .er,a.s due to neuro.at,3 and@or 0ascular disease. In an $DA$ES anal3sis, ,earing i+.air+ent 4as about t4ice as great in .eo.le 4it, diabetes co+.ared 4it, t,ose 4it,out, a*ter adjusting *or age and ot,er ris1 *actors *or ,earing i+.air+ent 7!EE9. Controlling *or age, race, and ot,er de+o/ gra.,ic *actors, ,ig, *re-uenc3 loss in t,ose 4it, diabetes 4as signi5cantl3 asso/ ciated 4it, ,istor3 o* CDD and 4it, .e/ ri.,eral neuro.at,3, 4,ile lo4@+id *re-uenc3 loss 4as associated 4it, lo4 DDL c,olesterol and 4it, .oor re.orted ,ealt, status 7!EB9.

Table %:dCo++on co+orbidities *or 4,ic, increased ris1 is associated 4it, diabetes Dearing i+.air+ent Obstructi0e slee. a.nea 6att3 li0er disease Lo4 testosterone in +en #eriodontal disease Certain cancers 6ractures Cogniti0e i+.air+ent De .r e ss io n

Obstructi0e slee. a.nea Age/adjusted rates o* obstructi0e slee. a.nea, a ris1 *actor *or CVD, are signi5/ cantl3 ,ig,er 7:/ to %)/*old9 4it, obesit3, es.eciall3 4it, central obesit3, in +en and 4o+en 7!B)9. T,e .re0alence in gen/ eral .o.ulations 4it, t3.e ( diabetes +a3 be u. to (!I 7!B%9, and in obese .artic/ i.ants enrolled in t,e Loo1 ADEAD trial e2ceeded E)I 7!B(9. Treat+ent o* slee. a.nea signi5cantl3 i+.ro0es -ualit3 o* li*e and blood .ressure control. T,e e0i/ dence *or a treat+ent e**ect on gl3ce+ic control is +i2ed 7!B!9. 6att3 li0er disease Une2.lained ele0ation o* ,e.atic trans/ a+inase concentrations is signi5cantl3 associated 4it, ,ig,er B I, 4aist circu+/ *erence, trigl3cerides, and *asting insulin, and 4it, lo4er DDL c,olesterol. T3.e ( diabetes and ,3.ertension are inde.en/ dentl3 associated 4it, transa+inase ele/ 0ations in 4o+en 7!B:9. In a .ros.ecti0e anal3sis, diabetes 4as signi5cantl3 associ/ ated 4it, incident nonalco,olic c,ronic li0er disease and 4it, ,e.atocellular car/ cino+a 7!BH9. Inter0entions t,at i+.ro0e +etabolic abnor+alities in .atients 4it, diabetes 74eig,t loss, gl3ce+ic control, treat+ent 4it, s.eci5c drugs *or ,3.er/ gl3ce+ia or d3sli.ide+ia9 are also bene5/ cial *or *att3 li0er disease 7!B"9. Lo4 testosterone in +en ean le0els o* testosterone are lo4er in +en 4it, diabetes co+.ared 4it, age/ +atc,ed +en 4it,out diabetes, but obesit3 is a +ajor con*ounder 7!BF9. T,e issue o* treat+ent in as3+.to+atic +en is contro0ersial. T,e e0idence *or e**ects o* tes/ tosterone re.lace+ent on outco+es is +i2ed, and recent guidelines suggest t,at screening and treat+ent o* +en 4it,out s3+.to+s are not reco++ended 7!BE9.

signi5cant ).:FI i+.ro0e+ent in A%C, but noted +ulti.le .roble+s 4it, t,e -ual/ it3 o* t,e .ublis,ed studies included in t,e

anal3sis 7:))9. Se0eral ,ig,/-ualit3 RCTs ,a0e not s,o4n a signi5cant e**ect 7:)%9. Cancer Diabetes 7.ossibl3 onl3 t3.e ( diabetes9 is associated 4it, increased ris1 o* cancers o* t,e li0er, .ancreas, endo+etriu+, co/ lon@rectu+, breast, and bladder 7:)(9. T,e association +a3 result *ro+ s,ared ris1 *actors bet4een t3.e ( diabetes and cancer 7obesit3, age, and .,3sical inacti0/ it39 but +a3 also be due to ,3.erinsuline/ +ia or ,3.ergl3ce+ia 7:)%,:)!9. #atients 4it, diabetes s,ould be encouraged to undergo reco++ended age/ and se2/ a..ro.riate cancer screenings and to re/ duce t,eir +odi5able cancer ris1 *actors 7obesit3, s+o1ing, and .,3sical inacti0it39. 6ractures Age/+atc,ed ,i. *racture ris1 is signi5/ cantl3 increased in bot, t3.e % 7su++ar3 RR ".!9 and t3.e ( diabetes 7su++ar3 RR %.F9 in bot, se2es 7:):9. T3.e % diabetes is associated 4it, osteo.orosis, but in t3.e ( diabetes an increased ris1 o* ,i. *racture is seen des.ite ,ig,er bone +in/ eral densit3 7B D9 7:)H9. One stud3 s,o4ed t,at .re0alent 0ertebral *ractures 4ere signi5cantl3 +ore co++on in +en and 4o+en 4it, t3.e ( diabetes, but 4ere not associated 4it, B D 7:)"9. In t,ree large obser0ational studies o* older adults, *e+oral nec1 B D T/score and t,e KDO *racture ris1 algorit,+ 76RAU9 score 4ere associated 4it, ,i. and nons.ine *racture, alt,oug, *racture ris1 4as ,ig,er in diabetic .artici.ants co+.ared 4it, .artici.ants 4it,out dia/ betes *or a gi0en T/score and age or *or a gi0en 6RAU score ris1 7:)F9. It is a..ro/ .riate to assess *racture ,istor3 and ris1 *actors in older .atients 4it, diabetes and reco++end B D testing i* a..ro.riate *or t,e .atient<s age and se2. 6or at/ris1 .atients, it is reasonable to consider stan/ dard .ri+ar3 or secondar3 .re0ention strategies 7reduce ris1 *actors *or *alls, en/ sure ade-uate calciu+ and 0ita+in D in/ ta1e, a0oid use o* +edications t,at lo4er B D, suc, as glucocorticoids9, and to con/ sider .,ar+acot,era.3 *or ,ig,/ris1 .a/ tients. 6or .atients 4it, t3.e ( diabetes 4it, *racture ris1 *actors, a0oiding use o* t,ia;olidinediones is 4arranted. Cogniti0e i+.air+ent Diabetes is associated 4it, signi5cantl3 increased ris1 o* cogniti0e decline, a greater rate o* cogniti0e decline, and increased ris1 o* de+entia 7:)E,:)B9. In a %H/3ear .ros.ecti0e stud3 o* a
care.diabetesjournals.org

#eriodontal disease #eriodontal disease is +ore se0ere, but not necessaril3 +ore .re0alent, in .a/ tients 4it, diabetes t,an t,ose 4it,out 7!BB9. $u+erous studies ,a0e suggested associations 4it, .oor gl3ce+ic control, ne.,ro.at,3, and CVD, but +ost studies are ,ig,l3 con*ounded. A co+.re,ensi0e assess+ent, and treat+ent o* identi5ed disease, is indicated in .atients 4it, dia/ betes, but t,e e0idence t,at .eriodontal disease treat+ent i+.ro0es gl3ce+ic con/ trol is +i2ed. AC+eta/anal3sis re.orted S: DIABETES ARE, VOLU E !", S U##LE E$Ta %, &A$UAR' ()%!
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co++unit3/d4elling .eo.le o0er t,e age o* ") 3ears, t,e .resence o* diabetes at baseline signi5cantl3 increased t,e age/ and se2/adjusted incidence o* all/cause de+entia, Al;,ei+er disease, and 0ascu/ lar de+entia co+.ared 4it, rates in t,ose 4it, nor+al glucose tolerance 7:%)9. In a substud3 o* t,e ACCORD stud3, t,ere 4ere no di**erences in cogniti0e outco+es bet4een intensi0e and standard gl3ce+ic control, alt,oug, t,ere 4as signi5cantl3 less o* a decre+ent in total brain 0olu+e b3 +agnetic resonance i+aging in .artic/ i.ants in t,e intensi0e ar+ 7:%%9. T,e e*/ *ects o* ,3.ergl3ce+ia and insulin on t,e brain are areas o* intense researc, interest. De.ression As discussed in Section V.D, de.ression is ,ig,l3 .re0alent in .eo.le 4it, diabetes and is associated 4it, 4orse outco+es. VIII. DIABETES CARE I$ S#ECI6IC #O#ULATIO$S A. C,ildren and adolescents Reco++endations c As is t,e case *or all c,ildren, c,ildren 4it, diabetes or .rediabetes s,ould be encouraged to engage in at least ") +in o* .,3sical acti0it3 eac, da3. 7B9 %. T3.e % diabetes T,ree/-uarters o* all cases o* t3.e % di/ abetes are diagnosed in indi0iduals ,%E 3ears o* age. It is a..ro.riate to consider t,e uni-ue as.ects o* care and +anage/ +ent o* c,ildren and adolescents 4it, t3.e % diabetes. C,ildren 4it, diabetes di**er *ro+ adults in +an3 res.ects, in/ cluding c,anges in insulin sensiti0it3 re/ lated to se2ual +aturit3 and .,3sical gro4t,, abilit3 to .ro0ide sel*/care, su.er/ 0ision in c,ild care and sc,ool, and uni-ue neurologic 0ulnerabilit3 to ,3.o/ gl3ce+ia and DQA. Attention to suc, is/ sues as *a+il3 d3na+ics, de0elo.+ental stages, and .,3siological di**erences re/ lated to se2ual +aturit3 are all essential in de0elo.ing and i+.le+enting an o.ti/ +al diabetes regi+en. Alt,oug, reco+/ +endations *or c,ildren and adolescents are less li1el3 to be based on clinical trial e0idence, e2.ert o.inion and a re0ie4 o* a0ailable and rele0ant e2.eri+ental data are su++ari;ed in t,e ADA state+ent on care o* c,ildren and adolescents 4it, t3.e % diabetes 7:%(9. Ideall3, t,e care o* a c,ild or adoles/ cent 4it, t3.e % diabetes s,ould be .ro/ 0ided b3 a +ultidisci.linar3 tea+ o* s.ecialists trained in t,e care o* c,ildren
care.diabetesjournals.org DIABETES CARE,
VOLU E

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%, &A$UAR' ()%!

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4it, .ediatric diabetes. At t,e 0er3 least, education o* t,e c,ild and *a+il3 s,ould be .ro0ided b3 ,ealt, care .ro0iders trained and e2.erienced in c,ild,ood diabetes and sensiti0e to t,e c,allenges .osed b3 diabetes in t,is age/grou.. It is essential t,at DS E, $T, and .s3c,o/ social su..ort be .ro0ided at t,e ti+e o* diagnosis and regularl3 t,erea*ter b3 in/ di0iduals e2.erienced 4it, t,e educational, nutritional, be,a0ioral, and e+otional needs o* t,e gro4ing c,ild and *a+il3. It is e2.ected t,at t,e balance bet4een adult su.er0ision and sel*/care s,ould be de5ned and t,at it 4ill e0ol0e 4it, .,3sical, .s3/ c,ological, and e+otional +aturit3. a. Cl3ce+ic control Reco++endations c Consider age 4,en setting gl3ce+ic goals in c,ildren and adolescents 4it, t3.e % diabetes. 7E9 K,ile current standards *or diabetes +anage+ent reAect t,e need to lo4er glucose as sa*el3 .ossible, s.ecial consid/ eration s,ould be gi0en to t,e uni-ue ris1s o* ,3.ogl3ce+ia in 3oung c,ildren. Cl3ce+ic goals +a3 need to be +odi5ed to ta1e into account t,e *act t,at +ost c,ildren ," or F 3ears o* age ,a0e a *or+ o* =,3.ogl3ce+ic una4areness,? includ/ ing i++aturit3 and a relati0e inabilit3 to recogni;e and res.ond to ,3.ogl3ce+ic s3+.to+s, .lacing t,e+ at greater ris1 *or se0ere ,3.ogl3ce+ia and its se-uelae. In addition, and unli1e t,e case in t3.e % diabetic adults, 3oung c,ildren belo4 t,e age o* H 3ears +a3 be at ris1 *or .er+a/ nent cogniti0e i+.air+ent a*ter e.isodes o* se0ere ,3.ogl3ce+ia 7:%!8:%H9. 6ur/ t,er+ore, t,e DCCT de+onstrated t,at near/nor+ali;ation o* blood glucose le0/ els 4as +ore di*5cult to ac,ie0e in ado/ lescents t,an adults. $e0ert,eless, t,e increased *re-uenc3 o* use o* basal/bolus regi+ens and insulin .u+.s in 3out, *ro+ in*anc3 t,roug, adolescence ,as been associated 4it, +ore c,ildren reac,ing ADA blood glucose targets 7:%",:%F9 in t,ose *a+ilies in 4,ic, bot, .arents and t,e c,ild 4it, diabetes .artici.ate jointl3 to .er*or+ t,e re/ -uired diabetes/related tas1s. 6urt,er/ +ore, recent studies docu+enting neurocogniti0e se-uelae o* ,3.ergl3ce/ +ia in c,ildren .ro0ide anot,er co+.el/ ling +oti0ation *or ac,ie0ing gl3ce+ic targets 7:%E,:%B9. In selecting gl3ce+ic goals, t,e bene/ 5ts on long/ter+ ,ealt, outco+es o* ac,ie0ing a lo4er A%C s,ould be

balanced

against t,e ris1s o* ,3.ogl3ce+ia and t,e de0elo.+ental burdens o* intensi0e regi/ +ens in c,ildren and 3out,. Age/s.eci5c gl3ce+ic and A%C goals are .resented in Table %H. b. Screening and +anage+ent o* c,ronic co+.lications in c,ildren and adolescents 4it, t3.e % diabetes i. $e.,ro.at,3 Reco++endations c Annual screening *or +icroalbu+inuria, 4it, a rando+ s.ot urine sa+.le *or albu+in/to/creatinine ratio, s,ould be considered once t,e c,ild is %) 3ears o* age and ,as ,ad diabetes *or H 3ears. 7B9 c Treat+ent 4it, an ACE in,ibitor, ti/ trated to nor+ali;ation o* albu+in e2/ cretion, s,ould be considered 4,en ele0ated albu+in/to/creatinine ratio is subse-uentl3 con5r+ed on t4o addi/ tional s.eci+ens *ro+ di**erent da3s. 7E9 ii. D3.ertension Reco++endations c Blood .ressure s,ould be +easured at eac, routine 0isit. C,ildren *ound to ,a0e ,ig,/nor+al blood .ressure or ,3.ertension s,ould ,a0e blood .res/ sure con5r+ed on a se.arate da3. 7B9 c Initial treat+ent o* ,ig,/nor+al blood .ressure 7s3stolic or diastolic blood .res/ sure consistentl3 abo0e t,e B)t, .ercen/ tile *or age, se2, and ,eig,t9 includes dietar3 inter0ention and e2ercise, ai+ed at 4eig,t control and increased .,3sical acti0it3, i* a..ro.riate. I* target blood .ressure is not reac,ed 4it, !8" +ont,s o* li*est3le inter0ention, .,ar+acological treat+ent s,ould be considered. 7E9 c #,ar+acological treat+ent o* ,3.erten/ sion 7s3stolic or diastolic blood .ressure consistentl3 abo0e t,e BHt, .ercentile *or age, se2, and ,eig,t or consistentl3 .%!)@E) ++Dg, i* BHI e2ceeds t,at 0alue9 s,ould be considered as soon as t,e diagnosis is con5r+ed. 7E9 c ACE in,ibitors s,ould be considered *or t,e initial treat+ent o* ,3.ertension, *ollo4ing a..ro.riate re.roducti0e counseling due to its .otential terato/ genic e**ects. 7E9 c T,e goal o* treat+ent is a blood .res/ sure consistentl3 ,%!)@E) or belo4 t,e B)t, .ercentile *or age, se2, and ,eig,t, 4,ic,e0er is lo4er. 7E9 It is i+.ortant t,at blood .ressure +easure+ents are deter+ined correctl3, using t,e a..ro.riate si;e cu**, and 4it, t,e c,ild seated and rela2ed. D3.ertension

s,ould be con5r+ed on at least t,ree se.arate da3s. $or+al blood .ressure le0els *or age, se2, and ,eig,t and a..ro/ .riate +et,ods *or deter+inations are a0ailable online at 444.n,lbi.ni,.g o0@ ,ealt,@.ro*@,eart@,b.@,b.W.ed..d*. iii. D3sli.ide+ia Reco++endations Screening c I* t,ere is a *a+il3 ,istor3 o* ,3.erc,o/ lesterole+ia or a cardio0ascular e0ent be*ore age HH 3ears, or i* *a+il3 ,istor3 is un1no4n, t,en consider obtaining a *asting li.id .ro5le on c,ildren .( 3ears o* age soon a*ter diagnosis 7a*ter glucose control ,as been establis,ed9. I* *a+il3 ,istor3 is not o* concern, t,en consider t,e 5rst li.id screening at .ubert3 7J%) 3ears o* age9. 6or c,ildren diagnosed 4it, diabetes at or a*ter .ubert3, con/ sider obtaining a *asting li.id .ro5le soon a*ter t,e diagnosis 7a*ter glucose control ,as been establis,ed9. 7E9 c 6or bot, age/grou.s, i* li.ids are ab/ nor+al, annual +onitoring is reason/ able. I* LDL c,olesterol 0alues are 4it,in t,e acce.ted ris1 le0els 7,%)) +g@dL L(." ++ol@LM9, a li.id .ro5le re.eated e0er3 H 3ears is reasonable. 7E9 Treat+ent c Initial t,era.3 +a3 consist o* o.ti+i/ ;ation o* glucose control and $T using a Ste. ( ADA diet ai+ed at a decrease in t,e a+ount o* saturated *at in t,e diet. 7E9 c A*ter t,e age o* %) 3ears, t,e addition o* a statin in .atients 4,o, a*ter $T and li*est3le c,anges, ,a0e LDL c,oles/ terol .%") +g@dL 7:.% ++ol@L9, or LDL c,olesterol .%!) +g@dL 7!.: ++ol@L9 and one or +ore CVD ris1 *actors, is reasonable. 7E9 c T,e goal o* t,era.3 is an LDL c,oles/ terol 0alue ,%)) +g@dL 7(." ++ol@L9. 7E9 #eo.le diagnosed 4it, t3.e % diabetes in c,ild,ood ,a0e a ,ig, ris1 o* earl3 subclinical 7:()8:((9 and clinical 7:(!9 CVD. Alt,oug, inter0ention data are lac1ing, t,e ADA categori;es c,ildren 4it, t3.e % diabetes in t,e ,ig,est tier *or cardio0ascular ris1 and reco++ends bot, li*est3le and .,ar+acological treat/

+ent *or t,ose 4it, ele0ated LDL c,oles/ terol le0els 7:(:,:(H9. Initial t,era.3 s,ould be 4it, a Ste. ( ADA diet, 4,ic, restricts saturated *at to FI o* total calo/ ries and restricts dietar3 c,olesterol to ()) +g@da3. Data *ro+ rando+i;ed clin/ ical trials in c,ildren as 3oung as F +ont,s o* age indicate t,at t,is diet is sa*e and

Table %Hd#las+a blood glucose and A%C goals *or t3.e % diabetes b3 age/grou. #las+a blood glucose goal range 7+g@dL9 Values b3 age 73ears9 Toddlers and .resc,oolers 7)8"9 Be*ore +eals %))8%E) Bedti+e@ o0ernig,t %%)8()) A%C ,E.HI
c c

Rationale Vulnerabilit3 to ,3.ogl3ce+ia Insulin sensiti0it3 c Un.redictabilit3 in dietar3 inta1e and .,3sical acti0it3 c A lo4er goal 7,E.)I9 is reasonable i* it can be ac,ie0ed 4it,out e2cessi0e ,3.ogl3ce+ia c Vulnerabilit3 o* ,3.ogl3ce+ia c A lo4er goal 7,F.HI9 is reasonable i* it can be ac,ie0ed 4it,out e2cessi0e ,3.ogl3ce+ia c A lo4er goal 7,F.)I9 is reasonable i* it can be ac,ie0ed 4it,out e2cessi0e ,3.ogl3ce+ia

Sc,ool age 7"8%(9

B)8%E)

%))8%E)

,EI

Adolescents and 3oung adults 7%!8%B9

B)8%!)

B)8%H)

,F.HI

Qe3 conce.ts in setting gl3ce+ic goals> Coals s,ould be indi0iduali;ed and lo4er goals +a3 be reasonable based on bene5t/ris1 assess+ent. c Blood glucose goals s,ould be +odi5ed in c,ildren 4it, *re-uent ,3.ogl3ce+ia or ,3.ogl3ce+ia una4areness. c #ost.randial blood glucose 0alues s,ould be +easured 4,en t,ere is a discre.anc3 bet4een .re.randial blood glucose 0alues and A%C le0els and to ,el. assess gl3ce+ia in t,ose on basal@bolus regi+ens.
c

does not inter*ere 4it, nor+al gro4t, and de0elo.+ent 7:(",:(F9. $eit,er long/ter+ sa*et3 nor cardio/ 0ascular outco+e e*5cac3 o* statin t,era.3 ,as been establis,ed *or c,ildren. Do4/ e0er, recent studies ,a0e s,o4n s,ort/ ter+ sa*et3 e-ui0alent to t,at seen in adults and e*5cac3 in lo4ering LDL c,olesterol le0els, i+.ro0ing endot,elial *unction and caus/ ing regression o* carotid inti+al t,ic1ening 7:(E8:!)9. $o statin is a..ro0ed *or use under t,e age o* %) 3ears, and statin treat/ +ent s,ould generall3 not be used in c,il/ dren 4it, t3.e % diabetes .rior to t,is age. 6or .ost.ubertal girls, issues o* .regnanc3 .re0ention are .ara+ount, since statins are categor3 U in .regnanc3. See Section VIII.B *or +ore in*or+ation. i0. Retino.at,3 Reco++endations c T,e 5rst o.,t,al+ologic e2a+ination s,ould be obtained once t,e c,ild is J%) 3ears o* age and ,as ,ad diabetes *or !8H 3ears. 7B9 c A*ter t,e initial e2a+ination, annual routine *ollo4/u. is generall3 reco+/ +ended. Less *re-uent e2a+inations +a3 be acce.table on t,e ad0ice o* an e3e care .ro*essional. 7E9 Alt,oug, retino.at,3 7li1e albu+inuria9 +ost co++onl3 occurs a*ter t,e onset o* .ubert3 and a*ter H8%) 3ears o* diabetes duration 7:!%9, it ,as been re.orted in

.re.ubertal c,ildren and 4it, diabetes duration o* onl3 %8( 3ears. Re*errals

s,ould be +ade to e3e care .ro*essionals 4it, e2.ertise in diabetic retino.at,3, an understanding o* t,e ris1 *or retino.at,3 in t,e .ediatric .o.ulation, and e2.eri/ ence in counseling t,e .ediatric .atient and *a+il3 on t,e i+.ortance o* earl3 .re/ 0ention@inter0ention. 0. Celiac disease Reco++endations c Consider screening c,ildren 4it, t3.e % diabetes *or celiac disease b3 +easuring tissue transgluta+inase or antiendo+3sial antibodies, 4it, docu+entation o* nor/ +al total seru+ IgA le0els, soon a*ter t,e diagnosis o* diabetes. 7E9 c Testing s,ould be considered in c,il/ dren 4it, gro4t, *ailure, *ailure to gain 4eig,t, 4eig,t loss, diarr,ea, Aatulence, abdo+inal .ain, or signs o* +alabsor./ tion or in c,ildren 4it, *re-uent un/ e2.lained ,3.ogl3ce+ia or deterioration in gl3ce+ic control. 7E9 c Consider re*erral to a gastroenterolo/ gist *or e0aluation 4it, .ossible en/ dosco.3 and bio.s3 *or con5r+ation o* celiac disease in as3+.to+atic c,ildren 4it, .ositi0e antibodies. 7E9 c C,ildren 4it, bio.s3/con5r+ed celiac disease s,ould be .laced on a gluten/ *ree diet and ,a0e consultation 4it, a dietitian e2.erienced in +anaging bot, diabetes and celiac disease. 7B9 Celiac disease is an i++une/+ediated dis/ order t,at occurs 4it, increased *re-uenc3 in .atients 4it, t3.e % diabetes 7%8%"I o*

indi0iduals co+.ared 4it, ).!8%I in t,e general .o.ulation9 7:!(,:!!9. S3+.to+s o* celiac disease include diarr,ea, 4eig,t loss or .oor 4eig,t gain, gro4t, *ailure, abdo+inal .ain, c,ronic *atigue, +alnutri/ tion due to +alabsor.tion, and ot,er gastrointestinal .roble+s, and une2.lained ,3.ogl3ce+ia or erratic blood glucose con/ centrations. Screening *or celiac disease includes +easuring seru+ le0els o* tissue trans/ gluta+inase or antiendo+3sial antibodies, t,en s+all bo4el bio.s3 in antibod3/ .ositi0e c,ildren. Recent Euro.ean guide/ lines on screening *or celiac disease in c,ildren 7not s.eci5c to c,ildren 4it, t3.e % diabetes9 suggested t,at bio.s3 +ig,t not be necessar3 in s3+.to+atic c,ildren 4it, .ositi0e antibodies, as long as *urt,er testing suc, as genetic or DLA testing 4as su..orti0e, but t,at as3+.to+atic but at/ ris1 c,ildren s,ould ,a0e bio.sies 7:!:9. One s+all stud3 t,at included c,ildren 4it, and 4it,out t3.e % diabetes sugges/ ted t,at antibod3/.ositi0e but bio.s3/neg/ ati0e c,ildren 4ere si+ilar clinicall3 to t,ose 4,o 4ere bio.s3 .ositi0e and t,at bio.s3/negati0e c,ildren ,ad bene5ts *ro+ a gluten/*ree diet but 4orsening on a usual diet 7:!H9. Because t,is stud3 4as s+all and because c,ildren 4it, t3.e % di/ abetes alread3 need to *ollo4 a care*ul diet, it is di*5cult to ad0ocate *or not con5r+ing t,e diagnosis b3 bio.s3 be*ore reco++end/ ing a li*elong gluten/*ree diet, es.eciall3 in as3+.to+atic c,ildren. In s3+.to+atic c,ildren 4it, t3.e % diabetes and celiac

disease, gluten/*ree diets reduce s3+.to+s and rates o* ,3.ogl3ce+ia 7:!"9. 0i. D3.ot,3roidis+ Reco++endations c Consider screening c,ildren 4it, t3.e % diabetes *or t,3roid .ero2idase and t,3roglobulin antibodies soon a*ter diagnosis. 7E9 c easuring t,3roid/sti+ulating ,or/ +one 7TSD9 concentrations soon a*ter diagnosis o* t3.e % diabetes, a*ter +e/ tabolic control ,as been establis,ed, is reasonable. I* nor+al, consider re/ c,ec1ing e0er3 %8( 3ears, es.eciall3 i* t,e .atient de0elo.s s3+.to+s o* t,3/ roid d3s*unction, t,3ro+egal3, or an abnor+al gro4t, rate. 7E9 Autoi++une t,3roid disease is t,e +ost co++on autoi++une disorder associ/ ated 4it, diabetes, occurring in %F8!)I o* .atients 4it, t3.e % diabetes 7:!F9. About one/-uarter o* t3.e % diabetic c,il/ dren ,a0e t,3roid autoantibodies at t,e ti+e o* diagnosis o* t,eir diabetes 7:!E9, and t,e .resence o* t,3roid autoantibod/ ies is .redicti0e o* t,3roid d3s*unction, generall3 ,3.ot,3roidis+ but less co+/ +onl3 ,3.ert,3roidis+ 7:!B9. Subclini/ cal ,3.ot,3roidis+ +a3 be associated 4it, increased ris1 o* s3+.to+atic ,3.o/ gl3ce+ia 7::)9 and 4it, reduced linear gro4t, 7::%9. D3.ert,3roidis+ alters glucose +etabolis+, .otentiall3 resulting in deterioration o* +etabolic control. c. Sel*/+anage+ent $o +atter ,o4 sound t,e +edical regi/ +en, it can onl3 be as good as t,e abilit3 o* t,e *a+il3 and@or indi0idual to i+.le/ +ent it. 6a+il3 in0ol0e+ent in diabetes re+ains an i+.ortant co+.onent o* o.ti/ +al diabetes +anage+ent t,roug,out c,ild,ood and adolescence. Dealt, care .ro0iders 4,o care *or c,ildren and adoles/ cents, t,ere*ore, +ust be ca.able o* e0aluating t,e educational, be,a0ioral, e+o/ tional, and .s3c,osocial *actors t,at i+.act i+.le+entation o* a treat+ent .lan and +ust 4or1 4it, t,e indi0idual and *a+il3 to o0erco+e barriers or rede5ne goals as a./ .ro.riate. d. Sc,ool and da3 care Since a si;able .ortion o* a c,ild<s da3 is s.ent in sc,ool, close co++unication 4it, and coo.eration o* sc,ool or da3 care .ersonnel is essential *or o.ti+al di/

abetes +anage+ent, sa*et3, and +a2i+al acade+ic o..ortunities. See t,e ADA .o/ sition state+ent on diabetes care in t,e

sc,ool and da3 care setting 7::(9 *or *ur/ t,er discussion. e. Transition *ro+ .ediatric to adult care Reco++endations c As teens transition into e+erging adult,ood, ,ealt, care .ro0iders and *a+ilies +ust recogni;e t,eir +an3 0ulnerabilities 7B9 and .re.are t,e de/ 0elo.ing teen, beginning in earl3 to +id adolescence and at least % 3ear .rior to t,e transition. 7E9 c Bot, .ediatricians and adult ,ealt, care .ro0iders s,ould assist in .ro/ 0iding su..ort and lin1s to resources *or t,e teen and e+erging adult. 7B9 Care and close su.er0ision o* diabetes +anage+ent is increasingl3 s,i*ted *ro+ .arents and ot,er older adults t,roug,/ out c,ild,ood and adolescence. Do4/ e0er, t,e s,i*t *ro+ .ediatrics to adult ,ealt, care .ro0iders o*ten occurs 0er3 abru.tl3 as t,e older teen enters t,e ne2t de0elo.+ental stage re*erred to as e+erg/ ing adult,ood 7::!9, a critical .eriod *or 3oung .eo.le 4,o ,a0e diabetesO during t,is .eriod o* +ajor li*e transitions, 3out, begin to +o0e out o* t,eir .arents< ,o+e and +ust beco+e +ore *ull3 res.onsible *or t,eir diabetes care including t,e +an3 as.ects o* sel* +anage+ent, +a1ing +ed/ ical a..oint+ents, and 5nancing ,ealt, care once t,e3 are no longer co0ered un/ der t,eir .arents< ,ealt, insurance 7:::,::H9. In addition to la.ses in ,ealt, care, t,is is also a .eriod o* deterioration in gl3ce+ic control, increased occurrence o* acute co+.lications, .s3c,o/social/ e+otional/be,a0ioral issues, and e+ergence o* c,ronic co+.lications 7:::8::F9. T,oug, scienti5c e0idence continues to be li+ited, it is clear t,at earl3 and ongoing attention be gi0en to co+.re/ ,ensi0e and coordinated .lanning *or sea+less transition o* all 3out, *ro+ .ediatric to adult ,ealt, care 7:::,::H9. A co+.re,ensi0e discussion regarding t,e c,allenges *aced during t,is .eriod, including s.eci5c reco++endations, is *ound in t,e ADA .osition state+ent =Di/ abetes Care *or E+erging Adults> Reco+/ +endations *or Transition 6ro+ #ediatric to Adult Diabetes Care S3ste+s? 7::H9. T,e $ational Diabetes Education #ro/ gra+ 7$DE#9 ,as +aterials a0ailable to *acilitate t,e transition .rocess 7,tt.>@@nde. .ni,.go0@transitions@9, and T,e Endocrine Societ3 7in collaboration 4it, t,e ADA and ot,er organi;ations ,as de0elo.ed transition tools *or clinicians and 3out,@

*a+ilies 7 , tt .> @ @ 4 44 . e ndo / so c i e t 3 . o r g @ clinical.ractice@transitionWo*Wcare.c*+9. (. T3.e ( diabetes T,e incidence o* t3.e ( diabetes in ado/ lescents is increasing, es.eciall3 in et,nic +inorit3 .o.ulations 7!%9. Distinction bet4een t3.e % and t3.e ( diabetes in c,ildren can be di*5cult, since t,e .re0a/ lence o* o0er4eig,t in c,ildren continues to rise and since autoantigens and 1etosis +a3 be .resent in a substantial nu+ber o* .atients 4it, *eatures o* t3.e ( diabetes 7including obesit3 and acant,osis nigri/ cans9. Suc, a distinction at t,e ti+e o* diagnosis is critical because treat+ent reg/ i+ens, educational a..roac,es, and die/ tar3 counsel 4ill di**er +ar1edl3 bet4een t,e t4o diagnoses. T3.e ( diabetes ,as a signi5cant in/ cidence o* co+orbidities alread3 .resent at t,e ti+e o* diagnosis 7::E9. It is reco+/ +ended t,at blood .ressure +easure+ent, a *asting li.id .ro5le, +icroalbu+inuria as/ sess+ent, and dilated e3e e2a+ination be .er*or+ed at t,e ti+e o* diagnosis. T,ere/ a*ter, screening guidelines and treat+ent reco++endations *or ,3.ertension, d3sli/ .ide+ia, +icroalbu+inuria, and retino.a/ t,3 in 3out, 4it, t3.e ( diabetes are si+ilar to t,ose *or 3out, 4it, t3.e % diabetes. Ad/ ditional .roble+s t,at +a3 need to be ad/ dressed include .ol3c3stic o0arian disease and t,e 0arious co+orbidities associated 4it, .ediatric obesit3 suc, as slee. a.nea, ,e.atic steatosis, ort,o.edic co+.lica/ tions, and .s3c,osocial concerns. T,e ADA consensus state+ent on t,is subject 7!!9 .ro0ides guidance on t,e .re0ention, screening, and treat+ent o* t3.e ( diabetes and its co+orbidities in 3oung .eo.le. !. onogenic diabetes s3ndro+es onogenic *or+s o* diabetes 7neonatal diabetes or +aturit3/onset diabetes o* t,e 3oung9 re.resent a s+all *raction o* c,il/ dren 4it, diabetes 7,HI9, but t,e read3 a0ailabilit3 o* co++ercial genetic testing is no4 enabling a true genetic diagnosis 4it, increasing *re-uenc3. It is i+.ortant to correctl3 diagnose one o* t,e +ono/ genic *or+s o* diabetes, as t,ese c,ildren +a3 be incorrectl3 diagnosed 4it, t3.e % or t3.e ( diabetes, leading to nono.ti+al treat+ent regi+ens and dela3s in diag/ nosing ot,er *a+il3 +e+bers. T,e diagnosis o* +onogenic diabetes s,ould be considered in t,e *ollo4ing settings> diabetes diagnosed 4it,in t,e 5rst " +ont,s o* li*eO in c,ildren 4it, strong *a+il3 ,istor3 o* diabetes but

4it,/ out t3.ical *eatures o* t3.e ( diabetes

7nonobese, lo4/ris1 et,nic grou.9O in c,il/ dren 4it, +ild *asting ,3.ergl3ce+ia 7%))8 %H) +g@dL LH.H8E.H ++olM9, es.eciall3 i* 3oung and nonobeseO and in c,ildren 4it, diabetes but 4it, negati0e autoantibodies 4it,out signs o* obesit3 or insulin resis/ tance. A recent international consensus docu+ent discusses in *urt,er detail t,e di/ agnosis and +anage+ent o* c,ildren 4it, +onogenic *or+s o* diabetes 7::B9. B. #reconce.tion care Reco++endations c A%C le0els s,ould be as close to nor+al as .ossible 7,FI9 in an indi0idual .a/ tient be*ore conce.tion is atte+.ted. 7B9 c Starting at .ubert3, .reconce.tion counseling s,ould be incor.orated in t,e routine diabetes clinic 0isit *or all 4o+en o* c,ildbearing .otential. 7C9 c Ko+en 4it, diabetes 4,o are con/ te+.lating .regnanc3 s,ould be e0al/ uated and, i* indicated, treated *or diabetic retino.at,3, ne.,ro.at,3, neuro.at,3, and CVD. 7B9 c edications used b3 suc, 4o+en s,ould be e0aluated .rior to conce.tion, since drugs co++onl3 used to treat di/ abetes and its co+.lications +a3 be contraindicated or not reco++ended in .regnanc3, including statins, ACE in/ ,ibitors, ARBs, and +ost noninsulin t,era.ies. 7E9 c Since +an3 .regnancies are un.lanned, consider t,e .otential ris1s and bene5ts o* +edications t,at are contraindicated in .regnanc3 in all 4o+en o* c,ild/ bearing .otential and counsel 4o+en using suc, +edications accordingl3. 7E9 ajor congenital +al*or+ations re/ +ain t,e leading cause o* +ortalit3 and serious +orbidit3 in in*ants o* +ot,ers 4it, t3.e % and t3.e ( diabetes. Obser/ 0ational studies indicate t,at t,e ris1 o* +al*or+ations increases continuousl3 4it, increasing +aternal gl3ce+ia during t,e 5rst "8E 4ee1s o* gestation, as de5ned b3 5rst/tri+ester A%C concentrations. T,ere is no t,res,old *or A%C 0alues be/ lo4 4,ic, ris1 disa..ears entirel3. Do4/ e0er, +al*or+ation rates abo0e t,e %8(I bac1ground rate o* nondiabetic .regnan/ cies a..ear to be li+ited to .regnancies in 4,ic, 5rst/tri+ester A%C

concentrations are .%I abo0e t,e nor+al range *or a nondiabetic .regnant 4o+an. #reconce.tion care o* diabetes a./ .ears to reduce t,e ris1 o* congenital +al*or+ations. 6i0e nonrando+i;ed studies co+.ared rates o* +ajor +al*or/ +ations in in*ants bet4een 4o+en 4,o

.artici.ated in .reconce.tion diabetes care .rogra+s and 4o+en 4,o initiated intensi0e diabetes +anage+ent a*ter t,e3 4ere alread3 .regnant. T,e .reconce./ tion care .rogra+s 4ere +ultidisci.linar3 and designed to train .atients in diabetes sel*/+anage+ent 4it, diet, intensi5ed insulin t,era.3, and S BC. Coals 4ere set to ac,ie0e nor+al blood glucose con/ centrations, and .E)I o* subjects ac,/ ie0ed nor+al A%C concentrations be*ore t,e3 beca+e .regnant. In all 50e studies, t,e incidence o* +ajor congenital +al*or/ +ations in 4o+en 4,o .artici.ated in .reconce.tion care 7range %.)8%.FI o* in*ants9 4as +uc, lo4er t,an t,e inci/ dence in 4o+en 4,o did not .artici.ate 7range %.:8%).BI o* in*ants9 7%)"9. One li+itation o* t,ese studies is t,at .artici/ .ation in .reconce.tion care 4as sel*/ selected rat,er t,an rando+i;ed. T,us, it is i+.ossible to be certain t,at t,e lo4er +al*or+ation rates resulted *ull3 *ro+ i+.ro0ed diabetes care. $onet,eless, t,e e0idence su..orts t,e conce.t t,at +al*or+ations can be reduced or .re0en/ ted b3 care*ul +anage+ent o* diabetes be/ *ore .regnanc3. #lanned .regnancies greatl3 *acilitate .reconce.tion diabetes care. Un*ortu/ natel3, nearl3 t4o/t,irds o* .regnancies in 4o+en 4it, diabetes are un.lanned, leading to a .ersistent e2cess o* +al*or/ +ations in in*ants o* diabetic +ot,ers. To +ini+i;e t,e occurrence o* t,ese de0as/ tating +al*or+ations, standard care *or all 4o+en 4it, diabetes 4,o ,a0e c,ild/ bearing .otential, beginning at t,e onset o* .ubert3 or at diagnosis, s,ould include %9 education about t,e ris1 o* +al*or+a/ tions associated 4it, un.lanned .regnan/ cies and .oor +etabolic control and (9 use o* e**ecti0e contrace.tion at all ti+es, unless t,e .atient ,as good +etabolic control and is acti0el3 tr3ing to concei0e. Ko+en conte+.lating .regnanc3 need to be seen *re-uentl3 b3 a +ultidis/ ci.linar3 tea+ e2.erienced in t,e +an/ age+ent o* diabetes be*ore and during .regnanc3. T,e goals o* .reconce.tion care are to %9 in0ol0e and e+.o4er t,e .atient in t,e +anage+ent o* ,er diabe/ tes, (9 ac,ie0e t,e lo4est A%C test results .ossible 4it,out e2cessi0e ,3.ogl3ce+ia, !9 assure e**ecti0e contrace.tion until sta/ ble and acce.table gl3ce+ia is ac,ie0ed, and :9 identi*3, e0aluate, and treat long/ ter+ diabetes co+.lications suc, as retino.at,3, ne.,ro.at,3, neuro.at,3, ,3.ertension, and CDD 7%)"9. A+ong t,e drugs co++onl3 used in t,e treat+ent o* .atients 4it, diabetes, a

nu+ber +a3 be relati0el3 or absolutel3 contraindicated during .regnanc3. Sta/ tins are categor3 U 7contraindicated *or use in .regnanc39 and s,ould be discon/ tinued be*ore conce.tion, as s,ould ACE in,ibitors 7:H)9. ARBs are categor3 C 7ris1 cannot be ruled out9 in t,e 5rst tri/ +ester but categor3 D 7.ositi0e e0idence o* ris19 in later .regnanc3 and s,ould generall3 be discontinued be*ore .reg/ nanc3. Since +an3 .regnancies are un/ .lanned, ,ealt, care .ro*essionals caring *or an3 4o+an o* c,ildbearing .otential s,ould consider t,e .otential ris1s and bene5ts o* +edications t,at are contrain/ dicated in .regnanc3. Ko+en using +ed/ ications suc, as statins or ACE in,ibitors need ongoing *a+il3 .lanning counsel/ ing. A+ong t,e oral antidiabetic agents, +et*or+in and acarbose are classi5ed as categor3 B 7no e0idence o* ris1 in ,u/ +ans9 and all ot,ers as categor3 C. #oten/ tial ris1s and bene5ts o* oral antidiabetic agents in t,e .reconce.tion .eriod +ust be care*ull3 4eig,ed, recogni;ing t,at data are insu*5cient to establis, t,e sa*et3 o* t,ese agents in .regnanc3. 6or *urt,er discussion o* .reconce./ tion care, see t,e ADA<s consensus state/ +ent on .re/e2isting diabetes and .regnanc3 7%)"9 and t,e .osition state/ +ent 7:H%9 on t,is subject. C. Older adults Reco++endations c Older adults 4,o are *unctional, cog/ niti0el3 intact, and ,a0e signi5cant li*e e2.ectanc3 s,ould recei0e diabetes care 4it, goals si+ilar to t,ose de/ 0elo.ed *or 3ounger adults. 7E9 c Cl3ce+ic goals *or so+e older adults +ig,t reasonabl3 be rela2ed, using in/ di0idual criteria, but ,3.ergl3ce+ia leading to s3+.to+s or ris1 o* acute ,3.ergl3ce+ic co+.lications s,ould be a0oided in all .atients. 7E9 c Ot,er cardio0ascular ris1 *actors s,ould be treated in older adults 4it, consideration o* t,e ti+e *ra+e o* bene5t and t,e indi0idual .atient. Treat+ent o* ,3.ertension is indicated in 0irtuall3 all older adults, and li.id and as.irin t,era.3 +a3 bene5t t,ose 4it, li*e e2.ectanc3 at least e-ual to t,e ti+e *ra+e o* .ri+ar3 or secondar3 .re0ention trials. 7E9 c Screening *or diabetes co+.lications s,ould be indi0iduali;ed in older adults, but .articular attention s,ould be .aid to co+.lications t,at 4ould lead to *unctional i+.air+ent. 7E9

Diabetes is an i+.ortant ,ealt, condi/ tion *or t,e aging .o.ulationO at least ()I o* .atients o0er t,e age o* "H 3ears ,a0e diabetes, and t,is nu+ber can be e2.ected to gro4 ra.idl3 in t,e co+ing decades. Older indi0iduals 4it, diabetes ,a0e ,ig,er rates o* .re+ature deat,, *unctional disabilit3, and coe2isting illnesses suc, as ,3.ertension, CDD, and stro1e t,an t,ose 4it,out diabetes. Older adults 4it, diabe/ tes are also at greater ris1 t,an ot,er older adults *or se0eral co++on geriatric s3n/ dro+es, suc, as .ol3.,ar+ac3, de.res/ sion, cogniti0e i+.air+ent, urinar3 incontinence, injurious *alls, and .ersistent .ain. A consensus re.ort on diabetes and older adults 7:H(9 inAuenced t,e *ollo4/ ing discussion and reco++endations. T,e care o* older adults 4it, diabetes is co+.licated b3 t,eir clinical and *unc/ tional ,eterogeneit3. So+e older indi0id/ uals de0elo.ed diabetes 3ears earlier and +a3 ,a0e signi5cant co+.licationsO ot,/ ers 4,o are ne4l3 diagnosed +a3 ,a0e ,ad 3ears o* undiagnosed diabetes 4it, resultant co+.lications or +a3 ,a0e trul3 recent/onset disease and *e4 or no co+/ .lications. So+e older adults 4it, diabe/ tes are *rail and ,a0e ot,er underl3ing c,ronic conditions, substantial diabetes/ related co+orbidit3, or li+ited .,3sical or cogniti0e *unctioning. Ot,er older in/ di0iduals 4it, diabetes ,a0e little co+or/ bidit3 and are acti0e. Li*e e2.ectancies are ,ig,l3 0ariable *or t,is .o.ulation, but o*ten longer t,an clinicians reali;e. #ro/ 0iders caring *or older adults 4it, diabe/ tes +ust ta1e t,is ,eterogeneit3 into consideration 4,en setting and .rioriti;/ ing treat+ent goals. T,ere are *e4 long/ter+ studies in older adults de+onstrating t,e bene5ts o* intensi0e gl3ce+ic, blood .ressure, and li.id control. #atients 4,o can be e2.ected to li0e long enoug, to rea. t,e bene5ts o* long/ter+ intensi0e diabetes +anage+ent, 4,o ,a0e good cogniti0e and *unctional *unction, and 4,o c,oose to do so 0ia s,ared decision +a1ing +a3 be treated using t,era.eutic inter0entions and goals si+ilar to t,ose *or 3ounger adults 4it, diabetes. As 4it, all .atients, DS E and ongoing DS S are 0ital co+/ .onents o* diabetes care *or older adults and t,eir caregi0ers. 6or .atients 4it, ad0anced diabetes co+.lications, li*e/li+iting co+orbid ill/ ness, or substantial cogniti0e or *unc/ tional i+.air+ent, it is reasonable to set

less intensi0e gl3ce+ic target goals. T,ese .atients are less li1el3 to bene5t *ro+

reducing t,e ris1 o* +icro0ascular co+/ .lications and +ore li1el3 to su**er seri/ ous ad0erse e**ects *ro+ ,3.ogl3ce+ia. Do4e0er, .atients 4it, .oorl3 controlled diabetes +a3 be subject to acute co+.li/ cations o* diabetes, including de,3dration, .oor 4ound ,ealing, and ,3.ergl3ce+ic ,3.eros+olar co+a. Cl3ce+ic goals at a +ini+u+ s,ould a0oid t,ese conse/ -uences. Alt,oug, control o* ,3.ergl3ce+ia +a3 be i+.ortant in older indi0iduals 4it, diabetes, greater reductions in +or/ bidit3 and +ortalit3 +a3 result *ro+ control o* ot,er cardio0ascular ris1 *ac/ tors rat,er t,an *ro+ tig,t gl3ce+ic con/ trol alone. T,ere is strong e0idence *ro+ clinical trials o* t,e 0alue o* treating ,3.ertension in t,e elderl3 7:H!,:H:9. T,ere is less e0idence *or li.id/lo4ering and as.irin t,era.3, alt,oug, t,e bene5ts o* t,ese inter0entions *or .ri+ar3 and secondar3 .re0ention are li1el3 to a..l3 to older adults 4,ose li*e e2.ectancies e-ual or e2ceed t,e ti+e *ra+es seen in clinical trials. S.ecial care is re-uired in .rescribing and +onitoring .,ar+acological t,era.3 in older adults. Costs +a3 be a signi5cant *actor, es.eciall3 since older adults tend to be on +an3 +edications. et*or+in +a3 be contraindicated because o* renal insu*5cienc3 or signi5cant ,eart *ailure. T,ia;olidinediones, i* used at all, s,ould be used 0er3 cautiousl3 in t,ose 4it,, or at ris1 *or, CD6 and ,a0e also been associated 4it, *ractures. Sul*on3lureas, ot,er insulin secretagogues, and insulin can cause ,3.ogl3ce+ia. Insulin use re/ -uires t,at .atients or caregi0ers ,a0e good 0isual and +otor s1ills and cogniti0e abil/ it3. Di.e.tid3l .e.tidase : 7D##/:9 in,ib/ itors ,a0e *e4 side e**ects, but t,eir costs +a3 be a barrier to so+e older .atientsO t,e latter is also t,e case *or CL#/% agonists. Screening *or diabetes co+.lications in older adults also s,ould be indi0idual/ i;ed. #articular attention s,ould be .aid to co+.lications t,at can de0elo. o0er s,ort .eriods o* ti+e and@or t,at 4ould signi5cantl3 i+.air *unctional status, suc, as 0isual and lo4er/e2tre+it3 co+/ .lications. D. C3stic 5brosis8related diabetes Reco++endations c Annual screening *or c3stic 5brosis8 related diabetes 7C6RD9 4it, OCTT s,ould begin b3 age %) 3ears in all .a/ tients 4it, c3stic 5brosis 4,o do not ,a0e C6RD 7B9. Use o* A%C as a

screening test *or C6RD is not reco+/ +ended. 7B9 During a .eriod o* stable ,ealt,, t,e diagnosis o* C6RD can be +ade in c3stic 5brosis .atients according to usual glucose criteria. 7E9 #atients 4it, C6RD s,ould be treated 4it, insulin to attain indi0iduali;ed gl3ce+ic goals. 7A9 Annual +onitoring *or co+.lications o* diabetes is reco++ended, beginning H 3ears a*ter t,e diagnosis o* C6RD. 7E9

%:) +g@dL 7".%8F.E ++ol@L9 +a3 be

C6RD is t,e +ost co++on co+orbidit3 in .ersons 4it, c3stic 5brosis, occurring in about ()I o* adolescents and :)8H)I o* adults. T,e additional diagnosis o* di/ abetes in t,is .o.ulation is associated 4it, 4orse nutritional status, +ore se0ere inAa++ator3 lung disease, and greater +ortalit3 *ro+ res.irator3 *ailure. Insulin insu*5cienc3 related to .artial 5brotic de/ struction o* t,e islet +ass is t,e .ri+ar3 de*ect in C6RD. Ceneticall3 deter+ined *unction o* t,e re+aining b/ cells and in/ sulin resistance associated 4it, in*ection and inAa++ation +a3 also .la3 a role. Encouraging ne4 data suggest t,at earl3 detection and aggressi0e insulin t,era.3 ,a0e narro4ed t,e ga. in +ortalit3 be/ t4een c3stic 5brosis .atients 4it, and 4it,out diabetes and ,a0e eli+inated t,e se2 di**erence in +ortalit3 7:HH9. Reco++endations *or t,e clinical +anage+ent o* C6RD can be *ound in t,e recent ADA .osition state+ent on t,is to.ic 7:H"9. IU. DIABETES CARE I$ S#ECI6IC SETTI$CS A. Diabetes care in t,e ,os.ital Reco++endations c All .atients 4it, diabetes ad+itted to t,e ,os.ital s,ould ,a0e t,eir diabetes clearl3 identi5ed in t,e +edical record. 7E9 c All .atients 4it, diabetes s,ould ,a0e an order *or blood glucose +onitoring, 4it, results a0ailable to all +e+bers o* t,e ,ealt, care tea+. 7E9 c Coals *or blood glucose le0els> c Criticall3 ill .atients> Insulin t,er/ a.3 s,ould be initiated *or treat+ent o* .ersistent ,3.ergl3ce+ia starting at a t,res,old o* no greater t,an %E) +g@dL 7%) ++ol@L9. Once insulin t,era.3 is started, a glucose range o* %:)8%E) +g@dL 7F.E8%) ++ol@L9 is reco++ended *or t,e +ajorit3 o* criticall3 ill .atients. 7A9 c ore stringent goals, suc, as %%)8

a..ro.riate *or selected .atients, as long as t,is can be ac,ie0ed 4it,out signi5cant ,3.ogl3ce+ia. 7C9 c Criticall3 ill .atients re-uire an intra0e/ nous insulin .rotocol t,at ,as de+on/ strated e*5cac3 and sa*et3 in ac,ie0ing t,e desired glucose range 4it,out in/ creasing ris1 *or se0ere ,3.ogl3ce+ia. 7E9 c $on8criticall3 ill .atients> T,ere is no clear e0idence *or s.eci5c blood glucose goals. I* treated 4it, insulin, t,e .re/ +eal blood glucose targets generall3 ,%:) +g@dL 7F.E ++ol@L9 4it, ran/ do+ blood glucose ,%E) +g@dL 7%).) ++ol@L9 are reasonable, .ro0ided t,ese targets can be sa*el3 ac,ie0ed. ore stringent targets +a3 be a..ro/ .riate in stable .atients 4it, .re0ious tig,t gl3ce+ic control. Less stringent targets +a3 be a..ro.riate in t,ose 4it, se0ere co+orbidities. 7E9 Sc,eduled subcutaneous insulin 4it, basal, nutritional, and correction co+/ .onents is t,e .re*erred +et,od *or ac,ie0ing and +aintaining glucose con/ trol in non8criticall3 ill .atients. 7C9 Clucose +onitoring s,ould be initiated in an3 .atient not 1no4n to be diabetic 4,o recei0es t,era.3 associated 4it, ,ig, ris1 *or ,3.ergl3ce+ia, including ,ig,/dose glucocorticoid t,era.3, initi/ ation o* enteral or .arenteral nutrition, or ot,er +edications suc, as octreotide or i++unosu..ressi0e +edications. 7B9 I* ,3.ergl3ce+ia is docu+ented and .ersistent, consider treating suc, .a/ tients to t,e sa+e gl3ce+ic goals as .a/ tients 4it, 1no4n diabetes. 7E9 A ,3.ogl3ce+ia +anage+ent .rotocol s,ould be ado.ted and i+.le+ented b3 eac, ,os.ital or ,os.ital s3ste+. A .lan *or .re0enting and treating ,3.o/ gl3ce+ia s,ould be establis,ed *or eac, .atient. E.isodes o* ,3.ogl3ce+ia in t,e ,os.ital s,ould be docu+ented in t,e +edial record and trac1ed. 7E9 Consider obtaining an A%C on .atients 4it, diabetes ad+itted to t,e ,os.ital i* t,e result o* testing in t,e .re0ious (8! +ont,s is not a0ailable. 7E9

Consider obtaining an A%C in .atients 4it, ris1 *actors *or undiagnosed di/ abetes 4,o e2,ibit ,3.ergl3ce+ia in t,e ,os.ital. 7E9 #atients 4it, ,3.ergl3ce+ia in t,e ,os.ital 4,o do not ,a0e a .rior di/ agnosis o* diabetes s,ould ,a0e a./ .ro.riate .lans *or *ollo4/u. testing and care docu+ented at disc,arge. 7E9
c

D3.ergl3ce+ia in t,e ,os.ital can re/ .resent .re0iousl3 1no4n diabetes,

.re0iousl3 undiagnosed diabetes, or ,os/ .ital/related ,3.ergl3ce+ia 7*asting blood glucose J%(" +g@dL or rando+ blood glucose J()) +g@dL occurring during t,e ,os.itali;ation t,at re0erts to nor+al a*ter ,os.ital disc,arge9. T,e di*/ 5cult3 distinguis,ing bet4een t,e second and t,ird categories during t,e ,os.itali/ ;ation +a3 be o0erco+e b3 +easuring an A%C in undiagnosed .atients 4it, ,3.er/ gl3ce+ia, as long as conditions inter*ering 4it, A%C utilit3 7,e+ol3sis, blood trans/ *usion9 ,a0e not occurred. T,e +anage/ +ent o* ,3.ergl3ce+ia in t,e ,os.ital ,as o*ten been considered secondar3 in i+/ .ortance to t,e condition t,at .ro+.ted ad+ission 7:HF9. Do4e0er, a bod3 o* lit/ erature no4 su..orts targeted glucose control in t,e ,os.ital setting *or .oten/ tial i+.ro0ed clinical outco+es. D3.er/ gl3ce+ia in t,e ,os.ital +a3 result *ro+ stress, deco+.ensation o* t3.e % or t3.e ( or ot,er *or+s o* diabetes, and@or +a3 be iatrogenic due to 4it,,olding o* anti,3/ .ergl3ce+ic +edications or ad+inistra/ tion o* ,3.ergl3ce+ia/.ro0o1ing agents suc, as glucocorticoids or 0aso.ressors. T,ere is substantial obser0ational e0/ idence lin1ing ,3.ergl3ce+ia in ,os.ital/ i;ed .atients 74it, or 4it,out diabetes9 to .oor outco+es. Co,ort studies as 4ell as a *e4 earl3 RCTs suggested t,at in/ tensi0e treat+ent o* ,3.ergl3ce+ia i+/ .ro0ed ,os.ital outco+es 7:HF8:HB9. In general, t,ese studies 4ere ,eterogeneous in ter+s o* .atient .o.ulation, blood glu/ cose targets and insulin .rotocols used, .ro0ision o* nutritional su..ort, and t,e .ro.ortion o* .atients recei0ing insulin, 4,ic, li+its t,e abilit3 to +a1e +eaning/ *ul co+.arisons a+ong t,e+. Recent tri/ als in criticall3 ill .atients ,a0e *ailed to s,o4 a signi5cant i+.ro0e+ent in +or/ talit3 4it, intensi0e gl3ce+ic control 7:"),:"%9 or ,a0e e0en s,o4n increased +ortalit3 ris1 7:"(9. oreo0er, t,ese re/ cent RCTs ,a0e ,ig,lig,ted t,e ris1 o* se0ere ,3.ogl3ce+ia resulting *ro+ suc, e**orts 7:")8:"H9. T,e largest stud3 to date, $ICE/ SUCAR 7$or+ogl3cae+ia in Intensi0e Care E0aluation and Sur0i0al Using Clu/ cose Algorit,+ Regulation9, a +ulticen/ ter, +ultinational RCT, co+.ared t,e e**ect o* intensi0e gl3ce+ic control 7target E%8%)E +g@dL, +ean blood glucose at/ tained %%H +g@dL9 to standard gl3ce+ic control 7target %::8%E) +g@dL, +ean blood glucose attained %:: +g@dL9 on outco+es a+ong ",%): criticall3 ill .ar/ tici.ants, al+ost all o* 4,o+ re-uired +e/ c,anical 0entilation 7:"(9. $inet3/da3

+ortalit3 4as signi5cantl3 ,ig,er in t,e intensi0e 0ersus t,e con0entional grou. in bot, surgical and +edical .a/ tients, as 4as +ortalit3 *ro+ cardio0ascu/ lar causes. Se0ere ,3.ogl3ce+ia 4as also +ore co++on in t,e intensi0el3 treated grou. 7".EI 0s. ).HI, # , ).))%9. T,e .recise reason *or t,e increased +ortalit3 in t,e tig,tl3 controlled grou. is un/ 1no4n. T,e results o* t,is stud3 lie in star1 contrast to a *a+ous ())% single/ center stud3 t,at re.orted a :(I relati0e reduction in intensi0e care unit 7ICU9 +ortalit3 in criticall3 ill surgical .atients treated to a target blood glucose o* E)8%%) +g@dL 7:HE9. I+.ortantl3, t,e control grou. in $ICE/SUCAR ,ad reasonabl3 good blood glucose +anage+ent, +ain/ tained at a +ean glucose o* %:: +g@dL, onl3 (B +g@dL abo0e t,e intensi0el3 +an/ aged .atients. Accordingl3, t,is stud3<s 5ndings do not dis.ro0e t,e notion t,at gl3ce+ic control in t,e ICU is i+.ortant. Do4e0er, t,e3 do strongl3 suggest t,at it +a3 not be necessar3 to target blood glu/ cose 0alues ,%:) +g@dL and t,at a ,ig,l3 stringent target o* ,%%) +g@dL +a3 actu/ all3 be dangerous. In a recent +eta/anal3sis o* (" trials 7$ H %!,H"F9, 4,ic, included t,e $ICE/ SUCAR data, t,e .ooled RR o* deat, 4it, intensi0e insulin t,era.3 4as ).B! as co+.ared 4it, con0entional t,era.3 7BHI CI ).E!8 %.):9 7:"H9. A..ro2i/ +atel3 ,al* o* t,ese trials re.orted ,3.o/ gl3ce+ia, 4it, a .ooled RR o* intensi0e t,era.3 o* ".) 7BHI CI :.H8E.)9. T,e s.eci5c ICU setting inAuenced t,e 5nd/ ings, 4it, .atients in surgical ICUs a./ .earing to bene5t *ro+ intensi0e insulin t,era.3 7RR )."!, BHI CI ).::8).B%9, 4,ereas t,ose in ot,er +edical and +i2ed critical care settings did not. It 4as concluded t,at, o0erall, intensi0e in/ sulin t,era.3 increased t,e ris1 o* ,3.o/ gl3ce+ia but .ro0ided no o0erall bene5t on +ortalit3 in t,e criticall3 ill, alt,oug, a .ossible +ortalit3 bene5t to .atients ad+itted to t,e surgical ICU 4as suggested. %. Cl3ce+ic targets in ,os.itali;ed .atients De5nition o* glucose abnor+alities in t,e ,os.ital setting D3.ergl3ce+ia in t,e ,os.ital ,as been de5ned as an3 blood glucose .%:) +g@dL 7F.E ++ol@L9. Le0els t,at are signi5cantl3 and .ersistentl3 abo0e t,is +a3 re-uire treat+ent in ,os.itali;ed .atients. A%C 0alues .".HI suggest, in undiagnosed

.atients, t,at diabetes .receded ,os.itali/ ;ation 7:""9. D3.ogl3ce+ia ,as been de/ 5ned as an3 blood glucose ,F) +g@dL 7!.B ++ol@L9. T,is is t,e standard de5ni/ tion in out.atients and correlates 4it, t,e initial t,res,old *or t,e release o* counter/ regulator3 ,or+ones. Se0ere ,3.ogl3ce/ +ia in ,os.itali;ed .atients ,as been de/ 5ned b3 +an3 as ,:) +g@dL 7(.( ++ol@L9, alt,oug, t,is is lo4er t,an t,e OH) +g@dL 7(.E ++ol@L9 le0el at 4,ic, cogniti0e i+/ .air+ent begins in nor+al indi0iduals 7:"F9. As 4it, ,3.ergl3ce+ia, ,3.ogl3ce/ +ia a+ong in.atients is also associated 4it, ad0erse s,ort/ and long/ter+ out/ co+es. Earl3 recognition and treat+ent o* +ild to +oderate ,3.ogl3ce+ia 7:)8 "B +g@dL L(.(8!.E ++ol@LM9 can .re0ent deterioration to a +ore se0ere e.isode 4it, .otential ad0erse se-uelae 7:"E9. Criticall3 ill .atients Based on t,e 4eig,t o* t,e a0ailable e0idence, *or t,e +ajorit3 o* criticall3 ill .atients in t,e ICU setting, insulin in*usion s,ould be used to control ,3.ergl3ce+ia, 4it, a starting t,res,old o* no ,ig,er t,an %E) +g@dL 7%).) ++ol@L9. Once intra0e/ nous insulin is started, t,e glucose le0el s,ould be +aintained bet4een %:) and %E) +g@dL 7F.E and %).) ++ol@L9. Creater bene5t +a3be reali;ed at t,e lo4er end o* t,is range. Alt,oug, strong e0idence is lac1ing, so+e4,at lo4er glucose targets +a3 be a..ro.riate in selected .atients. One s+all stud3 suggested t,at +edical intensi0e care unit 7 ICU9 .atients treated to targets o* %()8%:) +g@dL ,ad less neg/ ati0e nitrogen balance t,an t,ose treated to ,ig,er targets 7:"B9. Do4e0er, targets ,%%) +g@dL 7".% ++ol@L9 are not reco+/ +ended. Use o* insulin in*usion .rotocols 4it, de+onstrated sa*et3 and e*5cac3, re/ sulting in lo4 rates o* ,3.ogl3ce+ia, are ,ig,l3 reco++ended 7:"E9. $on8criticall3 ill .atients Kit, no .ros.ecti0e RCT data to in*or+ s.eci5c gl3ce+ic targets in non8 criticall3 ill .atients, reco++endations are based on clinical e2.erience and judg+ent 7:F)9. 6or t,e +ajorit3 o* non8criticall3 ill .atients treated 4it, insulin, .re+eal glucose targets s,ould

generall3 be ,%:) +g@dL 7F.E ++ol@L9 4it, rando+ blood glucose ,%E) +g@dL 7%).) ++ol@L9, as long as t,ese targets can be sa*el3 ac,ie0ed. To a0oid ,3.ogl3ce+ia, consideration s,ould be gi0en to reassessing t,e insulin regi+en i* blood glucose le0els *all belo4 %)) +g@dL 7H." ++ol@L9. odi5cation o* t,e regi+en is re-uired 4,en blood

glucose 0alues are ,F) +g@dL 7!.B ++ol@L9, unless t,e e0ent is easil3 e2/ .lained b3 ot,er *actors 7suc, as a +issed +eal9. T,ere is so+e e0idence t,at s3ste+/ atic attention to ,3.ergl3ce+ia in t,e e+ergenc3 roo+ leads to better gl3ce+ic control in t,e ,os.ital *or t,ose subse/ -uentl3 ad+itted 7:F%9. Occasional .atients 4it, a .rior ,is/ tor3 o* success*ul tig,t gl3ce+ic control in t,e out.atient setting 4,o are clinicall3 stable +a3 be +aintained 4it, a glucose range belo4 t,e abo0e cut .oints. Con/ 0ersel3, ,ig,er glucose ranges +a3 be acce.table in ter+inall3 ill .atients or in .atients 4it, se0ere co+orbidities, as 4ell as in t,ose in .atient care settings 4,ere *re-uent glucose +onitoring or close nursing su.er0ision is not *easible. Clinical judg+ent, co+bined 4it, ongoing assess+ent o* t,e .atient<s clini/ cal status, including c,anges in t,e trajec/ tor3 o* glucose +easures, t,e se0erit3 o* illness, nutritional status, or concurrent use o* +edications t,at +ig,t a**ect glu/ cose le0els 7e.g., steroids, octreotide9, +ust be incor.orated into t,e da3/to/ da3 decisions regarding insulin dosing 7:"E9. (. Anti,3.ergl3ce+ic agents in ,os.itali;ed .atients In t,e ,os.ital setting, insulin t,era.3 is t,e .re*erred +et,od o* gl3ce+ic control in +ajorit3 o* clinical situations 7:"E9. In t,e ICU, intra0enous in*usion is t,e .re/ *erred route o* insulin ad+inistration. K,en t,e .atient is transitioned o** intra/ 0enous insulin to subcutaneous t,era.3, .recautions s,ould be ta1en to .re0ent ,3.ergl3ce+ia esca.e 7:F(,:F!9. Outside o* critical care units, sc,eduled subcuta/ neous insulin t,at deli0ers basal, nutri/ tional, and correction 7su..le+ental9 co+.onents is .re*erred. T3.ical dosing sc,e+es are based on bod3 4eig,t, 4it, so+e e0idence t,at .atients 4it, renal in/ su*5cienc3 s,ould be treated 4it, lo4er doses 7:F:9. #rolonged t,era.3 4it, sliding/scale insulin 7SSI9 as t,e sole regi+en is ine**ecti0e in t,e +ajorit3 o* .atients, increases ris1 o* bot, ,3.ogl3/ ce+ia and ,3.ergl3ce+ia, and ,as re/ centl3 been s,o4n in a rando+i;ed trial to be associated 4it, ad0erse outco+es in general surger3 .atients 4it, t3.e ( diabe/ tes 7:FH9. SSI is .otentiall3 dangerous in t3.e % diabetes 7:"E9. T,e reader is re*erred to se0eral recent .ublications and re0ie4s t,at describe currentl3 a0ailable insulin .re.arations and .rotocols and .ro0ide guidance in use o* insulin t,era.3 in

s.eci5c clinical settings including .aren/ teral nutrition 7:F"9, enteral tube *eedings and 4it, ,ig, dose glucocorticoid t,era.3 7:"E9. T,ere are no data on t,e sa*et3 and e*5cac3 o* oral agents and injectable non/ insulin t,era.ies suc, as CL#/% analogs and .ra+lintide in t,e ,os.ital. T,e3 are generall3 considered to ,a0e a li+ited role in t,e +anage+ent o* ,3.ergl3ce+ia in conjunction 4it, acute illness. Continu/ ation o* t,ese agents +a3 be a..ro.riate in selected stable .atients 4,o are e2.ected to consu+e +eals at regular inter0als, and t,e3 +a3 be initiated or resu+ed in antici.ation o* disc,arge once t,e .atient is clinicall3 stable. S.eci5c caution is re-uired 4it, +et*or+in, due to t,e .ossibilit3 t,at a contraindication +a3 de0elo. during t,e ,os.itali;ation, suc, as renal insu*5cienc3, unstable ,e/ +od3na+ic status, or need *or an i+aging stud3 t,at re-uires a radio/ contrast d3e. !. #re0enting ,3.ogl3ce+ia In t,e ,os.ital, +ulti.le ris1 *actors *or ,3.ogl3ce+ia are .resent. #atients 4it, or 4it,out diabetes +a3 e2.erience ,3/ .ogl3ce+ia in t,e ,os.ital in association 4it, altered nutritional state, ,eart *ail/ ure, renal or li0er disease, +alignanc3, in*ection, or se.sis. Additional triggering e0ents leading to iatrogenic ,3.ogl3ce+ia include sudden reduction o* corticoste/ roid dose, altered abilit3 o* t,e .atient to re.ort s3+.to+s, reduction o* oral in/ ta1e, e+esis, ne4 $#O status, ina..ro/ .riate ti+ing o* s,ort/ or ra.id/acting insulin in relation to +eals, reduction o* rate o* ad+inistration o* intra0enous de2/ trose, and une2.ected interru.tion o* enteral *eedings or .arenteral nutrition. Des.ite t,e .re0entable nature o* +an3 in.atient e.isodes o* ,3.ogl3ce+ia, insti/ tutions are +ore li1el3 to ,a0e nursing .rotocols *or t,e treat+ent o* ,3.ogl3ce/ +ia t,an *or its .re0ention. Trac1ing suc, e.isodes and anal3;ing t,eir causes are i+.ortant -ualit3/i+.ro0e+ent acti0ities 7:"E9. :. Diabetes care .ro0iders in t,e ,os.ital In.atient diabetes +anage+ent +a3 be e**ecti0el3 c,a+.ioned and@or .ro0ided b3 .ri+ar3 care .,3sicians, endocrinolo/ gists, intensi0ists, or ,os.italists. In0ol0e/ +ent o* a..ro.riatel3 trained s.ecialists

or s.ecialt3 tea+s +a3 reduce lengt, o* sta3, i+.ro0e gl3ce+ic control, and i+/ .ro0e outco+es 7:"E9. In t,e care o* di/ abetes, i+.le+entation o* standardi;ed

order sets *or sc,eduled and correction/ dose insulin +a3 reduce reliance on sliding/scale +anage+ent. As ,os.itals +o0e to co+.l3 4it, =+eaning*ul use? regulations *or electronic ,ealt, records, as +andated b3 t,e Dealt, In*or+ation Tec,nolog3 Act, e**orts s,ould be +ade to assure t,at all co+.onents o* struc/ tured insulin order sets are incor.orated into electronic insulin order sets 7:FF,:FE9. A tea+ a..roac, is needed to estab/ lis, ,os.ital .at,4a3s. To ac,ie0e gl3ce/ +ic targets associated 4it, i+.ro0ed ,os.ital outco+es, ,os.itals 4ill need +ultidisci.linar3 su..ort to de0elo. in/ sulin +anage+ent .rotocols t,at e**ec/ ti0el3 and sa*el3 enable ac,ie0e+ent o* gl3ce+ic targets 7:FB9. H. Sel*/+anage+ent in t,e ,os.ital Sel*/+anage+ent o* diabetes in t,e ,os/ .ital +a3 be a..ro.riate *or co+.etent adult .atients 4,o ,a0e a stable le0el o* consciousness, ,a0e reasonabl3 stable dail3 insulin re-uire+ents, success*ull3 conduct sel*/+anage+ent o* diabetes at ,o+e, ,a0e .,3sical s1ills needed to success*ull3 sel*/ ad+inister insulin and .er*or+ S BC, ,a0e ade-uate oral in/ ta1e, and are .ro5cient in carbo,3drate counting, use o* +ulti.le dail3 insulin injections or insulin .u+. t,era.3, and sic1/da3 +anage+ent. T,e .atient and .,3sician, in consultation 4it, nursing sta**, +ust agree t,at .atient sel*/ +anage+ent is a..ro.riate under t,e conditions o* ,os.itali;ation. #atients 4,o use CSII .u+. t,era.3 in t,e out.atient setting can be candidates *or diabetes sel*/+anage+ent in t,e ,os/ .ital, .ro0ided t,at t,e3 ,a0e t,e +ental and .,3sical ca.acit3 to do so 7:"E9. A ,os.ital .olic3 and .rocedures delineat/ ing in.atient guidelines *or CSII t,era.3 are ad0isable, and a0ailabilit3 o* ,os.ital .ersonnel 4it, e2.ertise in CSII t,era.3 is essential. It is i+.ortant t,at nursing .ersonnel docu+ent basal rates and bolus doses ta1en on a regular basis 7at least dail39. ". $T in t,e ,os.ital T,e goals o* $T are to o.ti+i;e gl3ce/ +ic control, to .ro0ide ade-uate calories to +eet +etabolic de+ands, and to create a disc,arge .lan *or *ollo4/u. care 7:HF,:E)9. T,e ADA does not en/ dorse an3 single +eal .lan or s.eci5ed .ercentages o* +acronutrients, and t,e

ter+ =ADA diet? s,ould no longer be used. Current nutrition reco++enda/ tions ad0ise indi0iduali;ation based on

treat+ent goals, .,3siological .ara+e/ ters, and +edication usage. Consistent carbo,3drate +eal .lans are .re*erred b3 +an3 ,os.itals because t,e3 *acilitate +atc,ing t,e .randial insulin dose to t,e a+ount o* carbo,3drate consu+ed 7:E%9. Because o* t,e co+.le2it3 o* nutrition is/ sues in t,e ,os.ital, a registered dietitian, 1no4ledgeable and s1illed in $T, s,ould ser0e as an in.atient tea+ +e+/ ber. T,e dietitian is res.onsible *or inte/ grating in*or+ation about t,e .atient<s clinical condition, eating, and li*est3le ,abits and *or establis,ing treat+ent goals in order to deter+ine a realistic .lan *or nutrition t,era.3 7:E(,:E!9. F. Bedside blood glucose +onitoring #OC blood glucose +onitoring .er/ *or+ed at t,e bedside is used to guide insulin dosing. In t,e .atient 4,o is recei0ing nutrition, t,e ti+ing o* glucose +onitoring s,ould +atc, carbo,3drate e2.osure. In t,e .atient 4,o is not re/ cei0ing nutrition, glucose +onitoring is .er*or+ed e0er3 : to " , 7:E:,:EH9. ore *re-uent blood glucose testing ranging *ro+ e0er3 !) +in to e0er3 ( , is re-uired *or .atients on intra0enous insulin in*usions. Sa*et3 standards s,ould be estab/ lis,ed *or blood glucose +onitoring .ro/ ,ibiting s,aring o* 5nger/stic1 lancing de0ices, lancets, needles, and +eters to reduce t,e ris1 o* trans+ission o* blood borne diseases. S,ared lancing de0ices carr3 essentiall3 t,e sa+e ris1 as is con*erred *ro+ s,aring o* s3ringes and needles 7:E"9. Accurac3 o* blood glucose +easure/ +ents using #OC +eters ,as li+itations t,at +ust be considered. Alt,oug, t,e 6DA allo4s a %@( ()I error *or blood glucose +eters, -uestions about t,e a./ .ro.riateness o* t,ese criteria ,a0e been raised 7!EE9. Clucose +easures di**er sig/ ni5cantl3 bet4een .las+a and 4,ole blood, ter+s t,at are o*ten used inter/ c,angeabl3 and can lead to +isinter.re/ tation. ost co++erciall3 a0ailable ca.illar3 blood glucose +eters introduce a correction *actor o* O%.%( to re.ort a =.las+a/adjusted? 0alue 7:EF9. Signi5cant discre.ancies bet4een ca.illar3, 0enous, and arterial .las+a sa+.les ,a0e been obser0ed in .atients 4it, lo4 or ,ig, ,e+oglobin concentra/ tions, ,3.o.er*usion, and t,e .resence o* inter*ering substances .articularl3 +altose, as contained in i++unoglobu/ lins 7:EE9. Anal3tical 0ariabilit3 ,as been described 4it, se0eral #OC +eters 7:EB9. Increasingl3 ne4er generation #OC blood glucose +eters correct *or 0ariation in

,e+atocrit and *or inter*ering substances. An3 glucose result t,at does not correlate 4it, t,e .atient<s status s,ould be con/ 5r+ed t,roug, con0entional laborator3 sa+.ling o* .las+a glucose. T,e 6DA ,as beco+e increasingl3 concerned about t,e use o* #OC blood glucose +eters in t,e ,os.ital and is .resentl3 re0ie4ing +atters related to t,eir use. E. Disc,arge .lanning and DS E Transition *ro+ t,e acute care setting is a ,ig,/ris1 ti+e *or all .atients, not just t,ose 4it, diabetes or ne4 ,3.ergl3ce+ia. Al/ t,oug, t,ere is an e2tensi0e literature concerning sa*e transition 4it,in and *ro+ t,e ,os.ital, little o* it is s.eci5c to diabetes 7:B)9. It is i+.ortant to re+e+ber t,at diabetes disc,arge .lanning is not a se.arate entit3, but is .art o* an o0erall dis/ c,arge .lan. As suc,, disc,arge .lanning begins at ad+ission to t,e ,os.ital and is u.dated as .rojected .atient needs c,ange. In.atients +a3 be disc,arged to 0ar/ ied settings, including ,o+e 74it, or 4it,out 0isiting nurse ser0ices9, assisted li0ing, re,abilitation, or s1illed nursing *acilities. T,e latter t4o sites are generall3 sta**ed b3 ,ealt, .ro*essionals, so diabe/ tes disc,arge .lanning 4ill be li+ited to co++unication o* +edication and diet orders. 6or t,e .atient 4,o is disc,arged to assisted li0ing or to ,o+e, t,e o.ti+al .rogra+ 4ill need to consider t,e t3.e and se0erit3 o* diabetes, t,e e**ects o* t,e .atient<s illness on blood glucose le0els, and t,e ca.acities and desires o* t,e .a/ tient. S+oot, transition to out.atient care s,ould be ensured. T,e Agenc3 *or Dealt,/ care Researc, and Pualit3 7ADRP9 reco+/ +ends t,at at a +ini+u+, disc,arge .lans include t,e *ollo4ing> edication reconciliation> T,e .a/ tient<s +edications +ust be cross/ c,ec1ed to ensure t,at no c,ronic +edications 4ere sto..ed and to en/ sure t,e sa*et3 o* ne4 .rescri.tions. c K,ene0er .ossible, .rescri.tions *or ne4 or c,anged +edication s,ould be 5lled and re0ie4ed 4it, t,e .atient and *a+il3 at or be*ore disc,arge. c Structured disc,arge co++unication> In*or+ation on +edication c,anges, .ending tests and studies, and *ollo4/ u. needs +ust be accuratel3 and .ro+.tl3 co++unicated to out.atient .,3sicians. c Disc,arge su++aries s,ould be trans/
c

is

+itted to t,e .ri+ar3 .,3sician as soon as .ossible a*ter disc,arge. A..oint+ent 1ee.ing be,a0ior en,anced tea+ 4,en t,e in.atient

sc,edules out.atient +edical *ollo4/ u. .rior to disc,arge. Ideall3 t,e in/ .atient care .ro0iders or case +anagers@ disc,arge .lanners 4ill sc,edule *ol/ lo4/u. 0isit7s9 4it, t,e a..ro.riate .ro*essionals, including t,e .ri+ar3 care .ro0ider, endocrinologist, and di/ abetes educator 7:B%9. Teac,ing diabetes sel*/+anage+ent to .atients in ,os.itals is a c,allenging tas1. #atients are ill, under increased stress related to t,eir ,os.itali;ation and diagnosis, and in an en0iron+ent not conduci0e to learn/ ing. Ideall3, .eo.le 4it, diabetes s,ould be taug,t at a ti+e and .lace conduci0e to learning> as an out.atient in a recogni;ed .rogra+ o* diabetes education. 6or t,e ,os.itali;ed .atient, diabetes =sur0i0al s1ills? education is generall3 a *easible a./ .roac, to .ro0ide su*5cient in*or+ation and training to enable sa*e care at ,o+e. #atients ,os.itali;ed because o* a crisis re/ lated to diabetes +anage+ent or .oor care at ,o+e need education to .re0ent subse/ -uent e.isodes o* ,os.itali;ation. An as/ sess+ent o* t,e need *or a ,o+e ,ealt, re*erral or re*erral to an out.atient diabetes education .rogra+ s,ould be .art o* dis/ c,arge .lanning *or all .atients. DS E cannot 4ait until disc,arge, es.eciall3 in t,ose ne4 to insulin t,er/ a.3 or in 4,o+ t,e diabetes regi+en ,as been substantiall3 altered during t,e ,os.itali;ation. It is reco++ended t,at t,e *ollo4ing areas o* 1no4ledge be re0ie4ed and addressed .rior to ,os.ital disc,arge>
c

e-ui.+ent, +edication, su..lies, order to a0oid a .otentiall3 dangerous and .rescri.tions at t,e ti+e o* ,iatus in care. T,ese su..lies@.rescri./ disc,arge in tions s,ould include t,e *ollo4ing>
c c c c c c c c

Insulin 70ials or .ens9 i* needed S3ringes or .en needles 7i* needed9 Oral +edications 7i* needed9 Blood glucose +eter and stri.s Lancets and lancing de0ice Urine 1etone stri.s 7t3.e %9 Clucagon e+ergenc3 1it 7insulin/treated9 edical alert a..lication@c,ar+

ore e2.anded diabetes education can be arranged in t,e co++unit3. An out/ .atient *ollo4/u. 0isit 4it, t,e .ri+ar3 care .ro0ider, endocrinologist, or diabetes educator 4it,in % +ont, o* disc,arge is ad0ised *or all .atients ,a0ing ,3.ergl3ce/ +ia in t,e ,os.ital. Clear co++unication 4it, out.atient .ro0iders eit,er directl3 or 0ia ,os.ital disc,arge su++aries *acilitates sa*e transitions to out.atient care. #ro0id/ ing in*or+ation regarding t,e cause or t,e .lan *or deter+ining t,e cause o* ,3.er/ gl3ce+ia, related co+.lications and co/ +orbidities, and reco++ended treat+ents can assist out.atient .ro0iders as t,e3 assu+e ongoing care. B. Diabetes and e+.lo3+ent An3 .erson 4it, diabetes, 4,et,er in/ sulin treated or noninsulin treated, s,ould be eligible *or an3 e+.lo3+ent *or 4,ic, ,e@s,e is ot,er4ise -uali5ed. E+.lo3+ent decisions s,ould ne0er be based on generali;ations or stereot3.es regarding t,e e**ects o* diabetes. K,en -uestions arise about t,e +edical 5tness o* a .erson 4it, diabetes *or a .articular job, a ,ealt, care .ro*essional 4it, e2/ .ertise in treating diabetes s,ould .er/ *or+ an indi0iduali;ed assess+ent. See t,e ADA .osition state+ent on diabetes and e+.lo3+ent 7:B(9. C. Diabetes and dri0ing A large .ercentage o* .eo.le 4it, diabetes in t,e U.S. and else4,ere see1 a license to dri0e, eit,er *or .ersonal or e+.lo3+ent .ur.oses. T,ere ,as been considerable de/ bate 4,et,er, and t,e e2tent to 4,ic,, diabetes +a3 be a rele0ant *actor in de/ ter+ining t,e dri0er abilit3 and eligibilit3 *or a license. #eo.le 4it, diabetes are subject to a great 0ariet3 o* licensing re-uire+ents a./ .lied b3 bot, state and *ederal jurisdic/ tions, 4,ic, +a3 lead to loss o* e+.lo3+ent or signi5cant restrictions on a .erson<s license. #resence o* a +edical condition t,at can lead to signi5cantl3

c c

c c

Identi5cation o* ,ealt, care .ro0ider 4,o 4ill .ro0ide diabetes care a*ter disc,arge Le0el o* understanding related to t,e diagnosis o* diabetes, S BC, and e2/ .lanation o* ,o+e blood glucose goals De5nition, recognition, treat+ent, and .re0ention o* ,3.ergl3ce+ia and ,3/ .ogl3ce+ia In*or+ation on consistent eating .atterns K,en and ,o4 to ta1e blood glucose8 lo4ering +edications including insulin ad+inistration 7i* going ,o+e on in/ sulin9 Sic1/da3 +anage+ent #ro.er use and dis.osal o* needles and s3ringes

It is i+.ortant t,at .atients be .ro/ 0ided 4it, a..ro.riate durable +edical

i+.aired consciousness or cognition +a3 lead to dri0ers being e0aluated *or 5tness to dri0e. 6or diabetes, t,is t3.icall3 arises 4,en t,e .erson ,as ,ad a ,3.ogl3ce+ic e.isode be,ind t,e 4,eel, e0en i* t,is did not lead to a +otor 0e,icle accident. E.ide+iological and si+ulator data suggest t,at .eo.le 4it, insulin/treated diabetes ,a0e a s+all increase in ris1 o* +otor 0e,icle accidents, .ri+aril3 due to ,3.ogl3ce+ia and decreased a4areness o* ,3.ogl3ce+ia. T,is increase 7RR %.%(8 %.%B9 is +uc, s+aller t,an t,e ris1s asso/ ciated 4it, teenage +ale dri0ers 7RR :(9, dri0ing at nig,t 7RR %:(9, dri0ing on rural roads co+.ared 4it, urban roads 7RR B.(9, and obstructi0e slee. a.nea 7RR (.:9, all o* 4,ic, are acce.ted *or unre/ stricted licensure. T,e ADA .osition state+ent on di/ abetes and dri0ing 7:B!9 reco++ends against blan1et restrictions based on t,e diagnosis o* diabetes and urges indi0idual assess+ent b3 a ,ealt, care .ro*essional 1no4ledgeable in diabetes i* restrictions on licensure are being considered. #a/ tients s,ould be e0aluated *or decreased a4areness o* ,3.ogl3ce+ia, ,3.ogl3ce/ +ia e.isodes 4,ile dri0ing, or se0ere ,3/ .ogl3ce+ia. #atients 4it, retino.at,3 or .eri.,eral neuro.at,3 re-uire assess/ +ent to deter+ine i* t,ose co+.lications inter*ere 4it, o.eration o* a +otor 0e,i/ cle. Dealt, care .ro*essionals s,ould be cogni;ant o* t,e .otential ris1 o* dri0ing 4it, diabetes and counsel t,eir .atients about detecting and a0oiding ,3.ogl3ce/ +ia 4,ile dri0ing. D. Diabetes +anage+ent in correctional institutions #eo.le 4it, diabetes in correctional *acil/ ities s,ould recei0e care t,at +eets na/ tional standards. Because it is esti+ated t,at nearl3 E),))) in+ates ,a0e diabetes, correctional institutions s,ould ,a0e 4ritten .olicies and .rocedures *or t,e +anage+ent o* diabetes and *or training o* +edical and correctional sta** in di/ abetes care .ractices. See t,e ADA .osi/ tion state+ent on diabetes +anage+ent in correctional institutions 7:B:9 *or *ur/ t,er discussion. U. STRATECIES 6OR I #ROVI$C DIABETES CARE Reco++endations c Care s,ould be aligned 4it, co+.o/ nents o* t,e C,ronic Care odel 7CC 9 to ensure .roducti0e inter/

actions bet4een a .re.ared .roacti0e

si2 core ele+ents *or t,e .ro0ision o* o./ ti+al care o* .atients 4it, c,ronic dis/ c ease> %9 deli0er3 s3ste+ design 7+o0ing *ro+ a reacti0e to a .roacti0e care deli0er3 s3ste+ 4,ere .lanned 0isits are coordi/ nated t,roug, a tea+ based a..roac,9, (9 sel*/+anage+ent su..ort, !9 decision c su..ort 7basing care on e0idence/ based, e**ecti0e care guidelines9, :9 clinical in*or/ +ation s3ste+s 7using registries t,at can .ro0ide .atient/s.eci5c and .o.ulation/ c based su..ort to t,e care tea+9, H9 co++unit3 resources and .olicies 7iden/ ti*3ing or de0elo.ing resources to su..ort ,ealt,3 li*est3les9, and "9 ,ealt, s3ste+s 7to create a -ualit3/oriented culture9. Re/ de5nition o* t,e roles o* t,e clinic T,ere ,as been stead3 i+.ro0e+ent in sta** and .ro+oting sel*/+anage+ent t,e .ro.ortion o* diabetic .atients on t,e ac,ie0ing reco++ended le0els o* A%C, .art o* t,e .atient are *unda+ental to blood .res/ sure, and LDL c,olesterol in t,e success*ul i+.le+entation o* t,e t,e last %) 3ears, bot, in .ri+ar3 care CC 7H)%9. Collaborati0e, +ultidisci/ settings and in endocrinolog3 .ractices. .linar3 tea+s are best suited to .ro0ide ean A%C na/ tionall3 ,as declined *ro+ suc, care *or .eo.le 4it, c,ronic F.E(I in %BBB8 conditions suc, as diabetes and to *acili/ ())) to F.%EI in ()): based on tate .atients< .er*or+ance o* a..ro.riate $DA$ES data 7:BH9. T,is ,as been sel*/+anage+ent 7%"!,%"H,((),H)(9. acco+.anied b3 i+.ro0e+ents in li.ids $DE# +aintains an online resource and blood .ressure control and led to 7444.betterdiabetescare.ni,.go09 to ,el. substantial reductions in end/stage ,ealt, care .ro*essionals design and i+/ +icro0ascular co+.lications in t,ose .le+ent +ore e**ecti0e ,ealt, care deli0/ 4it, diabetes. $e0ert,eless in so+e er3 s3ste+s *or t,ose 4it, diabetes. studies onl3 HF.%I o* adults 4it, diag/ nosed diabetes ac,ie0ed an A%C o* , T,ree FI, onl3 :H.HI ,ad a blood .ressure , s.eci5c objecti0es, 4it, re*erences to lit/ %!)@E) ++Dg, and just :".HI ,ad a erature t,at outlines .ractical strategies total c,oles/ terol ,()) +g@dL, 4it, to ac,ie0e eac,, are outlined belo4. onl3 %(.(I o* .eo.le 4it, diabetes ac,ie0ing all t,ree treat+ent goals Objecti0e %> O.ti+i;e .ro0ider and 7:B"9. E0idence also sug/ gests t,at tea+ be,a0ior .rogress in ris1 *actor control +a3 be T,e care tea+ s,ould .rioriti;e ti+el3 slo4ing 7:BF9. Certain .atient grou.s, and suc, as .atients 4it, co+.le2 co/ a..ro.riate intensi5cation o* li*est3le +orbidities, 5nancial or ot,er social and@ or .,ar+aceutical t,era.3 o* ,ard/ s,i.s, and@or li+ited Englis, .atients 4,o ,a0e not ac,ie0ed bene5cial .ro5cienc3, +a3 .resent .articular le0els o* blood .ressure, li.id, or glucose c,allenges to goal/ based care 7:BE,:BB9. control 7H)!9. Strategies suc, as #ersistent 0ariation in -ualit3 o* diabetes e2.licit goal setting 4it, .atients care across .ro0iders and across .ractice 7H):9O identi*3ing and ad/ dressing settings e0en a*ter ad/ justing *or .atient language, nu+erac3, or cultural barriers *actors indicates t,at t,ere re+ains to care 7H)H8H)E9O integrating e0i/ dence/ .otential *or substantial *ur/ t,er based guidelines and clinical in*or/ +ation tools into t,e .rocess o* care i+.ro0e+ents in diabetes care. Alt,oug, nu+erous inter0entions to 7H)B8H%%9O and incor.orating care i+.ro0e ad,erence to t,e reco++ended +anage/ +ent tea+s including nurses, standards ,a0e been i+.le+ented, a +a/ .,ar+acists, and ot,er .ro0iders 7H%(8 jor barrier to o.ti+al care is a H%H9 ,a0e eac, been s,o4n to o.ti+i;e .ro0ider and tea+ be,a0ior and t,ereb3 deli0er3 s3ste+ t,at too o*ten is *rag+ented, catal3;e reduction in A%C, blood .ressure, and LDL c,olesterol. lac1s clinical in*or+ation ca.abilities, o*ten du.licates ser0ices, and is .oorl3 de/
SH )H) DIABETES CARE,
VOLU E

.ractice tea+ and an in*or+ed acti/ 0ated .atient. 7A9 K,en *easible, care s3ste+s s,ould su..ort tea+/based care, co++unit3 in0ol0e+ent, .atient registries, and e+bedded decision su..ort tools to +eet .atient needs. 7B9 Treat+ent decisions s,ould be ti+el3 and based on e0idence/based guide/ lines t,at are tailored to indi0idual .atient .re*erences, .rognoses, and co+orbidities. 7B9 A .atient/centered co++unication st3le s,ould be e+.lo3ed t,at in/ cor.orates .atient .re*erences, assesses literac3 and nu+erac3, and addresses cultural barriers to care. 7B9

4eig,t +anage+ent, e**ecti0e co.ing9, b9 disease sel*/+anage+ent 7+edication ta1ing and +anage+entO sel*/+onitoring o* glucose and blood .ressure 4,en clin/ icall3 a..ro.riate9, and c9 .re0ention o* diabetes co+.lications 7sel*/+onitoring o* *oot ,ealt,O acti0e .artici.ation in screening *or e3e, *oot, and renal co+.li/ cationsO i++uni;ations9. Dig,/-ualit3 DS E ,as been s,o4n to i+.ro0e .atient sel*/+anage+ent, satis*action, and glu/ cose control 7%E:,H%"9, as ,as deli0er3 o* ongoing DS S so t,at gains ac,ie0ed during DS E are sustained 7%!:,%!H,%H(9. $ational DS E standards call *or an integrated a..roac, t,at includes clinical content and s1ills, be,a0ioral strategies 7goal/ setting, .roble+ sol0ing9, and ad/ dressing e+otional concerns in eac, needed curriculu+ content area. Objecti0e !> C,ange t,e s3ste+ o* care T,e +ost success*ul .ractices ,a0e an in/ stitutional .riorit3 *or .ro0iding ,ig, -ual/ it3 o* care 7H%F9. C,anges t,at ,a0e been s,o4n to increase -ualit3 o* diabetes care include basing care on e0idence/ based guidelines 7H%E9, e2.anding t,e role o* tea+s and sta** 7H)%,H%B9, redesigning t,e .rocesses o* care 7H()9, i+.le+enting elec/ tronic ,ealt, record tools 7H(%,H((9, acti/ 0ating and educating .atients 7H(!,H(:9, and identi*3ing and@or de0elo.ing and en/ gaging co++unit3 resources and .ublic .olic3 t,at su..ort ,ealt,3 li*est3les 7H(H9. Recent initiati0es suc, as t,e #atient/Centered edical Do+e s,o4 .ro+ise to i+.ro0e outco+es t,roug, co/ ordinated .ri+ar3 care and o**er ne4 o./ .ortunities *or tea+/based c,ronic disease care 7H("9. Alterations in rei+burse+ent t,at re4ard t,e .ro0ision o* a..ro.riate and ,ig,/-ualit3 care rat,er t,an 0isit/ based billing 7H(F9 and t,at can acco++o/ date t,e need to .ersonali;e care goals +a3 .ro0ide additional incenti0es to i+.ro0e diabetes care 7H(E9. It is clear t,at o.ti+al diabetes +an/ age+ent re-uires an organi;ed, s3ste+/ atic a..roac, and in0ol0e+ent o* a coordinated tea+ o* dedicated ,ealt, care .ro*essionals 4or1ing in an en0iron/ +ent 4,ere .atient/centered ,ig,/ -ualit3 care is a .riorit3. o* c,ronic care. T,e CC
care.diabetesjournals.org

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Objecti0e (> Su..ort .atient be,a0ior signed *or t,e coordinated deli0er3

,as been

s,o4n in nu+erous studies to be an e**ecti0e *ra+e4or1 *or i+.ro0ing t,e -ualit3 o* diabetes care 7H))9. T,e CC includes

c,ange Success*ul diabetes care re-uires a s3s/ te+atic a..roac, to su..orting .atients< be,a0ior c,ange e**orts, including a9 ,ealt,3 li*est3le c,anges 7.,3sical acti0/ it3, ,ealt,3 eating, nonuse o* tobacco,

Re*erences %. A+erican Diabetes Association. edical anage+ent o* T3.e % Diabetes. Ale2andria, VA, A+erican Diabetes Association, ()%( (. A+erican Diabetes Association. edical anage+ent o* T3.e ( Diabetes.

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DIABETES CARE,

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Ale2andria, VA, A+erican Diabetes As/ sociation, ()%( A+erican Diabetes Association. T,era.3 *or Diabetes ellitus and Related Dis/ orders. Ale2andria, VA, A+erican Di/ abetes Association, ())B Li R, V,ang #, Bar1er LE, C,o4d,ur3 6 , V,ang U. Cost/e**ecti0eness o* in/ ter0entions to .re0ent and control di/ abetes +ellitus> a s3ste+atic re0ie4. Diabetes Care ()%)O!!>%EF(8%EB: A+erican Diabetes Association. Diagnosis and classi5cation o* diabetes +ellitus. Diabetes Care ()%)O!!7Su..l. %9>S"(8 S"B International E2.ert Co++ittee. In/ ternational E2.ert Co++ittee re.ort on t,e role o* t,e A%C assa3 in t,e diagnosis o* diabetes. Diabetes Care ())BO!(> %!(F8%!!: Vie+er DC, Qol+ #, Keintraub KS, et al. Clucose/inde.endent, blac1/ 4,ite di**erences in ,e+oglobin A%c le0els> a cross/sectional anal3sis o* ( studies. Ann Intern ed ()%)O%H(>FF)8FFF Qu+ar #R, B,ansali A, Ra0i1iran , et al. Utilit3 o* gl3cated ,e+oglobin in di/ agnosing t3.e ( diabetes +ellitus> a co++unit3/based stud3. & Clin Endo/ crinol etab ()%)OBH>(E!(8(E!H Sel0in E, Ste**es K, Ballant3ne C , Dooge0een RC, Cores, &, Brancati 6L. Racial di**erences in gl3ce+ic +ar1ers> a cross/sectional anal3sis o* co++unit3/ based data. Ann Intern ed ()%%O%H:> !)!8!)B $o4ic1a #, Santoro $, Liu D, et al. Utilit3 o* ,e+oglobin A7%c9 *or di/ agnosing .rediabetes and diabetes in obese c,ildren and adolescents. Diabetes Care ()%%O!:>%!)"8%!%% Co4ie CC, Rust Q6, B3rd/Dolt DD, et al. #re0alence o* diabetes and ,ig, ris1 *or diabetes using A%C criteria in t,e U.S. .o.ulation in %BEE/())". Diabetes Care ()%)O!!>H"(8H"E #icXn &, urri , uYo; A, 6ern ande;/Carc Za &C, Co+e;/Duelgas R, Tina,ones 6&. De+oglobin A%c 0ersus oral glucose tolerance test in .ost.artu+ diabetes screening. Diabetes Care ()%(O !H>%":E8%"H! E2.ert Co++ittee on t,e Diagnosis and Classi5cation o* Diabetes ellitus. Re/ .ort o* t,e E2.ert Co++ittee on t,e Diagnosis and Classi5cation o* Diabetes ellitus. Diabetes Care %BBFO()>%%E!8 %%BF Cenut, S, Alberti QC, Bennett #, et al.O E2.ert Co++ittee on t,e Diagnosis and Classi5cation o* Diabetes ellitus. 6ollo4/u. re.ort on t,e diagnosis o*

diabetes +ellitus. Diabetes Care ())!O (">!%")8 !%"F %H. V,ang U, Cregg EK, Killia+son D6, et al. A%C le0el and *uture ris1 o* di/ abetes> a s3ste+atic re0ie4. Diabetes Care ()%)O!!>%""H8 %"F!

%". Sel0in E, Ste**es K, V,u D, et al. Cl3/ cated ,e+oglobin, diabetes, and car/ dio0ascular ris1 in nondiabetic adults. $ Engl & ed ()%)O!"(>E))8E%% %F. Ac1er+ann RT, C,eng '&, Killia+son D6, Cregg EK. Identi*3ing adults at ,ig, ris1 *or diabetes and cardio0ascular dis/ ease using ,e+oglobin A%c $ational Dealt, and $utrition E2a+ination Sur/ 0e3 ())H/())". A+ & #re0 ed ()%%O:)> %%8%F %E. Cri*5n S&, Borc,/&o,nsen Q, Da0ies &, et al. E**ect o* earl3 intensi0e +ulti*ac/ torial t,era.3 on H/3ear cardio0ascular outco+es in indi0iduals 4it, t3.e ( di/ abetes detected b3 screening 7ADDI/ TIO$/Euro.e9> a cluster/rando+ised trial. Lancet ()%%O!FE>%H"8%"F %B. Qa,n R, Al.erin #, Edd3 D, et al. Age at initiation and *re-uenc3 o* screen/ ing to detect t3.e ( diabetes> a cost/ e**ecti0eness anal3sis. Lancet ()%)O!FH> %!"H8%!F: (). Eric1son SC, Le L, Va1,ar3an A, et al. $e4/onset treat+ent/de.endent di/ abetes +ellitus and ,3.erli.ide+ia as/ sociated 4it, at3.ical anti.s3c,otic use in older adults 4it,out sc,i;o.,renia or bi.olar disorder. & A+ Ceriatr Soc ()%(O ")>:F:8:FB (%. C,iu , Austin #C, anuel DC, S,a, BR, Tu &V. Deri0ing et,nic/s.eci5c B I cuto** .oints *or assessing diabetes ris1. Diabetes Care ()%%O!:>%F:%8%F:E ((. S,ee,3 A, #and,i $, Coursin DB, et al. inorit3 status and diabetes screening in an a+bulator3 .o.ulation. Diabetes Care ()%%O!:>%(EB8%(B: (!. Qno4ler KC, Barrett/Connor E, 6o4ler SE, et al.O Diabetes #re0ention #rogra+ Researc, Crou.. Reduction in t,e in/ cidence o* t3.e ( diabetes 4it, li*est3le inter0ention or +et*or+in. $ Engl & ed ())(O!:">!B!8:)! (:. Tuo+ile,to &, Lindstr[+ &, Eri1sson &C, et al.O 6innis, Diabetes #re0ention Stud3 Crou.. #re0ention o* t3.e ( diabetes +ellitus b3 c,anges in li*est3le a+ong subjects 4it, i+.aired glucose tolerance. $ Engl & ed ())%O!::>%!:!8%!H) (H. #an UR, Li CK, Du 'D, et al. E**ects o* diet and e2ercise in .re0enting $IDD in .eo.le 4it, i+.aired glucose toler/ ance. T,e Da Ping ICT and Diabetes Stud3. Diabetes Care %BBFO()>H!F8H:: (". Buc,anan TA, Uiang AD, #eters RQ, et al. #reser0ation o* .ancreatic beta/cell *unction and .re0ention o* t3.e ( di/ abetes b3 .,ar+acological treat+ent o* insulin resistance in ,ig,/ris1 Dis.anic 4o+en. Diabetes ())(OH%>(FB"8(E)! (F. C,iasson &L, &osse RC, Co+is R, Dane*eld , Qarasi1 A, Laa1so O STO#/ $IDD Trial Researc, Crou.. Acarbose *or .re0ention o* t3.e ( diabetes +elli/ tus> t,e STO#/$IDD rando+ised trial. Lancet ())(O!HB>()F(8()FF

(E. Cerstein DC, 'usu* S, Bosc, &, et al.O DREA 7Diabetes REduction Assess/ +ent 4it, ra+i.ril and rosiglita;one edication9 Trial In0estigators. E**ect o* rosiglita;one on t,e *re-uenc3 o* di/ abetes in .atients 4it, i+.aired glucose tolerance or i+.aired *asting glucose> a rando+ised controlled trial. Lancet ())"O!"E>%)B"8%%)H (B. Ra+ac,andran A, Sne,alat,a C, ar3 S, u1es, B, B,as1ar AD, Vija3 VO Indian Diabetes #re0ention #rogra++e 7ID##9. T,e Indian Diabetes #re0ention #ro/ gra++e s,o4s t,at li*est3le +odi5ca/ tion and +et*or+in .re0ent t3.e ( diabetes in Asian Indian subjects 4it, i+.aired glucose tolerance 7ID##/%9. Diabetologia ())"O:B>(EB8(BF !). &o,nson SL, Tabaei B#, Der+an KD. T,e e*5cac3 and cost o* alternati0e strategies *or s3ste+atic screening *or t3.e ( diabetes in t,e U.S. .o.ulation :H/F: 3ears o* age. Diabetes Care ())HO (E>!)F8!%% !%. Dabelea D, D<Agostino RB &r, a3er/ Da0is E&, et al.O SEARCD *or Diabetes in 'out, Stud3 Crou.. Testing t,e accel/ erator ,3.ot,esis> bod3 si;e, beta/cell *unction, and age at onset o* t3.e % 7autoi++une9 diabetes. Diabetes Care ())"O(B>(B)8(B: !(. Liese AD, D<Agostino RB &r, Da++an R6, et al.O SEARCD *or Diabetes in 'out, Stud3 Crou.. T,e burden o* diabetes +ellitus a+ong US 3out,> .re0alence esti+ates *ro+ t,e SEARCD *or Diabetes in 'out, Stud3. #ediatrics ())"O%%E> %H%)8%H%E !!. A+erican Diabetes Association. T3.e ( diabetes in c,ildren and adolescents. Diabetes Care ()))O(!>!E%8!EB !:. #esco0it; D, Creenbau+ C&, Qrause/ Steinrau* D, et al.O T3.e % Diabetes Trial$et Anti/CD() Stud3 Crou.. Rit/ u2i+ab, B/l3+.,oc3te de.letion, and .reser0ation o* beta/cell *unction. $ Engl & ed ())BO!"%>(%:!8(%H( !H. Orban T, Bund3 B, Bec1er D&, et al.O T3.e % Diabetes Trial$et Abatace.t Stud3 Crou.. Co/sti+ulation +odulation 4it, abatace.t in .atients 4it, recent/ onset t3.e % diabetes> a rando+ised, double/blind, .lacebo/controlled trial. Lancet ()%%O!FE>:%(8:%B !". La4rence & , Contreras R, C,en K, Sac1s DA. Trends in t,e .re0alence o* .ree2isting diabetes and gestational diabetes +ellitus a+ong a raciall3@ et,nicall3 di0erse .o.ulation o* .reg/ nant 4o+en, %BBB/())H. Diabetes Care ())EO!%>EBB8B): !F. et;ger BE, Lo4e L#, D3er AR, et al.O DA#O Stud3 Coo.erati0e Researc, Crou.. D3.ergl3ce+ia and ad0erse .regnanc3 outco+es. $ Engl & ed ())EO!HE>%BB%8())( !E. et;ger BE, Cabbe SC, #ersson B, et al.O International Association o* Diabetes

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and #regnanc3 Stud3 Crou.s Consensus #anel. International association o* di/ abetes and .regnanc3 stud3 grou.s rec/ o++endations on t,e diagnosis and classi5cation o* ,3.ergl3ce+ia in .reg/ nanc3. Diabetes Care ()%)O!!>"F"8"E( O<Sulli0an E#, A0alos C, O<Reill3 , Denned3 C, Ca**ne3 C, Dunne 6O At/ lantic DI# collaborators. Atlantic Diabetes in #regnanc3 7DI#9> t,e .re0alence and outco+es o* gestational diabetes +ellitus using ne4 diagnostic criteria. Diabetologia ()%%OH:>%"F)8%"FH La.olla A, Dal*r\ C, Raga;;i E, De Cata A#, 6edele D. $e4 International Asso/ ciation o* t,e Diabetes and #regnanc3 Stud3 Crou.s 7IAD#SC9 reco++en/ dations *or diagnosing gestational di/ abetes co+.ared 4it, *or+er criteria> a retros.ecti0e stud3 on .regnanc3 out/ co+e. Diabet ed ()%%O(E>%)F:8%)FF Landon B, S.ong C', T,o+ E, et al.O Eunice Qenned3 S,ri0er $ational In/ stitute o* C,ild Dealt, and Du+an De/ 0elo.+ent aternal/6etal edicine Units $et4or1. A +ulticenter, rando+/ i;ed trial o* treat+ent *or +ild gesta/ tional diabetes. $ Engl & ed ())BO!"%> %!!B8%!:E Cro4t,er CA, Diller &E, oss &R, c#,ee A&, &e**ries KS, Robinson &SO Australian Carbo,3drate Intolerance Stud3 in #regnant Ko+en 7ACDOIS9 Trial Crou.. E**ect o* treat+ent o* ges/ tational diabetes +ellitus on .regnanc3 outco+es. $ Engl & ed ())HO!H(> (:FF8(:E" Co++ittee on Obstetric #ractice. Co+/ +ittee o.inion no. H):> screening and diagnosis o* gestational diabetes +elli/ tus. Obstet C3necol ()%%O%%E>FH%8FH! Qi+ C, Der+an KD, C,eung $K, Cunderson E#, Ric,ardson C. Co+.ar/ ison o* ,e+oglobin A%c 4it, *asting .las+a glucose and (/, .ostc,allenge glucose *or ris1 strati5cation a+ong 4o+en 4it, recent gestational diabetes +ellitus. Diabetes Care ()%%O!:>%B:B8 %BH% Qi+ C, $e4ton Q , Qno.. RD. Cesta/ tional diabetes and t,e incidence o* t3.e ( diabetes> a s3ste+atic re0ie4. Diabetes Care ())(O(H>%E"(8%E"E Tobias DQ, Du 6B, C,a0arro &, Rosner B, o;a**arian D, V,ang C. Dealt,*ul di/ etar3 .atterns and t3.e ( diabetes +el/ litus ris1 a+ong 4o+en 4it, a ,istor3 o* gestational diabetes +ellitus. Arc, Intern ed ()%(O%F(>%H""8%HF( Li C, V,ang #, Kang &, et al. T,e long/ ter+ e**ect o* li*est3le inter0entions to .re0ent diabetes in t,e C,ina Da Ping Diabetes #re0ention Stud3> a ()/3ear *ollo4/u. stud3. Lancet ())EO!F%>%FE!8%FEB Lindstr[+ &, Ilanne/#ari11a #, #eltonen , et al.O 6innis, Diabetes #re0ention

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inter0ention> *ollo4/u. o* t,e 6innis, Diabetes #re0ention Stud3. Lancet ())"O !"E>%"F!8%"FB :B. Qno4ler KC, 6o4ler SE, Da++an R6, et al.O Diabetes #re0ention #rogra+ Re/ searc, Crou.. %)/3ear *ollo4/u. o* di/ abetes incidence and 4eig,t loss in t,e Diabetes #re0ention #rogra+ Outco+es Stud3. Lancet ())BO!F:>%"FF8%"E" H). Der+an KD, Doerger T&, Brandle , et al.O Diabetes #re0ention #rogra+ Re/ searc, Crou.. T,e cost/e**ecti0eness o* li*est3le +odi5cation or +et*or+in in .re0enting t3.e ( diabetes in adults 4it, i+.aired glucose tolerance. Ann Intern ed ())HO%:(>!(!8!!( H%. Diabetes #re0ention #rogra+ Researc, Crou.. T,e %)/3ear cost/e**ecti0eness o* li*est3le inter0ention or +et*or+in *or diabetes .re0ention> an intent/to/treat anal3sis o* t,e D##@D##OS. Diabetes Care ()%(O!H>F(!8F!) H(. Ac1er+ann RT, 6inc, EA, Bri;endine E, V,ou D, arrero DC. Translating t,e Diabetes #re0ention #rogra+ into t,e co++unit3. T,e DE#LO' #ilot Stud3. A+ & #re0 ed ())EO!H>!HF8!"! H!. Diabetes #re0ention #rogra+ Researc, Crou.. Long/ter+ sa*et3, tolerabilit3, and 4eig,t loss associated 4it, +et*or/ +in in t,e Diabetes #re0ention #rogra+ Outco+es Stud3. Diabetes Care ()%(O !H>F!%8F!F H:. DREA Trial In0estigators. Incidence o* diabetes *ollo4ing ra+i.ril or rosiglita/ ;one 4it,dra4al. Diabetes Care ()%%O !:>%("H8%("B HH. Ratner RE, C,risto.,i CA, et;ger BE, et al.O Diabetes #re0ention #rogra+ Re/ searc, Crou.. #re0ention o* diabetes in 4o+en 4it, a ,istor3 o* gestational di/ abetes> e**ects o* +et*or+in and li*est3le inter0entions. & Clin Endocrinol etab ())EOB!>:FF:8:FFB H". Orc,ard T&, Te+.rosa , Barrett/ Connor E, et al.O T,e Diabetes #re/ 0ention #rogra+ Outco+es Stud3 Researc, Crou.O .re.ared on be,al* o* t,e D##OS Researc, Crou.. Long/ter+ e**ects o* t,e Diabetes #re0ention #ro/ gra+ inter0entions on cardio0ascular ris1 *actors> a re.ort *ro+ t,e D## Out/ co+es Stud3. Diabet ed. %B &ul3 ()%( LE.ub a,ead o* .rintM HF. Viegler R, Deidt+ann B, Dilgard D, Do*er S, Rosenbauer &, Doll RO D#V/ Kiss/Initiati0e. 6re-uenc3 o* S BC correlates 4it, DbA%c and acute co+/ .lications in c,ildren and adolescents 4it, t3.e % diabetes. #ediatr Diabetes ()%%O%(>%%8%F HE. 6ar+er A, Kade A, Co3der E, et al. I+/ .act o* sel* +onitoring o* blood glucose in t,e +anage+ent o* .atients 4it, non/ insulin treated diabetes> o.en .arallel grou. rando+ised trial. B & ())FO!!H> %!(

HB. O<Qane &, Bunting B, Co.eland , Coates VEO ES O$ Stud3 Crou.. E*5/ cac3 o* sel* +onitoring o* blood glucose in .atients 4it, ne4l3 diagnosed t3.e ( diabetes 7ES O$ stud39> rando+ised controlled trial. B & ())EO!!">%%F:8 %%FF "). Si+on &, Cra3 A, Clar1e #, Kade A, $eil A, 6ar+er AO Diabetes Cl3cae+ic Edu/ cation and onitoring Trial Crou.. Cost e**ecti0eness o* sel* +onitoring o* blood glucose in .atients 4it, non/insulin treated t3.e ( diabetes> econo+ic e0al/ uation o* data *ro+ t,e DiCE trial. B & ())EO!!">%%FF8%%E) "%. 6ar+er A&, #erera R, Kard A, et al. eta/ anal3sis o* indi0idual .atient data in rando+ised trials o* sel* +onitoring o* blood glucose in .eo.le 4it, non/ insulin treated t3.e ( diabetes. B & ()%(O!::>e:E" "(. alanda UL, Kelsc,en L C, Ri.,agen II, De11er & , $ij.els C, Bot SD. Sel*/ +onitoring o* blood glucose in .atients 4it, t3.e ( diabetes +ellitus 4,o are not using insulin. Coc,rane Database S3st Re0 ()%(O()%(7Issue %9>CD))H)") "!. Sac1s DB, Arnold , Ba1ris CL, et al.O $ational Acade+3 o* Clinical Bio/ c,e+istr3. #osition state+ent e2ecuti0e su++ar3> guidelines and reco++enda/ tions *or laborator3 anal3sis in t,e di/ agnosis and +anage+ent o* diabetes +ellitus. Diabetes Care ()%%O!:>%:%B8 %:(! ":. Kang &, Vgibor &, att,e4s &T, C,arron/ #roc,o4ni1 D, Serei1a S , Si+inerio L. Sel*/+onitoring o* blood glucose is as/ sociated 4it, .roble+/sol0ing s1ills in ,3.ergl3ce+ia and ,3.ogl3ce+ia. Di/ abetes Educ ()%(O!E>()F8(%E "H. #olons13 KD, 6is,er L, Sc,i1+an CD, et al. Structured sel*/+onitoring o* blood glucose signi5cantl3 reduces A%C le0els in .oorl3 controlled, noninsulin/treated t3.e ( diabetes> results *ro+ t,e Struc/ tured Testing #rogra+ stud3. Diabetes Care ()%%O!:>("(8("F "". Ta+borlane KV, Bec1 RK, Bode BK, et al.O &u0enile Diabetes Researc, 6oun/ dation Continuous Clucose onitor/ ing Stud3 Crou.. Continuous glucose +onitoring and intensi0e treat+ent o* t3.e % diabetes. $ Engl & ed ())EO!HB> %:":8%:F" "F. Bec1 RK, Dirsc, IB, La**el L, et al.O &u/ 0enile Diabetes Researc, 6oundation Continuous Clucose onitoring Stud3 Crou.. T,e e**ect o* continuous glucose +onitoring in 4ell/controlled t3.e % diabetes. Diabetes Care ())BO!(>%!FE8 %!E! "E. Bergenstal R , Ta+borlane KV, A,+ann A, et al.O STAR ! Stud3 Crou.. E**ecti0eness o* sensor/aug+ented in/ sulin/.u+. t,era.3 in t3.e % diabetes. $ Engl & ed ()%)O!"!>!%%8!()

"B. Slo0er RD, Kels, &B, Criego A, et al. E**ecti0eness o* sensor/aug+ented .u+. t,era.3 in c,ildren and adolescents 4it, t3.e % diabetes in t,e STAR ! stud3. #e/ diatr Diabetes ()%(O%!>"8%% F). 'e, DC, Bro4n TT, arut,ur $, et al. Co+.arati0e e**ecti0eness and sa*et3 o* +et,ods o* insulin deli0er3 and glucose +onitoring *or diabetes +ellitus> a s3s/ te+atic re0ie4 and +eta/anal3sis. Ann Intern ed ()%(O%HF>!!"8!:F F%. T,e Diabetes Control and Co+.lications Trial Researc, Crou.. T,e e**ect o* in/ tensi0e treat+ent o* diabetes on t,e de/ 0elo.+ent and .rogression o* long/ter+ co+.lications in insulin/de.endent di/ abetes +ellitus. $ Engl & ed %BB!O!(B> BFF8BE" F(. Stratton I , Adler AI, $eil DA, et al. Association o* gl3cae+ia 4it, +acro/ 0ascular and +icro0ascular co+.lica/ tions o* t3.e ( diabetes 7UQ#DS !H9> .ros.ecti0e obser0ational stud3. B & ()))O!(%>:)H8:%( F!. Cagliero E, Le0ina EV, $at,an D . I+/ +ediate *eedbac1 o* DbA%c le0els i+/ .ro0es gl3ce+ic control in t3.e % and insulin/treated t3.e ( diabetic .atients. Diabetes Care %BBBO((>%FEH8%FEB F:. iller CD, Barnes CS, #,illi.s LS, et al. Ra.id A%c a0ailabilit3 i+.ro0es clinical decision/+a1ing in an urban .ri+ar3 care clinic. Diabetes Care ())!O(">%%HE8 %%"! FH. Al/Ansar3 L, 6ar+er A, Dirst &, et al. #oint/o*/care testing *or Db A%c in t,e +anage+ent o* diabetes> a s3ste+atic re0ie4 and +etaanal3sis. Clin C,e+ ()%%OHF>H"E8HF" F". Ciala+as A, St &o,n A, Laurence CO, Bubner TQO #oCT anage+ent Co+/ +ittee. #oint/o*/care testing *or .atients 4it, diabetes, ,3.erli.idae+ia or co/ agulation disorders in t,e general .rac/ tice setting> a s3ste+atic re0ie4. 6a+ #ract ()%)O(F>%F8(: FF. $at,an D , Quenen &, Borg R, V,eng D, Sc,oen*eld D, Deine R&O A%C/Deri0ed A0erage Clucose Stud3 Crou.. Trans/ lating t,e A%C assa3 into esti+ated a0/ erage glucose 0alues. Diabetes Care ())EO!%>%:F!8%:FE FE. Ro,l5ng CL, Kied+e3er D , Little RR, England &D, Tennill A, Coldstein DE. De5ning t,e relations,i. bet4een .las+a glucose and DbA7%c9> anal3sis o* glucose .ro5les and DbA7%c9 in t,e Di/ abetes Control and Co+.lications Trial. Diabetes Care ())(O(H>(FH8(FE FB. Kilson D , Qoll+anO Diabetes Researc, in C,ildren $et4or1 7Direc$et9 Stud3 Crou.. Relations,i. o* A%C to glucose concentrations in c,ildren 4it, t3.e % diabetes> assess+ents b3 ,ig,/*re-uenc3 glucose deter+inations b3 sensors. Di/ abetes Care ())EO!%>!E%8!EH

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intensi0e glucose lo4ering in t3.e ( di/ abetes. $ Engl & ed ())EO!HE>(H:H8 (HHB $at,an D , Clear3 #A, Bac1lund &', et al.O Diabetes Control and Co+.li/ cations Trial@E.ide+iolog3 o* Diabetes Inter0entions and Co+.lications 7DCCT@ EDIC9 Stud3 Researc, Crou.. Intensi0e diabetes treat+ent and cardio0ascular disease in .atients 4it, t3.e % diabetes. $ Engl & ed ())HO!H!>(":!8("H! $at,an D , Vin+an B, Clear3 #A, et al.O Diabetes Control and Co+.lications Trial@E.ide+iolog3 o* Diabetes Inter/ 0entions and Co+.lications 7DCCT@ EDIC9 Researc, Crou.. odern/da3 clinical course o* t3.e % diabetes +ellitus a*ter !) 3ears< duration> t,e Diabetes Con/ trol and Co+.lications Trial@E.ide+iolog3 o* Diabetes Inter0entions and Co+.lica/ tions and #ittsburg, E.ide+iolog3 o* Diabetes Co+.lications e2.erience 7%BE!/ ())H9. Arc, Intern ed ())BO%"B>%!)F8 %!%" S13ler &S, Bergenstal R, Bono4 RO, et al.O A+erican Diabetes AssociationO A+eri/ can College o* Cardiolog3 6oundationO A+erican Deart Association. Intensi0e gl3ce+ic control and t,e .re0ention o* cardio0ascular e0ents> i+.lications o* t,e ACCORD, ADVA$CE, and VA Di/ abetes Trials> a .osition state+ent o* t,e A+erican Diabetes Association and a scienti5c state+ent o* t,e A+erican College o* Cardiolog3 6oundation and t,e A+erican Deart Association. Di/ abetes Care ())BO!(>%EF8%B( Cerstein DC, iller E, Cenut, S, et al.O ACCORD Stud3 Crou.. Long/ter+ e*/ *ects o* intensi0e glucose lo4ering on cardio0ascular outco+es. $ Engl & ed ()%%O!":>E%E8E(E Riddle C, A+brosius KT, Brillon D&, et al.O Action to Control Cardio0ascular Ris1 in Diabetes In0estigators. E.ide+i/ ologic relations,i.s bet4een A%C and all/cause +ortalit3 during a +edian !.:/ 3ear *ollo4/u. o* gl3ce+ic treat+ent in t,e ACCORD trial. Diabetes Care ()%)O !!>BE!8BB) Bonds DE, iller E, Bergenstal R , et al. T,e association bet4een s3+./ to+atic, se0ere ,3.ogl3cae+ia and +ortalit3 in t3.e ( diabetes> retros.ec/ ti0e e.ide+iological anal3sis o* t,e AC/ CORD stud3. B & ()%)O!:)>b:B)B Rea0en #D, orit; TE, Sc,4en1e DC, et al. Intensi0e glucose/lo4ering t,era.3 reduces cardio0ascular disease e0ents in Veterans A**airs Diabetes Trial .artici.ants 4it, lo4er calci5ed coronar3 at,eroscle/ rosis. Diabetes ())BOHE>(":(8(":E Duc14ort, KC, Abraira C, orit; TE, et al.O In0estigators o* t,e VADT. T,e duration o* diabetes a**ects t,e res.onse to intensi0e glucose control in t3.e ( subjects> t,e VA Diabetes Trial.

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& Diabetes Co+.lications ()%%O(H>!HH8 !"% Turnbull 6 , Abraira C, Anderson R&, et al.O Control Crou.. Intensi0e glucose control and +acro0ascular outco+es in t3.e ( diabetes. Diabetologia ())BOH(> ((EE8((BE Is+ail/Beigi 6, og,issi E, Ti1tin , Dirsc, IB, In;ucc,i SE, Cenut, S. In/ di0iduali;ing gl3ce+ic targets in t3.e ( diabetes +ellitus> i+.lications o* recent clinical trials. Ann Intern ed ()%%O%H:> HH:8HHB A+erican Diabetes Association. #ost/ .randial blood glucose. Diabetes Care ())%O(:>FFH8FFE Ceriello A, Taboga C, Tonutti L, et al. E0idence *or an inde.endent and cu/ +ulati0e e**ect o* .ost.randial ,3.er/ trigl3ceride+ia and ,3.ergl3ce+ia on endot,elial d3s*unction and o2idati0e stress generation> e**ects o* s,ort/ and long/ter+ si+0astatin treat+ent. Circu/ lation ())(O%)">%(%%8%(%E Ra; I, Kilson #K, Stroje1 Q, et al. E**ects o* .randial 0ersus *asting gl3ce+ia on cardio0ascular outco+es in t3.e ( di/ abetes> t,e DEART(D trial. Diabetes Care ())BO!(>!E%8!E" et;ger BE, Buc,anan TA, Coustan DR, et al. Su++ar3 and reco++endations o* t,e 6i*t, International Kor1s,o./ Con*erence on Cestational Diabetes ellitus. Diabetes Care ())FO!)7Su..l. (9>S(H%8S(") Qit;+iller &L, Bloc1 & , Bro4n 6 , et al. anaging .ree2isting diabetes *or .r/ egnanc3> su++ar3 o* e0idence and consensus reco++endations *or care. Diabetes Care ())EO!%>%)")8%)FB DeKitt DE, Dirsc, IB. Out.atient in/ sulin t,era.3 in t3.e % and t3.e ( di/ abetes +ellitus> scienti5c re0ie4. &A A ())!O(EB>((H:8((": Rosenstoc1 &, Daile3 C, assi/Benedetti , 6ritsc,e A, Lin V, Sal;+an A. Re/ duced ,3.ogl3ce+ia ris1 4it, insulin glargine> a +eta/anal3sis co+.aring in/ sulin glargine 4it, ,u+an $#D insulin in t3.e ( diabetes. Diabetes Care ())HO (E>BH)8BHH A+erican Diabetes Association. Intensi0e Diabetes anage+ent. Ale2andria, VA, A+erican Diabetes Association, ())B ooradian AD, Bernbau+ , Albert SC. $arrati0e re0ie4> a rational a..roac, to starting insulin t,era.3. Ann Intern ed ())"O%:H>%(H8%!: In;ucc,i SE, Bergenstal R , Buse &B, et al.O A+erican Diabetes Association 7ADA9O Euro.ean Association *or t,e Stud3 o* Diabetes 7EASD9. anage+ent o* ,3.ergl3ce+ia in t3.e ( diabetes> a .atient/centered a..roac,. #osition State+ent o* t,e A+erican Diabetes As/ sociation 7ADA9 and t,e Euro.ean As/ sociation *or t,e Stud3 o* Diabetes

7EASD9. Diabetes Care ()%(O!H>%!":8 %!FB %%(. Bennett KL, arut,ur $ , Sing, S, et al. Co+.arati0e e**ecti0eness and sa*et3 o* +edications *or t3.e ( diabetes> an u.date including ne4 drugs and (/ drug co+binations. Ann Intern ed ()%%O%H:>")(8"%! %%!. Blonde L, erilainen , Qar4e V, Ras1in #O TITRATE Stud3 Crou.. #atient/di/ rected titration *or ac,ie0ing gl3cae+ic goals using a once/dail3 basal insulin analogue> an assess+ent o* t4o di**erent *asting .las+a glucose targets8t,e TITRATE stud3. Diabetes Obes etab ())BO%%>"(!8"!% %%:. Bantle &#, K3lie/Rosett &, Albrig,t AL, et al.O A+erican Diabetes Association. $utrition reco++endations and inter/ 0entions *or diabetes> a .osition state+ent o* t,e A+erican Diabetes Association. Diabetes Care ())EO!%7Su..l. %9>S"%8 SFE %%H. DA6$E Stud3 Crou.. Training in Ae2i/ ble, intensi0e insulin +anage+ent to enable dietar3 *reedo+ in .eo.le 4it, t3.e % diabetes> dose adjust+ent *or nor+al eating 7DA6$E9 rando+ised controlled trial. B & ())(O!(H>F:" %%". 6ran; &, on1 A, Barr3 B, et al. E**ec/ ti0eness o* +edical nutrition t,era.3 .ro0ided b3 dietitians in t,e +anage/ +ent o* non/insulin/de.endent diabetes +ellitus> a rando+i;ed, controlled clinical trial. & A+ Diet Assoc %BBHOBH>%))B8 %)%F %%F. Cold,aber/6iebert &D, Cold,aber/6iebert S$, Trist an L, $at,an D . Rando+i;ed controlled co++unit3/ based nutrition and e2ercise inter0ention i+.ro0es gl3/ ce+ia and cardio0ascular ris1 *actors in t3.e ( diabetic .atients in rural Costa Rica. Diabetes Care ())!O(">(:8(B %%E. Le+on CC, Lace3 Q, Lo,se B, Dubac,er DO, Qla4itter B, #alta . Outco+es +onitoring o* ,ealt,, be,a0ior, and -ualit3 o* li*e a*ter nutrition inter0ention in adults 4it, t3.e ( diabetes. & A+ Diet Assoc ()):O%):>%E)H8%E%H %%B. iller CQ, Ed4ards L, Qissling C, San0ille L. $utrition education i+.ro0es +etabolic outco+es a+ong older adults 4it, diabetes +ellitus> results *ro+ a rando+i;ed controlled trial. #re0 ed ())(O!:>(H(8(HB %(). Kilson C, Bro4n T, Acton Q, Cilliland S. E**ects o* clinical nutrition education and educator disci.line on gl3ce+ic control outco+es in t,e Indian Dealt, Ser0ice. Diabetes Care ())!O(">(H))8 (H): %(%. Craber AL, Elas3 TA, Puinn D, Kol** Q, Bro4n A. I+.ro0ing gl3ce+ic control in adults 4it, diabetes +ellitus> s,ared re/

s.onsibilit3 in .ri+ar3 care .ractices. Sout, ed & ())(OBH>"E:8"B) %((. Caet1e L , Stuart A, Trus;c;3ns1a D. A single nutrition counseling session

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4it, a registered dietitian i+.ro0es s,ort/ter+ clinical outco+es *or rural Qentuc13 .atients 4it, c,ronic diseases. & A+ Diet Assoc ())"O%)">%)B8%%( Van Dorn L, cCoin , Qris/Et,erton # , et al. T,e e0idence *or dietar3 .re/ 0ention and treat+ent o* cardio0ascular disease. & A+ Diet Assoc ())EO%)E>(EF8 !!% A..el L&, oore T&, Obar;ane1 E, et al.O DASD Collaborati0e Researc, Crou.. A clinical trial o* t,e e**ects o* dietar3 .at/ terns on blood .ressure. $ Engl & ed %BBFO!!">%%%F8%%(: 6ran; &, VanKor+er &&, Crain AL, et al. Keig,t/loss outco+es> a s3ste+atic re0ie4 and +eta/anal3sis o* 4eig,t/ loss clinical trials 4it, a +ini+u+ %/3ear *ollo4/u.. & A+ Diet Assoc ())FO%)F>%FHH8%F"F 6oster CD, K3att DR, Dill &O, et al. A rando+i;ed trial o* a lo4/carbo,3drate diet *or obesit3. $ Engl & ed ())!O!:E> ()E(8()B) Stern L, I-bal $, Ses,adri #, et al. T,e e**ects o* lo4/carbo,3drate 0ersus con/ 0entional 4eig,t loss diets in se0erel3 obese adults> one/3ear *ollo4/u. o* a rando+i;ed trial. Ann Intern ed ()):O %:)>FFE8FEH 6oster CD, K3att DR, Dill &O, et al. Keig,t and +etabolic outco+es a*ter ( 3ears on a lo4/carbo,3drate 0ersus lo4/ *at diet> a rando+i;ed trial. Ann Intern ed ()%)O%H!>%:F8%HF S,ai I, Sc,4ar;*uc,s D, Den1in ', et al.O Dietar3 Inter0ention Rando+i;ed Con/ trolled Trial 7DIRECT9 Crou.. Keig,t loss 4it, a lo4/carbo,3drate, editer/ ranean, or lo4/*at diet. $ Engl & ed ())EO!HB>((B8(:% $ord+ann A&, $ord+ann A, Briel , et al. E**ects o* lo4/carbo,3drate 0s lo4/ *at diets on 4eig,t loss and cardio0as/ cular ris1 *actors> a +eta/anal3sis o* rando+i;ed controlled trials. Arc, In/ tern ed ())"O%"">(EH8(B! $orris SL, V,ang U, A0enell A, et al. Long/ter+ e**ecti0eness o* 4eig,t/loss inter0entions in adults 4it, .re/ diabetes> a re0ie4. A+ & #re0 ed ())HO (E>%("8%!B Salas/Sal0ado &, Bullo , Babio $, et al. Reduction in t,e incidence o* t3.e ( di/ abetes 4it, t,e editerranean diet> re/ sults o* t,e #REDI ED/Reus nutrition inter0ention rando+i;ed trial. Diabetes Care ()%%O!:>%:8%B ali1 VS, #o.1in B , Bra3 CA, Des.r]s &#, Killett KC, Du 6B. Sugar/ s4eetened be0erages and ris1 o* +etabolic s3n/ dro+e and t3.e ( diabetes> a +eta/ anal3sis. Diabetes Care ()%)O!!> (:FF8(:E! Qlein S, S,eard $6, #i/Sun3er U, et al.O A+erican Diabetes AssociationO $ort,

A+erican Association *or t,e Stud3 o* Obesit3O A+erican Societ3 *or Clinical $utrition. Keig,t +anage+ent t,roug,

li*est3le +odi5cation *or t,e .re0ention and +anage+ent o* t3.e ( diabetes> ra/ tionale and strategies. A state+ent o* t,e A+erican Diabetes Association, t,e $ort, A+erican Association *or t,e Stud3 o* Obesit3, and t,e A+erican So/ ciet3 *or Clinical $utrition. Diabetes Care ()):O(F>()"F8()F! %!H. $orris SL, V,ang U, A0enell A, et al. E*/ 5cac3 o* .,ar+acot,era.3 *or 4eig,t loss in adults 4it, t3.e ( diabetes +el/ litus> a +eta/anal3sis. Arc, Intern ed ()):O%":>%!BH8%:): %!". Kol* A , Cona4a3 R, Cro4t,er &P, et al.O Translating li*est3le inter0ention to .ractice in obese .atients 4it, t3.e ( diabetes> I+.ro0ing Control 4it, Ac/ ti0it3 and $utrition 7ICA$9 stud3. Di/ abetes Care ()):O(F>%HF)8%HF" %!F. anning R , &ung RT, Leese C#, $e4ton RK. T,e co+.arison o* *our 4eig,t reduction strategies ai+ed at o0er4eig,t .atients 4it, diabetes +elli/ tus> *our/3ear *ollo4/u.. Diabet ed %BBEO%H>:BF8H)( %!E. #i/Sun3er U, Blac1burn C, Brancati 6L, et al.O Loo1 ADEAD Researc, Crou.. Reduction in 4eig,t and cardio0ascular disease ris1 *actors in indi0iduals 4it, t3.e ( diabetes> one/3ear results o* t,e loo1 ADEAD trial. Diabetes Care ())FO !)>%!F:8%!E! %!B. King RRO Loo1 ADEAD Researc, Crou.. Long/ter+ e**ects o* a li*est3le inter0ention on 4eig,t and cardio0as/ cular ris1 *actors in indi0iduals 4it, t3.e ( diabetes +ellitus> *our/3ear results o* t,e Loo1 ADEAD trial. Arc, Intern ed ()%)O%F)>%H""8%HFH %:). K,eeler L, Dunbar SA, &aac1s L , et al. acronutrients, *ood grou.s, and eating .atterns in t,e +anage+ent o* diabetes> a s3ste+atic re0ie4 o* t,e lit/ erature, ()%). Diabetes Care ()%(O!H> :!:8::H %:%. Es.osito Q, aiorino I, Ciotola , et al. E**ects o* a editerranean/st3le diet on t,e need *or anti,3.ergl3ce+ic drug t,era.3 in .atients 4it, ne4l3 di/ agnosed t3.e ( diabetes> a rando+i;ed trial. Ann Intern ed ())BO%H%>!)"8 !%: %:(. Barnard $D, Co,en &, &en1ins D&, et al. A lo4/*at 0egan diet i+.ro0es gl3ce+ic control and cardio0ascular ris1 *actors in a rando+i;ed clinical trial in in/ di0iduals 4it, t3.e ( diabetes. Diabetes Care ())"O(B>%FFF8%FE! %:!. Turner/ cCrie03 C , Barnard $D, Co,en &, &en1ins D&, Cloede L, Creen AA. C,anges in nutrient inta1e and di/ etar3 -ualit3 a+ong .artici.ants 4it, t3.e ( diabetes *ollo4ing a lo4/*at 0egan diet or a con0entional diabetes diet *or (( 4ee1s. & A+ Diet Assoc ())EO%)E> %"!"8%":H

%::. Institute o* edicine. Dietar3 Re*erence Inta1es> Energ3, Carbo,3drate, 6iber, 6at,

6att3 Acids, C,olesterol, #rotein, and A+ino Acids. Kas,ington, DC, $ational Acade+ies #ress, ())( %:H. 6ran; &, Bantle &#, Beebe CA, et al. E0idence/based nutrition .rinci.les and reco++endations *or t,e treat+ent and .re0ention o* diabetes and related co+/ .lications. Diabetes Care ())(O(H>%:E8 %BE %:". $orris SL, Engelgau , $ara3an Q . E**ecti0eness o* sel*/+anage+ent train/ ing in t3.e ( diabetes> a s3ste+atic re/ 0ie4 o* rando+i;ed controlled trials. Diabetes Care ())%O(:>H"%8HEF %:F. $orris SL, Lau &, S+it, S&, Sc,+id CD, Engelgau . Sel*/+anage+ent educa/ tion *or adults 4it, t3.e ( diabetes> a +eta/ anal3sis o* t,e e**ect on gl3ce+ic control. Diabetes Care ())(O(H>%%HB8%%F% %:E. Car3 TL, Cen1inger & , Cuallar E, #e3rot , Brancati 6L. eta/anal3sis o* rando+i;ed educational and be,a0ioral inter0entions in t3.e ( diabetes. Diabetes Educ ())!O(B>:EE8H)% %:B. Steed L, Coo1e D, $e4+an S. A s3ste+atic re0ie4 o* .s3c,osocial outco+es *ollo4ing education, sel*/+anage+ent and .s3c,o/ logical inter0entions in diabetes +ellitus. #atient Educ Couns ())!OH%>H8%H %H). Ellis SE, S.ero** T, Dittus RS, Bro4n A, #ic,ert &K, Elas3 TA. Diabetes .atient education> a +eta/anal3sis and +eta/ regression. #atient Educ Couns ()):OH(> BF8%)H %H%. Karsi A, Kang #S, LaValle3 #, A0orn &, Solo+on DD. Sel*/+anage+ent educa/ tion .rogra+s in c,ronic disease> a s3s/ te+atic re0ie4 and +et,odological criti-ue o* t,e literature. Arc, Intern ed ()):O%":>%":%8%":B %H(. Daas L, ar3niu1 , Bec1 &, et al.O on be,al* o* t,e ()%( Standards Re0ision Tas1 6orce. $ational Standards *or Di/ abetes Sel*/ anage+ent Education and Su..ort. Diabetes Care ()%(O!H>(!B!8 (:)% %H!. ulca,3 Q, ar3niu1 , #ee.les , et al. Diabetes sel*/+anage+ent educa/ tion core outco+es +easures. Diabetes Educ ())!O(B>F"E8E)! %H:. Clasgo4 RE, #ee.les , S1o0lund SE. K,ere is t,e .atient in diabetes .er*or/ +ance +easures^ T,e case *or including .atient/centered and sel*/+anage+ent +easures. Diabetes Care ())EO!%>%):"8 %)H) %HH. Bar1er & , Coe,rig SD, Barriga Q, et al.O DAIS' stud3. Clinical c,aracteristics o* c,ildren diagnosed 4it, t3.e % diabetes t,roug, intensi0e screening and *ollo4/ u.. Diabetes Care ()):O(F>%!BB8%:): %H". Deinric, E, Sc,a.er $C, de Vries $Q. Sel*/+anage+ent inter0entions *or t3.e ( diabetes> a s3ste+atic re0ie4. Eur Di/ abetes $urs ()%)OF>F%8F" %HF. 6rosc, DL, U3 V, Oc,oa S, angione C . E0aluation o* a be,a0ior su..ort inter0ention *or .atients 4it, .oorl3

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controlled diabetes. Arc, Intern ed ()%%O%F%>()%%8()%F cCo4an #. T,e e*5cac3 o* diabetes .atient education and sel*/+anage+ent education in t3.e ( diabetes. Can & Di/ abetes ()%%O!H>:"8H! Coc,ran &, Conn VS. eta/anal3sis o* -ualit3 o* li*e outco+es *ollo4ing di/ abetes sel*/+anage+ent training. Di/ abetes Educ ())EO!:>E%H8E(! 6is,er EB, T,or.e CT, De0ellis B , De0ellis R6. Dealt,3 co.ing, negati0e e+otions, and diabetes +anage+ent> a s3ste+atic re0ie4 and a..raisal. Di/ abetes Educ ())FO!!>%)E)8%%)!O dis/ cussion %%):8%%)" Robbins & , T,atc,er CE, Kebb DA, Vald+anis VC. $utritionist 0isits, di/ abetes classes, and ,os.itali;ation rates and c,arges> t,e Urban Diabetes Stud3. Diabetes Care ())EO!%>"HH8"") #olons13 KD, Earles &, S+it, S, et al. Integrating +edical +anage+ent 4it, diabetes sel*/+anage+ent training> a ran/ do+i;ed control trial o* t,e Diabetes Out.atient Intensi0e Treat+ent .rogra+. Diabetes Care ())!O(">!):E8 !)H! #iatt CA, Anderson R , Broo1s , et al. !/3ear *ollo4/u. o* clinical and be,a0ioral i+.ro0e+ents *ollo4ing a +ulti*aceted diabetes care inter0ention> results o* a rando+i;ed controlled trial. Diabetes Educ ()%)O!">!)%8!)B Tang TS, 6unnell , Bro4n B, Qurlander &E. Sel*/+anage+ent su..ort in =real/4orld? settings> an e+.o4er/ +ent/based inter0ention. #atient Educ Couns ()%)OFB>%FE8%E: Renders C , Val1 CD, Cri*5n S, Kagner ED, Eij1 &T, Assendel*t K&. Inter0entions to i+.ro0e t,e +anage+ent o* diabetes +ellitus in .ri+ar3 care, out.atient and co++unit3 settings. Coc,rane Database S3st Re0 ())%O7%9>CD))%:E% Cla;ier RD, Bajcar &, Qennie $R, Killson Q. A s3ste+atic re0ie4 o* inter0entions to i+.ro0e diabetes care in sociall3 dis/ ad0antaged .o.ulations. Diabetes Care ())"O(B>%"FH8%"EE Da4t,orne Q, Robles ', Cannings/&o,n R, Ed4ards AC. Culturall3 a..ro.riate ,ealt, education *or t3.e ( diabetes +ellitus in et,nic +inorit3 grou.s. Co/ c,rane Database S3st Re0 ())EO7!9> CD))":(: Sar1isian CA, Bro4n A6, $orris QC, Kint; RL, angione C . A s3ste+atic re0ie4 o* diabetes sel*/care inter0entions *or older, A*rican A+erican, or Latino adults. Diabetes Educ ())!O(B>:"F8 :FB C,odos, &, orton SC, ojica K, et al. eta/anal3sis> c,ronic disease sel*/ +anage+ent .rogra+s *or older adults. Ann Intern ed ())HO%:!>:(F8:!E

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a conce.tual re0ie4. Diabetes Care ())FO!)>(:!!8(::) Anderson DR, C,ristison/Lega3 &, #roctor/Cra3 E. Sel*/ anage+ent goal setting in a co++unit3 ,ealt, center> t,e i+.act o* goal attain+ent on diabetes outco+es. Diabetes S.ectru+ ()%)O(!> BF8%)" Dea1in T, cS,ane CE, Cade &E, Killia+s RD. Crou. based training *or sel*/+anage+ent strategies in .eo.le 4it, t3.e ( diabetes +ellitus. Coc,rane Database S3st Re0 ())HO7(9>CD))!:%F Du1e SA, Colagiuri S, Colagiuri R. In/ di0idual .atient education *or .eo.le 4it, t3.e ( diabetes +ellitus. Coc,rane Database S3st Re0 ())BO7%9>CD))H("E Deisler , Vijan S, a11i 6, #iette &D. Diabetes control 4it, reci.rocal .eer su..ort 0ersus nurse care +anage+ent> a rando+i;ed trial. Ann Intern ed ()%)O%H!>H)F8H%H Deisler . Di**erent +odels to +obili;e .eer su..ort to i+.ro0e diabetes sel*/ +anage+ent and clinical outco+es> e0idence, logistics, e0aluation consid/ erations and needs *or *uture researc,. 6a+ #ract ()%)O(F7Su..l. %9>i(!8 i!( Long &A, &a,nle EC, Ric,ardson D , Loe4enstein C, Vol.. QC. #eer +entoring and 5nancial incenti0es to i+.ro0e glucose control in A*rican A+erican 0eterans> a rando+i;ed trial. Ann Intern ed ()%(O%H">:%"8:(: Tang TS, 6unnell , Cillard , $4an14o R, Deisler . T,e de0elo.+ent o* a .ilot training .rogra+ *or .eer leaders in diabetes> .rocess and content. Diabetes Educ ()%%O!F>"F8FF Tang T, A3ala CU, C,errington A, Rana C. A re0ie4 o* 0olunteer/based .eer su..ort inter0entions in diabetes. Di/ abetes S.ectru+ ()%%O(:>EH8BE Tang TS, $4an14o R, K,iten ', One3 C. Training .eers to deli0er a c,urc,/ based diabetes .re0ention .rogra+. Di/ abetes Educ ()%(O!E>H%B8H(H Dale &R, Killia+s S , Bo43er V. K,at is t,e e**ect o* .eer su..ort on diabetes outco+es in adults^ A s3ste+atic re0ie4. Diabet ed ()%(O(B>%!"%8%!FF 6oster C, Ta3lor S&, Eldridge SE, Ra+sa3 &, Cri*5t,s C&. Sel*/+anage+ent educa/ tion .rogra++es b3 la3 leaders *or .eo.le 4it, c,ronic conditions. Co/ c,rane Database S3st Re0 ())FO7:9> CD))H%)E $orris SL, C,o4d,ur3 6 , Van Le Q, et al. E**ecti0eness o* co++unit3 ,ealt, 4or1ers in t,e care o* .ersons 4it, di/ abetes. Diabet ed ())"O(!>H::8HH" &o,nson T , urra3 R, Duang '. As/ sociations bet4een sel*/+anage+ent education and co+.re,ensi0e diabetes clinical care. Diabetes S.ectru+ ()%)O

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0alue o* diabetes education. Diabetes Educ ())BO!H>FH(8F") Duncan I, A,+ed T, Li PE, et al. As/ sessing t,e 0alue o* t,e diabetes educa/ tor. Diabetes Educ ()%%O!F>"!E8"HF Qra+er Q, cKillia+s &R, C,en D', Si+inerio L . A co++unit3/based di/ abetes .re0ention .rogra+> e0aluation o* t,e grou. li*est3le balance .rogra+ deli0ered b3 diabetes educators. Di/ abetes Educ ()%%O!F>"HB8""E Boul] $C, Daddad E, Qenn3 C#, Kells CA, Sigal R&. E**ects o* e2ercise on gl3/ ce+ic control and bod3 +ass in t3.e ( diabetes +ellitus> a +eta/anal3sis o* controlled clinical trials. &A A ())%O (E">%(%E8%((F Boul] $C, Qenn3 C#, Daddad E, Kells CA, Sigal R&. eta/anal3sis o* t,e e**ect o* structured e2ercise training on cardio/ res.irator3 5tness in T3.e ( diabetes +el/ litus. Diabetologia ())!O:">%)F%8%)E% Colberg SR, Sigal R&, 6ern,all B, et al. E2ercise and t3.e ( diabetes. T,e A+erican College o* S.orts edicine and t,e A+erican Diabetes Association> joint .osition state+ent. Diabetes Care ()%)O!!>("B(8("B" U.S. De.art+ent o* Dealt, and Du+an Ser0ices. ())E #,3sical Acti0it3 Cuide/ lines *or A+ericans Larticle onlineM, ())E. A0ailable *ro+ ,tt.>@@444.,ealt,. go0@.aguidelines@guidelines@de*ault. as.2. Accessed October ()%( Cau;a E, Danusc,/Enserer U, Strasser B, et al. T,e relati0e bene5ts o* endurance and strengt, training on t,e +etabolic *actors and +uscle *unction o* .eo.le 4it, t3.e ( diabetes +ellitus. Arc, #,3s ed Re,abil ())HOE">%H(F8%H!! Dunstan DK, Dal3 R , O4en $, et al. Dig,/intensit3 resistance training i+/ .ro0es gl3ce+ic control in older .atients 4it, t3.e ( diabetes. Diabetes Care ())(O(H>%F(B8%F!" Castaneda C, La3ne &E, uno;/Orians L, et al. A rando+i;ed controlled trial o* resistance e2ercise training to i+.ro0e gl3ce+ic control in older adults 4it, t3.e ( diabetes. Diabetes Care ())(O(H> (!!H8(!:% Sigal R&, Qenn3 C#, Kasser+an DD, Castaneda/Sce..a C. #,3sical acti0it3@ e2ercise and t3.e ( diabetes. Diabetes Care ()):O(F>(H%E8(H!B C,urc, TS, Blair S$, Cocre,a+ S, et al. E**ects o* aerobic and resistance training on ,e+oglobin A%c le0els in .atients 4it, t3.e ( diabetes> a rando+i;ed controlled trial. &A A ()%)O!):>((H!8 (("( Ba2 &&, 'oung LD, 6r3e RL, Bono4 RO, Steinberg DO, Barrett E&. Screening *or coronar3 arter3 disease in .atients 4it, diabetes. Diabetes Care ())FO!)>(F(B8 (F!" Berger , Berc,told #, Cu_..ers D&, et al. etabolic and ,or+onal e**ects o*

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+uscular e2ercise in ju0enile t3.e dia/ betics. Diabetologia %BFFO%!>!HH8!"H Aiello L#, Kong &, Ca0allerano &, Bursell SE, Aiello L . Retino.at,3. In Dandboo1 o* E2ercise in Diabetes. (nd ed. Ruder+an $, De0lin &T, Qris1a A, Eds. Ale2andria, VA, A+erican Diabetes Association, ())(, .. :)%8:%! Le+aster &K, Reiber CE, S+it, DC, Deagert3 #&, Kallace C. Dail3 4eig,t/ bearing acti0it3 does not increase t,e ris1 o* diabetic *oot ulcers. ed Sci S.orts E2erc ())!O!H>%)B!8%)BB Vini1 A, Erbas T. $euro.at,3. In Dandboo1 o* E2ercise in Diabetes. (nd ed. Ruder+an $, De0lin &T, Qris1a A, Eds. Ale2andria, VA, A+erican Diabetes As/ sociation, ())(, .. :"!8:B" Kac1ers 6&, 'oung LD, In;ucc,i SE, et al.O Detection o* Isc,e+ia in As3+./ to+atic Diabetics In0estigators. De/ tection o* silent +3ocardial isc,e+ia in as3+.to+atic diabetic subjects> t,e DIAD stud3. Diabetes Care ()):O(F> %BH:8%B"% Valensi #, Sac,s R$, Dar*ouc,e B, et al. #redicti0e 0alue o* cardiac autono+ic neuro.at,3 in diabetic .atients 4it, or 4it,out silent +3ocardial isc,e+ia. Di/ abetes Care ())%O(:>!!B8!:! ogensen CE. $e.,ro.at,3. In Dand/ boo1 o* E2ercise in Diabetes. (nd ed. Ruder+an $, De0lin &T, Qris1a A, Eds. Ale2andria, VA, A+erican Diabetes As/ sociation, ())(, .. :!!8::B Anderson R&, Crigsb3 AB, 6reedland QE, et al. An2iet3 and .oor gl3ce+ic control> a +eta/anal3tic re0ie4 o* t,e literature. Int & #s3c,iatr3 ed ())(O!(>(!H8(:F Dela,ant3 L , Crant RK, Kittenberg E, et al. Association o* diabetes/related e+otional distress 4it, diabetes treat/ +ent in .ri+ar3 care .atients 4it, T3.e ( diabetes. Diabet ed ())FO(:>:E8H: A+erican Diabetes Association. #s3c,o/ social *actors a**ecting ad,erence, -ualit3 o* li*e, and 4ell/being> ,el.ing .atients co.e. In edical anage+ent o* T3.e % Diabetes. H ed. Qau*+an 6R, Ed. Ale2/ andria, VA, A+erican Diabetes Associa/ tion, ())E, .. %F!8%B! Anderson R&, 6reedland QE, Clouse RE, Lust+an #&. T,e .re0alence o* co+orbid de.ression in adults 4it, diabetes> a +eta/anal3sis. Diabetes Care ())%O(:> %)"B8%)FE Dar1ness E, acdonald K, Valderas &, Co0entr3 #, Cas1 L, Bo4er #. Identi*3ing .s3c,osocial inter0entions t,at i+.ro0e bot, .,3sical and +ental ,ealt, in .a/ tients 4it, diabetes> a s3ste+atic re0ie4 and +eta/anal3sis. Diabetes Care ()%)O !!>B("8B!) Sc,errer &6, Car5eld LD, C,rusciel T, et al. Increased ris1 o* +3ocardial in/ *arction in de.ressed .atients 4it, t3.e ( diabetes. Diabetes Care

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(%). Bot , #ou4er 6, Vuiders+a , 0an elle &#, de &onge #. Association o* co/ e2isting diabetes and de.ression 4it, +ortalit3 a*ter +3ocardial in*arction. Diabetes Care ()%(O!H>H)!8H)B (%%. Sulli0an D, O<Connor #, 6eene3 #, et al. De.ression .redicts all/cause +or/ talit3> e.ide+iological e0aluation *ro+ t,e ACCORD DRPL substud3. Diabetes Care ()%(O!H>%F)E8%F%H (%(. 6is,er L, S1a** , ullan &T, et al. Clinical de.ression 0ersus distress a+ong .atients 4it, t3.e ( diabetes> not just a -uestion o* se+antics. Diabetes Care ())FO!)>H:(8H:E (%!. 6is,er L, Clasgo4 RE, Str3c1er LA. T,e relations,i. bet4een diabetes distress and clinical de.ression 4it, gl3ce+ic control a+ong .atients 4it, t3.e ( di/ abetes. Diabetes Care ()%)O!!>%)!:8 %)!" (%:. Car3 TL, Sa**ord , Cer;o** RB, et al. #erce.tion o* neig,bor,ood .roble+s, ,ealt, be,a0iors, and diabetes outco+es a+ong adults 4it, diabetes in +anaged care> t,e Translating Researc, Into Ac/ tion *or Diabetes 7TRIAD9 stud3. Di/ abetes Care ())EO!%>(F!8(FE (%H. Qaton K, 6an ', Unu_t;er &, Ta3lor &, #incus D, Sc,oenbau+ . De.ression and diabetes> a .otentiall3 let,al co+/ bination. & Cen Intern ed ())EO(!> %HF%8%HFH (%". V,ang U, $orris SL, Cregg EK, C,eng '&, Bec1les C, Qa,n DS. De.ressi0e s3+.to+s and +ortalit3 a+ong .ersons 4it, and 4it,out diabetes. A+ & E.i/ de+iol ())HO%"%>"H(8"") (%F. Rubin RR, #e3rot . #s3c,ological is/ sues and treat+ents *or .eo.le 4it, di/ abetes. & Clin #s3c,ol ())%OHF>:HF8:FE (%E. 'oung/D3+an DL, Da0is CL. Disor/ dered eating be,a0ior in indi0iduals 4it, diabetes> i+.ortance o* conte2t, e0alua/ tion, and classi5cation. Diabetes Care ()%)O!!>"E!8"EB (%B. Be0erl3 EA, Dultgren BA, Broo1s Q , Rit,ol; D, Abra,a+son &, Keinger Q. Understanding .,3sicians< c,allenges 4,en treating t3.e ( diabetic .atients< social and e+otional di*5culties> a -uali/ tati0e stud3. Diabetes Care ()%%O!:> %)E"8%)EE ((). Qaton K&, Lin ED, Von Qor** , et al. Collaborati0e care *or .atients 4it, de/ .ression and c,ronic illnesses. $ Engl & ed ()%)O!"!>("%%8("() ((%. Ciec,ano4s1i #. An integrated +odel *or understanding t,e e2.erience o* in/ di0iduals 4it, co/occuring diabetes and de.ression. Clin Diabetes ()%%O(B> :!8H) (((. Qitabc,i AE, U+.ierre; CE, iles & ,

6is,er &$. D3.ergl3ce+ic crises in adult .atients 4it, diabetes. Diabetes Care ())BO!(>%!!H8 %!:! ((!. Cr3er #E. D3.ogl3cae+ia> t,e li+iting *actor in t,e gl3cae+ic +anage+ent o*

T3.e I and T3.e II diabetes. Diabetologia ())(O:H>B!F8B:E ((:. K,it+er RA, Qarter A&, 'a**e Q, Puesenberr3 C# &r, Selb3 &V. D3.ogl3/ ce+ic e.isodes and ris1 o* de+entia in older .atients 4it, t3.e ( diabetes +el/ litus. &A A ())BO!)%>%H"H8%HF( ((H. #unt,a1ee V, iller E, Launer L&, et al.O ACCORD Crou. o* In0estigatorsO ACCORD/ I$D In0estigators. #oor cogniti0e *unction and ris1 o* se0ere ,3.ogl3ce+ia in t3.e ( diabetes> .ost ,oc e.ide+iologic anal3sis o* t,e ACCORD trial. Diabetes Care ()%(O!H> FEF8FB! ((". &acobson A , usen C, R3an C , et al.O Diabetes Control and Co+.lications Trial@E.ide+iolog3 o* Diabetes Inter/ 0entions and Co+.lications Stud3 Researc, Crou.. Long/ter+ e**ect o* di/ abetes and its treat+ent on cogniti0e *unction. $ Engl & ed ())FO!H">%E:(8 %EH( ((F. Voungas S, #atel A, C,al+ers &, et al.O ADVA$CE Collaborati0e Crou.. Se0ere ,3.ogl3ce+ia and ris1s o* 0ascular e0ents and deat,. $ Engl & ed ()%)O !"!>%:%)8%:%E ((E. cCo3 RC, Van Douten DQ, Viegen*uss &', S,a, $D, Ker+ers RA, S+it, SA. Increased +ortalit3 o* .atients 4it, di/ abetes re.orting se0ere ,3.ogl3ce+ia. Diabetes Care ()%(O!H>%EBF8%B)% ((B. Cr3er #E. Di0erse causes o* ,3.ogl3ce+ia/ associated autono+ic *ailure in diabetes. $ Engl & ed ()):O!H)>((F(8((FB (!). Sc,auer #R, Qas,3a. SR, Kols1i Q, et al. Bariatric surger3 0ersus intensi0e +edi/ cal t,era.3 in obese .atients 4it, diabetes. $ Engl & ed ()%(O!"">%H"F8%HF" (!%. ingrone C, #anun;i S, De Caetano A, et al. Bariatric surger3 0ersus con0en/ tional +edical t,era.3 *or t3.e ( diabetes. $ Engl & ed ()%(O!"">%HFF8%HEH (!(. Dor+an RB, Serrot 6&, iller C&, et al. Case/+atc,ed outco+es in bariatric surger3 *or treat+ent o* t3.e ( diabetes in t,e +orbidl3 obese .atient. Ann Surg ()%(O(HH>(EF8(B! (!!. Buc,4ald D, Esto1 R, 6a,rbac, Q, et al. Keig,t and t3.e ( diabetes a*ter bariatric surger3> s3ste+atic re0ie4 and +eta/ anal3sis. A+ & ed ())BO%((>(:E8(H", eH (!:. Di2on &B, O<Brien #E, #la3*air &, et al. Adjustable gastric banding and con0en/ tional t,era.3 *or t3.e ( diabetes> a ran/ do+i;ed controlled trial. &A A ())EO (BB>!%"8!(! (!H. Co,en RV, #in,eiro &C, Sc,ia0on CA, Salles &E, Kajc,enberg BL, Cu++ings DE. E**ects o* gastric b3.ass surger3 in .atients 4it, t3.e ( diabetes and onl3 +ild obesit3. Diabetes Care ()%(O!H> %:()8%:(E (!". Buc,4ald D, Esto1 R, 6a,rbac, Q, Banel D, Sledge I. Trends in +ortalit3 in bari/ atric surger3> a s3ste+atic re0ie4 and

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+eta/anal3sis. Surger3 ())FO%:(>"(%8 "!(O discussion "!(8"!H Sj[str[+ L, $arbro Q, Sj[str[+ CD, et al.O S4edis, Obese Subjects Stud3. E**ects o* bariatric surger3 on +ortalit3 in S4edis, obese subjects. $ Engl & ed ())FO!HF>F:%8FH( Doerger T&, V,ang #, Segel &E, Qa,n DS, Bar1er LE, Cou.er S. Cost/e**ecti0eness o* bariatric surger3 *or se0erel3 obese adults 4it, diabetes. Diabetes Care ()%)O!!>%B!!8%B!B a1ar3 A, Clar1 & , S,ore AD, et al. edication utili;ation and annual ,ealt, care costs in .atients 4it, t3.e ( diabetes +ellitus be*ore and a*ter bariatric sur/ ger3. Arc, Surg ()%)O%:H>F("8F!% Qeating CL, Di2on &B, oodie L, #eeters A, #la3*air &, O<Brien #E. Cost/ e*5cac3 o* surgicall3 induced 4eig,t loss *or t,e +anage+ent o* t3.e ( diabetes> a rando+i;ed controlled trial. Diabetes Care ())BO!(>HE)8HE: acieje4s1i L, Li0ingston ED, S+it, VA, et al. Sur0i0al a+ong ,ig,/ris1 .a/ tients a*ter bariatric surger3. &A A ()%%O !)H>(:%B8(:(" Di+.ens &, Cadi`re CB, Ba;i , Vouc,e , Cadi`re B, Da.ri C. Long/ter+ out/ co+es o* la.arosco.ic adjustable gastric banding. Arc, Surg ()%%O%:">E)(8E)F S+it, SA, #oland CA. Use o* inAuen;a and .neu+ococcal 0accines in .eo.le 4it, diabetes. Diabetes Care ()))O(!> BH8%)E Col-u,oun A&, $ic,olson QC, Bot,a &L, Ra3+ond $T. E**ecti0eness o* inAuen;a 0accine in reducing ,os.ital ad+issions in .eo.le 4it, diabetes. E.ide+iol In*ect %BBFO%%B>!!H8!:% Bridges CB, 6u1uda Q, U3e1i T , Co2 $&, Singleton &AO Centers *or Disease Control and #re0ention, Ad0isor3 Co++ittee on I++uni;ation #ractices. #re0ention and control o* inAuen;a. Reco++endations o* t,e Ad0isor3 Co++ittee on I++uni;ation #ractices 7ACI#9. KR Reco++ Re. ())(OH% 7RR/!9>%8!% Centers *or Disease Control and #re/ 0ention. Use o* ,e.atitis B 0accination *or adults 4it, diabetes +ellitus> rec/ o++endations o* t,e Ad0isor3 Co+/ +ittee on I++uni;ation #ractices 7ACI#9. KR ()%(O")>%F)B8%F%% Buse &B, Cinsberg D$, Ba1ris CL, et al.O A+erican Deart AssociationO A+erican Diabetes Association. #ri+ar3 .re/ 0ention o* cardio0ascular diseases in .eo.le 4it, diabetes +ellitus> a scienti5c state+ent *ro+ t,e A+erican Deart As/ sociation and t,e A+erican Diabetes Association. Diabetes Care ())FO!)> %"(8%F( Caede #, Lund/Andersen D, #ar0ing DD, #edersen O. E**ect o* a +ulti*acto/ rial inter0ention on +ortalit3 in t3.e (

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diabetes. $ Engl & ed ())EO!HE>HE)8 HB% 6ord ES. Trends in t,e ris1 *or coronar3 ,eart disease a+ong adults 4it, di/ agnosed diabetes in t,e U.S.> 5ndings *ro+ t,e $ational Dealt, and $utrition E2a+ination Sur0e3, %BBB/())E. Di/ abetes Care ()%%O!:>%!!F8%!:! Bobrie C, Cen`s $, Vaur L, et al. Is =isolated ,o+e? ,3.ertension as o./ .osed to =isolated o*5ce? ,3.ertension a sign o* greater cardio0ascular ris1^ Arc, Intern ed ())%O%"%>(()H8((%% Sega R, 6acc,etti R, Bo+belli , et al. #rognostic 0alue o* a+bulator3 and ,o+e blood .ressures co+.ared 4it, o*5ce blood .ressure in t,e general .o.ulation> *ollo4/u. results *ro+ t,e #ressioni Arteriose onitorate e Loro Associa;ioni 7#A ELA9 stud3. Circula/ tion ())HO%%%>%FFF8%FE! C,obanian AV, Ba1ris CL, Blac1 DR, et al.O $ational Deart, Lung, and Blood Institute &oint $ational Co++ittee on #re0ention, Detection, E0aluation, and Treat+ent o* Dig, Blood #ressureO $a/ tional Dig, Blood #ressure Education #rogra+ Coordinating Co++ittee. T,e Se0ent, Re.ort o* t,e &oint $ational Co++ittee on #re0ention, Detection, E0aluation, and Treat+ent o* Dig, Blood #ressure> t,e &$C F re.ort. &A A ())!O(EB>(H")8(HF( Le4ington S, Clar1e R, Pi;ilbas, $, #eto R, Collins RO #ros.ecti0e Studies Col/ laboration. Age/s.eci5c rele0ance o* usual blood .ressure to 0ascular +or/ talit3> a +eta/anal3sis o* indi0idual data *or one +illion adults in "% .ro/ s.ecti0e studies. Lancet ())(O!")> %B)!8%B%! Sta+ler &, Vaccaro O, $eaton &D, Kent4ort, D. Diabetes, ot,er ris1 *ac/ tors, and %(/3r cardio0ascular +ortalit3 *or +en screened in t,e ulti.le Ris1 6actor Inter0ention Trial. Diabetes Care %BB!O%">:!:8::: UQ #ros.ecti0e Diabetes Stud3 Crou.. Tig,t blood .ressure control and ris1 o* +acro0ascular and +icro0ascular co+/ .lications in t3.e ( diabetes> UQ#DS !E. B & %BBEO!%F>F)!8F%! Dansson L, Vanc,etti A, Carrut,ers SC, et al.O DOT Stud3 Crou.. E**ects o* in/ tensi0e blood/.ressure lo4ering and lo4/dose as.irin in .atients 4it, ,3/ .ertension> .rinci.al results o* t,e D3/ .ertension O.ti+al Treat+ent 7DOT9 rando+ised trial. Lancet %BBEO!H%> %FHH8%F"( Adler AI, Stratton I , $eil DA, et al. Association o* s3stolic blood .ressure 4it, +acro0ascular and +icro0ascular co+.lications o* t3.e ( diabetes 7UQ#DS !"9> .ros.ecti0e obser0ational stud3. B & ()))O!(%>:%(8:%B Cus,+an KC, E0ans CK, B3ington R#, et al.O ACCORD Stud3 Crou.. E**ects

o* intensi0e blood/.ressure control in t3.e ( diabetes +ellitus. $ Engl & ed ()%)O!"(>%HFH8%HEH (HB. #atel A, ac a,on S, C,al+ers &, et al.O ADVA$CE Collaborati0e Crou.. E**ects o* a 52ed co+bination o* .erindo.ril and inda.a+ide on +acro0ascular and +icro0ascular outco+es in .atients 4it, t3.e ( diabetes +ellitus 7t,e ADVA$CE trial9> a rando+ised controlled trial. Lancet ())FO!F)>E(B8E:) ("). Coo.er/DeDo** R , Cong ', Dandberg E , et al. Tig,t blood .ressure control and cardio0ascular outco+es a+ong ,3.ertensi0e .atients 4it, diabetes and coronar3 arter3 disease. &A A ()%)O !):>"%8"E ("%. Sleig,t #, Redon &, Verdecc,ia #, et al.O O$TARCET in0estigators. #rognostic 0alue o* blood .ressure in .atients 4it, ,ig, 0ascular ris1 in t,e Ongoing Tel/ +isartan Alone and in co+bination 4it, Ra+i.ril Clobal End.oint Trial stud3. & D3.ertens ())BO(F>%!")8%!"B ("(. cBrien Q, Rabi D , Ca+.bell $, et al. Intensi0e and standard blood .ressure targets in .atients 4it, t3.e ( diabetes +ellitus> s3ste+atic re0ie4 and +eta/ anal3sis. Arc, Intern ed ()%(O%F(> %(B"8%!)! ("!. Bangalore S, Qu+ar S, Lobac, I, esserli 6D. Blood .ressure targets in subjects 4it, t3.e ( diabetes +ellitus@i+.aired *asting glucose> obser0ations *ro+ tra/ ditional and ba3esian rando+/e**ects +eta/anal3ses o* rando+i;ed trials. Cir/ culation ()%%O%(!>(FBB8(E%) (":. Sac1s 6 , S0et1e3 L#, Voll+er K , et al.O DASD/Sodiu+ Collaborati0e Re/ searc, Crou.. E**ects on blood .ressure o* reduced dietar3 sodiu+ and t,e Di/ etar3 A..roac,es to Sto. D3.ertension 7DASD9 diet. $ Engl & ed ())%O!::> !8%) ("H. Tatti #, #a,or , B3ington R#, et al. Outco+e results o* t,e 6osino.ril Versus A+lodi.ine Cardio0ascular E0ents Rando+i;ed Trial 76ACET9 in .atients 4it, ,3.ertension and $IDD . Diabetes Care %BBEO(%>HBF8")! ("". Estacio RO, &e**ers BK, Diatt KR, Biggersta** SL, Ci**ord $, Sc,rier RK. T,e e**ect o* nisoldi.ine as co+.ared 4it, enala.ril on cardio0ascular out/ co+es in .atients 4it, non/insulin/de/ .endent diabetes and ,3.ertension. $ Engl & ed %BBEO!!E>":H8"H( ("F. Sc,rier RK, Estacio RO, e,ler #S, Diatt KR. A..ro.riate blood .ressure control in ,3.ertensi0e and nor+oten/ si0e t3.e ( diabetes +ellitus> a su++ar3 o* t,e ABCD trial. $at Clin #ract $e.,rol ())FO!>:(E8:!E ("E. ALLDAT O*5cers and Coordinators *or t,e ALLDAT Collaborati0e Researc, Crou.. T,e Anti,3.ertensi0e and Li.id/Lo4ering Treat+ent to #re0ent

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,ig,/ris1 ,3.ertensi0e .atients ran/ do+i;ed to angiotensin/con0erting en/ ;3+e in,ibitor or calciu+ c,annel bloc1er 0s diuretic> T,e Anti,3.erten/ si0e and Li.id/Lo4ering Treat+ent to #re0ent Deart Attac1 Trial 7ALLDAT9. &A A ())(O(EE>(BE%8(BBF #sat3 B , S+it, $L, Sisco0ic1 DS, et al. Dealt, outco+es associated 4it, anti/ ,3.ertensi0e t,era.ies used as 5rst/line agents. A s3ste+atic re0ie4 and +eta/ anal3sis. &A A %BBFO(FF>F!B8F:H Deart Outco+es #re0ention E0aluation Stud3 In0estigators. E**ects o* ra+i.ril on cardio0ascular and +icro0ascular outco+es in .eo.le 4it, diabetes +el/ litus> results o* t,e DO#E stud3 and ICRO/DO#E substud3. Lancet ()))O !HH>(H!8(HB c urra3 &&, Ostergren &, S4edberg Q, et al.O CDAR In0estigators and Co+/ +ittees. E**ects o* candesartan in .a/ tients 4it, c,ronic ,eart *ailure and reduced le*t/0entricular s3stolic *unction ta1ing angiotensin/con0erting/en;3+e in,ibitors> t,e CDAR /Added trial. Lancet ())!O!"(>F"F8FF% #*e**er A, S4edberg Q, Cranger CB, et al.O CDAR In0estigators and Co+/ +ittees. E**ects o* candesartan on +or/ talit3 and +orbidit3 in .atients 4it, c,ronic ,eart *ailure> t,e CDAR / O0erall .rogra++e. Lancet ())!O!"(> FHB8F"" Cranger CB, c urra3 &&, 'usu* S, et al.O CDAR In0estigators and Co++ittees. E**ects o* candesartan in .atients 4it, c,ronic ,eart *ailure and reduced le*t/ 0entricular s3stolic *unction intolerant to angiotensin/con0erting/en;3+e in/ ,ibitors> t,e CDAR /Alternati0e trial. Lancet ())!O!"(>FF(8FF" Lind,ol+ LD, Ibsen D, Da,l[* B, et al.O LI6E Stud3 Crou.. Cardio0ascular +orbidit3 and +ortalit3 in .atients 4it, diabetes in t,e Losartan Inter0ention 6or End.oint reduction in ,3.ertension stud3 7LI6E9> a rando+ised trial against atenolol. Lancet ())(O!HB>%)):8%)%) Berl T, Dunsic1er LC, Le4is &B, et al.O Irbesartan Diabetic $e.,ro.at,3 Trial. Collaborati0e Stud3 Crou.. Cardio0as/ cular outco+es in t,e Irbesartan Di/ abetic $e.,ro.at,3 Trial o* .atients 4it, t3.e ( diabetes and o0ert ne.,ro.at,3. Ann Intern ed ())!O%!E>H:(8H:B c anus R&, ant &, Bra3 E#, et al. Tele+onitoring and sel*/+anage+ent in t,e control o* ,3.ertension 7TAS I$D(9> a rando+ised controlled trial. Lancet ()%)O !F">%"!8%F( Der+ida RC, A3ala DE, ojXn A, 6ern ande; &R. InAuence o* ti+e o* da3 o* blood .ressure/lo4ering treat+ent on cardio0ascular ris1 in ,3.ertensi0e .a/ tients 4it, t3.e ( diabetes. Diabetes Care ()%%O!:>%(F)8%(F"

(FE. Sibai B . Treat+ent o* ,3.ertension in .regnant 4o+en. $ Engl & ed %BB"O !!H>(HF8("H (FB. Baigent C, Qeec, A, Qearne3 # , et al.O C,olesterol Treat+ent Trialists< 7CTT9 Collaborators. E*5cac3 and sa*et3 o* c,o/ lesterol/lo4ering treat+ent> .ros.ecti0e +eta/anal3sis o* data *ro+ B),)H" .artic/ i.ants in %: rando+ised trials o* statins. Lancet ())HO!"">%("F8%(FE (E). i,a3lo0a B, E+berson &, Blac14ell L, et al.O C,olesterol Treat+ent Trialists< 7CTT9 Collaborators. T,e e**ects o* lo4ering LDL c,olesterol 4it, statin t,era.3 in .eo.le at lo4 ris1 o* 0ascular disease> +eta/anal3sis o* indi0idual data *ro+ (F rando+ised trials. Lancet ()%(O !E)>HE%8HB) (E%. #3orala Q, #edersen TR, Qje1s,us &, 6aerge+an O, Olsson AC, T,orgeirsson C. C,olesterol lo4ering 4it, si+0astatin i+.ro0es .rognosis o* diabetic .atients 4it, coronar3 ,eart disease. A subgrou. anal3sis o* t,e Scandina0ian Si+0astatin Sur0i0al Stud3 7:S9. Diabetes Care %BBFO ()>"%:8"() (E(. Collins R, Ar+itage &, #aris, S, Sleig, #, #eto RO Deart #rotection Stud3 Collabo/ rati0e Crou.. RC@BD6 Deart #rotection Stud3 o* c,olesterol/lo4ering 4it, si+/ 0astatin in HB"! .eo.le 4it, diabetes> a rando+ised .lacebo/ controlled trial. Lancet ())!O!"%>())H8 ()%" (E!. Coldberg RB, ellies &, Sac1s 6 , et al.O t,e Care In0estigators. Cardio0as/ cular e0ents and t,eir reduction 4it, .ra0astatin in diabetic and glucose/in/ tolerant +3ocardial in*arction sur0i0ors 4it, a0erage c,olesterol le0els> sub/ grou. anal3ses in t,e c,olesterol and recurrent e0ents 7CARE9 trial. Circula/ tion %BBEOBE>(H%!8(H%B (E:. S,e.,erd &, Barter #, Car+ena R, et al. E**ect o* lo4ering LDL c,olesterol sub/ stantiall3 belo4 currentl3 reco++ended le0els in .atients 4it, coronar3 ,eart disease and diabetes> t,e Treating to $e4 Targets 7T$T9 stud3. Diabetes Care ())"O(B>%(()8%((" (EH. Se0er #S, #oulter $R, Da,l[* B, et al. Reduction in cardio0ascular e0ents 4it, ator0astatin in (,H!( .atients 4it, t3.e ( diabetes> Anglo/Scandina0ian Cardiac Outco+es Trialdli.id/lo4ering ar+ 7ASCOT/LLA9. Diabetes Care ())HO(E> %%H%8%%HF (E". Qno.. RD, d<E+den , S+ilde &C, #ococ1 S&. E*5cac3 and sa*et3 o* ator/ 0astatin in t,e .re0ention o* cardio0as/ cular end .oints in subjects 4it, t3.e ( diabetes> t,e Ator0astatin Stud3 *or #re/

0ention o* Coronar3 Deart Disease End.oints in non/insulin/de.endent diabetes +ellitus 7AS#E$9. Diabetes Care ())"O(B>%:FE8 %:EH (EF. Col,oun D , Betteridge D&, Durrington #$, et al.O CARDS in0estigators. #ri+ar3 .re0ention o* cardio0ascular disease

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4it, ator0astatin in t3.e ( diabetes in t,e Collaborati0e Ator0astatin Diabetes Stud3 7CARDS9> +ulticentre rando/ +ised .lacebo/controlled trial. Lancet ()):O!":>"EH8"B" Qearne3 # , Blac14ell L, Collins R, et al.O C,olesterol Treat+ent Trialists< 7CTT9 Collaborators. E*5cac3 o* c,oles/ terol/lo4ering t,era.3 in %E,"E" .eo.le 4it, diabetes in %: rando+ised trials o* statins> a +eta/anal3sis. Lancet ())EO !F%>%%F8%(H Raj.at,a1 S$, Qu+b,ani D&, Crandall &, Bar;ilai $, Alder+an , Rid1er # . Statin t,era.3 and ris1 o* de0elo.ing t3.e ( diabetes> a +eta/anal3sis. Diabetes Care ())BO!(>%B(:8%B(B Sattar $, #reiss D, urra3 D , et al. Statins and ris1 o* incident diabetes> a collaborati0e +eta/anal3sis o* rando/ +ised statin trials. Lancet ()%)O!FH> F!H8F:( Rid1er # , #rad,an A, ac6ad3en &C, Libb3 #, Cl3nn R&. Cardio0ascular ben/ e5ts and diabetes ris1s o* statin t,era.3 in .ri+ar3 .re0ention> an anal3sis *ro+ t,e &U#ITER trial. Lancet ()%(O!E)> H"H8HF% Sing, I , S,is,e,bor D, Ansell B&. Dig,/densit3 li.o.rotein as a t,era.eu/ tic target> a s3ste+atic re0ie4. &A A ())FO(BE>FE"8FBE Canner #L, Berge QC, Kenger $Q, et al. 6i*teen 3ear +ortalit3 in Coronar3 Drug #roject .atients> long/ter+ bene5t 4it, niacin. & A+ Coll Cardiol %BE"OE>%(:H8 %(HH Rubins DB, Robins S&, Collins D, et al.O Veterans A**airs Dig,/Densit3 Li.o.ro/ tein C,olesterol Inter0ention Trial Stud3 Crou.. Ce+5bro;il *or t,e secondar3 .re0ention o* coronar3 ,eart disease in +en 4it, lo4 le0els o* ,ig,/densit3 li/ .o.rotein c,olesterol. $ Engl & ed %BBBO!:%>:%)8:%E 6ric1 D, Elo O, Daa.a Q, et al. Delsin1i Deart Stud3> .ri+ar3/.re0ention trial 4it, ge+5bro;il in +iddle/aged +en 4it, d3sli.ide+ia. Sa*et3 o* treat+ent, c,anges in ris1 *actors, and incidence o* coronar3 ,eart disease. $ Engl & ed %BEFO!%F>%(!F8%(:H Qeec, A, Si+es R&, Barter #, et al.O 6IELD Stud3 In0estigators. E**ects o* long/ter+ *eno5brate t,era.3 on cardio0ascular e0ents in BFBH .eo.le 4it, t3.e ( di/ abetes +ellitus 7t,e 6IELD stud39> rando+ised controlled trial. Lancet ())HO!"">%E:B8%E"% &ones #D, Da0idson D. Re.orting rate o* r,abdo+3ol3sis 4it, *eno5brate % statin 0ersus ge+5bro;il % an3 statin. A+ & Cardiol ())HOBH>%()8%(( Cinsberg D$, Ela+ B, Lo0ato LC, et al.O ACCORD Stud3 Crou.. E**ects o* co+bination li.id t,era.3 in t3.e ( di/ abetes +ellitus. $ Engl & ed ()%)O!"(> %H"!8%HF:

(BB. Boden KE, #robst5eld &L, Anderson T, et al.O AI /DICD In0estigators. $iacin in .atients 4it, lo4 DDL c,olesterol le0els recei0ing intensi0e statin t,e/ ra.3. $ Engl & ed ()%%O!"H>((HH8 (("F !)). E2.ert #anel on Detection, E0aluation, and Treat+ent o* Dig, Blood C,oles/ terol in Adults. E2ecuti0e Su++ar3 o* t,e T,ird Re.ort o* t,e $ational C,o/ lesterol Education #rogra+ 7$CE#9 E2/ .ert #anel on Detection, E0aluation, and Treat+ent o* Dig, Blood C,olesterol in Adults 7Adult Treat+ent #anel III9. &A A ())%O(EH>(:E"8(:BF !)%. Da34ard RA, Do*er T#, Vijan S. $arra/ ti0e re0ie4> lac1 o* e0idence *or reco++ended lo4/densit3 li.o.rotein treat+ent targets> a sol0able .roble+. Ann Intern ed ())"O%:H>H()8H!) !)(. Cannon C#, Braun4ald E, cCabe CD, et al.O #ra0astatin or Ator0astatin E0alua/ tion and In*ection T,era.3/ T,ro+bol3sis in 3ocardial In*arction (( In0estigators. Intensi0e 0ersus +oderate li.id lo4ering 4it, statins a*ter acute coronar3 s3n/ dro+es. $ Engl & ed ()):O!H)> %:BH8%H): !)!. de Le+os &A, Bla;ing A, Ki0iott SD, et al.O A to V In0estigators. Earl3 intensi0e 0s a dela3ed conser0ati0e si+0astatin strateg3 in .atients 4it, acute coronar3 s3ndro+es> .,ase V o* t,e A to V trial. &A A ()):O(B(>%!)F8 %!%" !):. $issen SE, Tu;cu E , Sc,oen,agen #, et al.O REVERSAL In0estigators. E**ect o* intensi0e co+.ared 4it, +oderate li.id/ lo4ering t,era.3 on .rogression o* cor/ onar3 at,erosclerosis> a rando+i;ed controlled trial. &A A ()):O(B%>%)F%8 %)E) !)H. Crund3 S , Clee+an &I, er; C$, et al.O $ational Deart, Lung, and Blood In/ stituteO A+erican College o* Cardiolog3 6oundationO A+erican Deart Associa/ tion. I+.lications o* recent clinical trials *or t,e $ational C,olesterol Education #rogra+ Adult Treat+ent #anel III guidelines. Circulation ()):O%%)>((F8 (!B !)". Brun;ell &D, Da0idson , 6urberg CD, et al.O A+erican Diabetes AssociationO A+erican College o* Cardiolog3 6oun/ dation. Li.o.rotein +anage+ent in .atients 4it, cardio+etabolic ris1> con/ sensus state+ent *ro+ t,e A+erican Diabetes Association and t,e A+erican College o* Cardiolog3 6oundation. Di/ abetes Care ())EO!%>E%%8E(( !)F. C,as+an DI, #osada D, Subra,+an3an L, Coo1 $R, Stanton V# &r, Rid1er # . #,ar+acogenetic stud3 o* statin t,era.3 and c,olesterol reduction. &A A ()):O (B%>(E(%8(E(F

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obser0ational stud3. Curr ed Res O.in ()%(O(E>!F%8!FE Ela+ B, Dunning,a1e DB, Da0is QB, et al. E**ect o* niacin on li.id and li.o/ .rotein le0els and gl3ce+ic control in .atients 4it, diabetes and .eri.,eral arterial disease. T,e AD IT Stud3> a rando+i;ed trial. &A A ()))O(E:> %("!8%(F) Crund3 S , Vega CL, cCo0ern E, et al.O Diabetes ulticenter Researc, Crou.. E*5cac3, sa*et3, and tolerabilit3 o* once/dail3 niacin *or t,e treat+ent o* d3sli.ide+ia associated 4it, t3.e ( di/ abetes> results o* t,e assess+ent o* di/ abetes control and e0aluation o* t,e e*5cac3 o* nias.an trial. Arc, Intern ed ())(O%"(>%H"E8%HF" Baigent C, Blac14ell L, Collins R, et al.O Antit,ro+botic Trialists< 7ATT9 Collab/ oration. As.irin in t,e .ri+ar3 and sec/ ondar3 .re0ention o* 0ascular disease> collaborati0e +eta/anal3sis o* indi0idual .artici.ant data *ro+ rando+ised trials. Lancet ())BO!F!>%E:B8%E") Oga4a D, $a1a3a+a , ori+oto T, et al.O &a.anese #ri+ar3 #re0ention o* At,erosclerosis 4it, As.irin *or Diabetes 7&#AD9 Trial In0estigators. Lo4/dose as.irin *or .ri+ar3 .re0ention o* at,/ erosclerotic e0ents in .atients 4it, t3.e ( diabetes> a rando+i;ed controlled trial. &A A ())EO!))>(%!:8(%:% Belc, &, acCuis, A, Ca+.bell I, et al. T,e .re0ention o* .rogression o* arterial disease and diabetes 7#O#ADAD9 trial> *actorial rando+ised .lacebo controlled trial o* as.irin and antio2idants in .a/ tients 4it, diabetes and as3+.to+atic .eri.,eral arterial disease. B & ())EO !!F>a%E:) #ignone , Earns,a4 S, Tice &A, #letc,er &. As.irin, statins, or bot, drugs *or t,e .ri+ar3 .re0ention o* coronar3 ,eart disease e0ents in +en> a cost/utilit3 anal3sis. Ann Intern ed ())"O%::>!("8!!" #ignone , Alberts &, Col4ell &A, et al.O A+erican Diabetes AssociationO A+eri/ can Deart AssociationO A+erican College o* Cardiolog3 6oundation. As.irin *or .ri+ar3 .re0ention o* cardio0ascular e0ents in .eo.le 4it, diabetes> a .osition state+ent o* t,e A+erican Diabetes Association, a scienti5c state+ent o* t,e A+erican Deart Association, and an e2/ .ert consensus docu+ent o* t,e A+eri/ can College o* Cardiolog3 6oundation. Diabetes Care ()%)O!!>%!BH8%:)( Ca+.bell CL, S+3t, S, ontalescot C, Stein,ubl SR. As.irin dose *or t,e .re/ 0ention o* cardio0ascular disease> a
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bene5t o* clo.idogrel 0ersus as.irin in .atients 4it, diabetes +ellitus. A+ & Cardiol ())(OB)>"(H8"(E Voulgari C, Qatsila+bros $, Tentolouris $. S+o1ing cessation .redicts a+eliora/ tion o* +icroalbu+inuria in ne4l3 di/ agnosed t3.e ( diabetes +ellitus> a %/3ear .ros.ecti0e stud3. etabolis+ ()%%O")> %:H"8%:": Ranne3 L, el0in C, Lu2 L, cClain E, Lo,r Q$. S3ste+atic re0ie4> s+o1ing cessation inter0ention strategies *or adults and adults in s.ecial .o.ulations. Ann Intern ed ())"O%:H>E:H8EH" Scogna+iglio R, $egut C, Ra+ondo A, Tiengo A, A0ogaro A. Detection o* cor/ onar3 arter3 disease in as3+.to+atic .atients 4it, t3.e ( diabetes +ellitus. & A+ Coll Cardiol ())"O:F>"H8F% Boden KE, O<Rour1e RA, Teo QQ, et al.O COURACE Trial Researc, Crou.. O.ti/ +al +edical t,era.3 4it, or 4it,out #CI *or stable coronar3 disease. $ Engl & ed ())FO!H">%H)!8%H%" 6r3e RL, August #, Broo1s , et al.O BARI (D Stud3 Crou.. A rando+i;ed trial o* t,era.ies *or t3.e ( diabetes and coronar3 arter3 disease. $ Engl & ed ())BO!")>(H)!8(H%H Kac1ers 6&, C,3un DA, 'oung LD, et al.O Detection o* Isc,e+ia in As3+.to+atic Diabetics 7DIAD9 In0estigators. Resolu/ tion o* as3+.to+atic +3ocardial isc,e/ +ia in .atients 4it, t3.e ( diabetes in t,e Detection o* Isc,e+ia in As3+./ to+atic Diabetics 7DIAD9 stud3. Di/ abetes Care ())FO!)>(EB(8(EBE 'oung LD, Kac1ers 6&, C,3un DA, et al.O DIAD In0estigators. Cardiac outco+es a*ter screening *or as3+.to+atic coro/ nar3 arter3 disease in .atients 4it, t3.e ( diabetes> t,e DIAD stud3> a rando+i;ed controlled trial. &A A ())BO!)%>%H:F8 %HHH Dada+it;13 , Dein 6, e3er T, et al. #rognostic 0alue o* coronar3 co+.uted to+ogra.,ic angiogra.,3 in diabetic .atients 4it,out 1no4n coronar3 arter3 disease. Diabetes Care ()%)O!!>%!HE8%!"! El1eles RS, Codsland I6, 6e,er D, et al.O #REDICT Stud3 Crou.. Coronar3 calciu+ +easure+ent i+.ro0es .redic/ tion o* cardio0ascular e0ents in as3+./ to+atic .atients 4it, t3.e ( diabetes> t,e #REDICT stud3. Eur Deart & ())EO(B> ((::8((H% C,oi EQ, C,un E&, C,oi SI, et al. As/ sess+ent o* subclinical coronar3 at,/ erosclerosis in as3+.to+atic .atients 4it, t3.e ( diabetes +ellitus 4it, single .,oton e+ission co+.uted to+ogra.,3 and coronar3 co+.uted to+ogra.,3 angiogra.,3. A+ & Cardiol ())BO%):> EB)8EB" Braun4ald E, Do+ans1i &, 6o4ler SE, et al.O #EACE Trial In0estigators. An/ giotensin/con0erting/en;3+e in,ibition

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in stable coronar3 arter3 disease. $ Engl & ed ()):O!H%>()HE8()"E !!). 'usu* S, Teo Q, Anderson C, et al.O Tel/ +isartan Rando+ised Assess+e$t Stud3 in ACE i$tolerant subjects 4it, cardio/ 0ascular Disease 7TRA$SCE$D9 In0es/ tigators. E**ects o* t,e angiotensin/ rece.tor bloc1er tel+isartan on cardio0ascular e0/ ents in ,ig,/ris1 .atients intolerant to an/ giotensin/ con0erting en;3+e in,ibitors> a rando+ised controlled trial. Lancet ())EO !F(>%%F:8%%E! !!%. Carg &#, Ba1ris CL. icroalbu+inuria> +ar1er o* 0ascular d3s*unction, ris1 *a/ ctor *or cardio0ascular disease. Vasc ed ())(OF>!H8:! !!(. Qlausen Q, Borc,/&o,nsen Q, 6eldt/ Ras+ussen B, et al. Ver3 lo4 le0els o* +icroalbu+inuria are associated 4it, increased ris1 o* coronar3 ,eart disease and deat, inde.endentl3 o* renal *unc/ tion, ,3.ertension, and diabetes. Circu/ lation ()):O%%)>!(8!H !!!. Call A, Dougaard #, Borc,/&o,nsen Q, #ar0ing DD. Ris1 *actors *or de0elo/ .+ent o* inci.ient and o0ert diabetic ne.,ro.at,3 in .atients 4it, non/ insulin de.endent diabetes +ellitus> .ros.ecti0e, obser0ational stud3. B & %BBFO!%:> FE!8FEE !!:. Ra0id , Lang R, Rac,+ani R, Lis,ner . Long/ter+ reno.rotecti0e e**ect o* angiotensin/con0erting en;3+e in,ibition in non/insulin/de.endent diabetes +elli/ tus. A F/3ear *ollo4/u. stud3. Arc, Intern ed %BB"O%H">(E"8 (EB !!H. Reic,ard #, $ilsson B', Rosen-0ist U. T,e e**ect o* long/ter+ intensi5ed in/ sulin treat+ent on t,e de0elo.+ent o* +icro0ascular co+.lications o* diabetes +ellitus. $ Engl & ed %BB!O!(B>!):8 !)B !!". T,e Diabetes Control and Co+.lica/ tions 7DCCT9 Researc, Crou.. E**ect o* intensi0e t,era.3 on t,e de0elo.+ent and .rogression o* diabetic ne.,ro.at,3 in t,e Diabetes Control and Co+.lica/ tions Trial. Qidne3 Int %BBHO:F>%F)!8 %F() !!F. Le4is E&, Dunsic1er LC, Bain R#, Ro,de RDO T,e Collaborati0e Stud3 Crou.. T,e e**ect o* angiotensin/con0erting/en;3+e in,ibition on diabetic ne.,ro.at,3. $ Engl & ed %BB!O!(B>%:H"8%:"( !!E. La**el L , cCill &B, Cans D&O $ort, A+erican icroalbu+inuria Stud3 Crou.. T,e bene5cial e**ect o* angio/ tensin/con0erting en;3+e in,ibition 4it, ca.to.ril on diabetic ne.,ro.at,3 in nor+otensi0e IDD .atients 4it, +icroalbu+inuria. A+ & ed %BBHOBB> :BF8H): !!B. Ba1ris CL, Killia+s , D4or1in L, et al.O $ational Qidne3 6oundation D3.erten/ sion and Diabetes E2ecuti0e Co++ittees Kor1ing Crou.. #reser0ing renal *unc/ tion in adults care.diabetesjournals.org

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diabetes> a consensus a..roac,. A+ & Qidne3 Dis ()))O!">":"8""% !:). Re+u;;i C, acia , Ruggenenti #. #re0ention and treat+ent o* diabetic re/ nal disease in t3.e ( diabetes> t,e BE$EDICT stud3. & A+ Soc $e.,rol ())"O%F7Su..l. (9>SB)8 SBF !:%. Daller D, Ito S, I;;o &L &r, et al.O ROAD A# Trial In0estigators. Ol+esartan *or t,e dela3 or .re0ention o* +icroalbu+inuria in t3.e ( diabetes. $ Engl & ed ()%%O!":> B)F8B%F !:(. Bilous R, C,atur0edi $, Sjclie AQ, et al. E**ect o* candesartan on +icroalbu/ +inuria and albu+in e2cretion rate in diabetes> t,ree rando+i;ed trials. Ann Intern ed ())BO%H%>%%8() !:!. auer , Vin+an B, Cardiner R, et al. Renal and retinal e**ects o* enala.ril and losartan in t3.e % diabetes. $ Engl & ed ())BO!"%>:)8H% !::. Le4is E&, Dunsic1er LC, Clar1e KR, et al.O Collaborati0e Stud3 Crou.. Re/ no.rotecti0e e**ect o* t,e angiotensin/ rece.tor antagonist irbesartan in .atients 4it, ne.,ro.at,3 due to t3.e ( diabetes. $ Engl & ed ())%O!:H>EH%8 E") !:H. Brenner B , Coo.er E, de Veeu4 D, et al.O RE$AAL Stud3 In0estigators. E*/ *ects o* losartan on renal and cardio0as/ cular outco+es in .atients 4it, t3.e ( diabetes and ne.,ro.at,3. $ Engl & ed ())%O!:H>E"%8E"B !:". #ar0ing DD, Le,nert D, Br[c,ner/ ortensen &, Co+is R, Andersen S, Arner #O Irbesartan in #atients 4it, T3.e ( Diabetes and icroalbu+inuria Stud3 Crou.. T,e e**ect o* irbesartan on t,e de0elo.+ent o* diabetic ne.,ro.at,3 in .atients 4it, t3.e ( diabetes. $ Engl & ed ())%O!:H>EF)8EFE !:F. #e.ine C&, Dandberg E , Coo.er/ DeDo** R , et al.O I$VEST In0estigators. A calciu+ antagonist 0s a non/calciu+ antagonist ,3.ertension treat+ent stra/ teg3 *or .atients 4it, coronar3 arter3 disease. T,e International Vera.a+il/ Trandola.ril Stud3 7I$VEST9> a ran/ do+i;ed controlled trial. &A A ())!O (B)>(E)H8(E%" !:E. Ba1ris CL, Sio+os , Ric,ardson D, et al.O VAL/Q Stud3 Crou.. ACE in/ ,ibition or angiotensin rece.tor bloc1/ ade> i+.act on .otassiu+ in renal *ailure. Qidne3 Int ()))OHE>()E:8()B( !:B. ogensen CE, $elda+ S, Ti11anen I, et al. Rando+ised controlled trial o* dual bloc1ade o* renin/angiotensin s3ste+ in .atients 4it, ,3.ertension, +icro/ albu+inuria, and non/insulin de.endent diabetes> t,e candesartan

and lisino.ril +icroalbu+inuria 7CAL 9 stud3. B & ()))O!(%>%::)8 %::: !H). Sc,joedt Q&, &acobsen #, Rossing Q, Boo+s+a 6, #ar0ing DD. Dual bloc1ade o* t,e renin/angiotensin/ aldosterone s3ste+ in diabetic ne.,ro.at,3> t,e role

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o* aldosterone. Dor+ etab Res ())HO!F 7Su..l. %9>:8E Sc,joedt Q&, Rossing Q, &u,l TR, et al. Bene5cial i+.act o* s.ironolactone in diabetic ne.,ro.at,3. Qidne3 Int ())HO "E>(E(B8(E!" #ar0ing DD, #ersson 6, Le4is &B, Le4is E&, Dollenberg $QO AVOID Stud3 In/ 0estigators. Alis1iren co+bined 4it, losartan in t3.e ( diabetes and ne/ .,ro.at,3. $ Engl & ed ())EO!HE> (:!!8(::" 'usu* S, Teo QQ, #ogue &, et al.O O$TARCET In0estigators. Tel+isartan, ra+i.ril, or bot, in .atients at ,ig, ris1 *or 0ascular e0ents. $ Engl & ed ())EO !HE>%H:F8%HHB #ijls LT, de Vries D, Don1er A&, 0an Eij1 &T. T,e e**ect o* .rotein restriction on albu+inuria in .atients 4it, t3.e ( di/ abetes +ellitus> a rando+i;ed trial. $e.,rol Dial Trans.lant %BBBO%:>%::H8 %:H! #edrini T, Le0e3 AS, Lau &, C,al+ers TC, Kang #D. T,e e**ect o* dietar3 .rotein restriction on t,e .rogression o* diabetic and nondiabetic renal diseases> a +eta/anal3sis. Ann Intern ed %BB"O %(:>"(F8"!( Dansen D#, Tauber/Lassen E, &ensen BR, #ar0ing DD. E**ect o* dietar3 .rotein restriction on .rognosis in .atients 4it, diabetic ne.,ro.at,3. Qidne3 Int ())(O "(>(()8((E Qasis1e BL, La1atua &D, a &V, Louis TA. A +eta/anal3sis o* t,e e**ects o* dietar3 .rotein restriction on t,e rate o* decline in renal *unction. A+ & Qidne3 Dis %BBEO !%>BH:8B"% E1no3an C, Dostetter T, Ba1ris CL, et al. #roteinuria and ot,er +ar1ers o* c,ronic 1idne3 disease> a .osition state+ent o* t,e $ational Qidne3 6oundation 7$Q69 and t,e $ational Institute o* Diabetes and Digesti0e and Qidne3 Diseases 7$IDDQ9. A+ & Qidne3 Dis ())!O:(> "%F8"(( Le0e3 AS, Cores, &, Bal1 E, et al.O $a/ tional Qidne3 6oundation. $ational Qidne3 6oundation .ractice guidelines *or c,ronic 1idne3 disease> e0aluation, classi5cation, and strati5cation. Ann In/ tern ed ())!O%!B>%!F8%:F Qra+er D, olitc, E. Screening *or 1idne3 disease in adults 4it, diabetes. Diabetes Care ())HO(E>%E%!8%E%" Qra+er D&, $gu3en PD, Cur,an C, Dsu C'. Renal insu*5cienc3 in t,e absence o* albu+inuria and retino.at,3 a+ong adults 4it, t3.e ( diabetes +ellitus. &A A ())!O(EB>!(F!8!(FF Le0e3 AS, Bosc, &#, Le4is &B, Creene T, Rogers $, Rot, DO odi5cation o* Diet in Renal Disease Stud3 Crou.. A +ore accurate +et,od to esti+ate glo+erular 5ltration rate *ro+ seru+ creatinine> a ne4 .rediction e-uation. Ann Intern ed %BBBO%!)>:"%8:F)

!"!. Rigalleau V, Lasseur C, #erle+oine C, et al. Esti+ation o* glo+erular 5ltration rate in diabetic subjects> Coc1cro*t *or/ +ula or odi5cation o* Diet in Renal Disease stud3 e-uation^ Diabetes Care ())HO(E>E!E8E:! !":. Le0ins13 $C. S.ecialist e0aluation in c,ronic 1idne3 disease> too little, too late. Ann Intern ed ())(O%!F>H:(8H:! !"H. Qlein R. D3.ergl3ce+ia and +icro0as/ cular and +acro0ascular disease in di/ abetes. Diabetes Care %BBHO%E>(HE8("E !"". Estacio RO, c6arling E, Biggersta** S, &e**ers BK, &o,nson D, Sc,rier RK. O0ert albu+inuria .redicts diabetic ret/ ino.at,3 in Dis.anics 4it, $IDD . A+ & Qidne3 Dis %BBEO!%>B:F8BH! !"F. Les1e C, Ku S', Dennis A, et al.O Barbados E3e Stud3 Crou.. D3.ergl3/ ce+ia, blood .ressure, and t,e B/3ear incidence o* diabetic retino.at,3> t,e Barbados E3e Studies. O.,t,al+olog3 ())HO%%(>FBB8E)H !"E. 6ong DS, Aiello L#, 6erris 6L !rd, Qlein R. Diabetic retino.at,3. Diabetes Care ()):O(F>(H:)8(HH! !"B. Diabetes Control and Co+.lications Trial Researc, Crou.. E**ect o* .reg/ nanc3 on +icro0ascular co+.lications in t,e Diabetes Control and Co+.lica/ tions Trial. Diabetes Care ()))O(!> %)E:8%)B% !F). T,e Diabetic Retino.at,3 Stud3 Re/ searc, Crou.. #reli+inar3 re.ort on e*/ *ects o* .,otocoagulation t,era.3. A+ & O.,t,al+ol %BF"OE%>!E!8!B" !F%. Earl3 Treat+ent Diabetic Retino.at,3 Stud3 Researc, Crou.. #,otocoagula/ tion *or diabetic +acular ede+a. Earl3 Treat+ent Diabetic Retino.at,3 Stud3 re.ort nu+ber %. Arc, O.,t,al+ol %BEHO%)!>%FB"8%E)" !F(. $gu3en PD, Bro4n D , arcus D , et al.O RISE and RIDE Researc, Crou.. Ranibi;u+ab *or diabetic +acular ede+a> results *ro+ ( .,ase III ran/ do+i;ed trials> RISE and RIDE. O.,/ t,al+olog3 ()%(O%%B>FEB8E)% !F!. #earson #A, Co+stoc1 TL, I. , et al. 6luocinolone acetonide intra0itreal i+/ .lant *or diabetic +acular ede+a> a !/ 3ear +ulticenter, rando+i;ed, controlled clinical trial. O.,t,al+olog3 ()%%O%%E> %HE)8%HEF !F:. C,e4 E', A+brosius KT. U.date o* t,e ACCORD E3e Stud3. $ Engl & ed ()%%O!":>%EE8%EB !FH. Qeec, AC, itc,ell #, Su++anen #A, et al.O 6IELD Stud3 In0estigators. E**ect o* *eno5brate on t,e need *or laser treat+ent *or diabetic retino.at,3 76IELD stud39> a rando+ised controlled trial. Lancet ())FO!F)>%"EF8%"BF !F". Agard, E, Tababat/Q,ani #. Ado.ting !/3ear screening inter0als *or sig,t/ t,reatening retinal 0ascular lesions in t3.e ( diabetic subjects 4it,out

retino.at,3. Diabetes Care ()%%O!:> %!%E8%!%B !FF. 6ong DS, Aiello L, Cardner TK, et al.O A+erican Diabetes Association. Reti/ no.at,3 in diabetes. Diabetes Care ()):O (F7Su..l. %9>SE:8 SEF !FE. A,+ed &, Kard T#, Bursell SE, Aiello L , Ca0allerano &D, Vigers13 RA. T,e sensiti0it3 and s.eci5cit3 o* non+3/ driatic digital stereosco.ic retinal i+ag/ ing in detecting diabetic retino.at,3. Diabetes Care ())"O(B>(()H8(()B !FB. Bril V, England &, 6ran1lin C , et al.O A+erican Acade+3 o* $eurolog3O A+erican Association o* $euro+uscular and Electrodiagnostic edicineO A+eri/ can Acade+3 o* #,3sical edicine and Re,abilitation. E0idence/based guideline> treat+ent o* .ain*ul diabetic neuro.at,3> re.ort o* t,e A+erican Acade+3 o* $eurolog3, t,e A+erican Association o* $euro+uscular and Electrodiagnostic edicine, and t,e A+erican Acade+3 o* #,3sical edicine and Re,abilitation. $eurolog3 ()%%OF">%FHE8%F"H !E). Boulton A&, Vini1 AI, Are;;o &C, et al.O A+erican Diabetes Association. Diabetic neuro.at,ies> a state+ent b3 t,e A+er/ ican Diabetes Association. Diabetes Care ())HO(E>BH"8B"( !E%. Kile D&, Tot, C. Association o* +et*or/ +in, ele0ated ,o+oc3steine, and +et,/ 3l+alonic acid le0els and clinicall3 4orsened diabetic .eri.,eral neuro.a/ t,3. Diabetes Care ()%)O!!>%H"8%"% !E(. 6ree+an R. $ot all neuro.at,3 in di/ abetes is o* diabetic etiolog3> di**erential diagnosis o* diabetic neuro.at,3. Curr Diab Re. ())BOB>:(!8:!% !E!. Vini1 AI, aser RE, itc,ell BD, 6ree+an R. Diabetic autono+ic neuro.at,3. Di/ abetes Care ())!O(">%HH!8%HFB !E:. S.allone V, Bella0ere 6, Scionti L, et al.O Diabetic $euro.at,3 Stud3 Crou. o* t,e Italian Societ3 o* Diabetolog3. Reco+/ +endations *or t,e use o* cardio0ascular tests in diagnosing diabetic autono+ic neuro.at,3. $utr etab Cardio0asc Dis ()%%O(%>"B8FE !EH. Boulton A&, Ar+strong DC, Albert S6, et al. Co+.re,ensi0e *oot e2a+ination and ris1 assess+ent> a re.ort o* t,e Tas1 6orce o* t,e 6oot Care Interest Crou. o* t,e A+erican Diabetes Association, 4it, endorse+ent b3 t,e A+erican Associa/ tion o* Clinical Endocrinologists. Di/ abetes Care ())EO!%>%"FB8%"EH !E". A+erican Diabetes Association. #eri/ .,eral arterial disease in .eo.le 4it, diabetes. Diabetes Care ())!O(">!!!!8 !!:% !EF. Li.s13 BA, Berendt AR, Cornia #B, et

al.O In*ectious Diseases Societ3 o* A+erica. ()%( In*ectious Diseases Societ3 o* A+erica clinical .ractice guideline *or t,e diagnosis and treat+ent o* diabetic *oot in*ections. Clin In*ect Dis ()%(OH:> e%!(8 e%F!

!EE. Bainbridge QE, Do**+an D&, Co4ie CC. Diabetes and ,earing i+.air+ent in t,e United States> audio+etric e0idence *ro+ t,e $ational Dealt, and $utrition E2a+ination Sur0e3, %BBB to ()):. Ann Intern ed ())EO%:B>%8%) !EB. Bainbridge QE, Do**+an D&, Co4ie CC. Ris1 *actors *or ,earing i+.air+ent a+ong U.S. adults 4it, diabetes> $a/ tional Dealt, and $utrition E2a+ination Sur0e3 %BBB/()):. Diabetes Care ()%%O !:>%H:)8%H:H !B). Li C, 6ord ES, V,ao C, Cro*t &B, Ballu; LS, o1dad AD. #re0alence o* sel*/ re.orted clinicall3 diagnosed slee. a./ nea according to obesit3 status in +en and 4o+en> $ational Dealt, and $u/ trition E2a+ination Sur0e3, ())H/())". #re0 ed ()%)OH%>%E8(! !B%. Kest SD, $icoll D&, Stradling &R. #re0a/ lence o* obstructi0e slee. a.noea in +en 4it, t3.e ( diabetes. T,ora2 ())"O"%> B:H8BH) !B(. 6oster CD, Sanders D, ill+an R, et al.O Slee. ADEAD Researc, Crou.. Obstructi0e slee. a.nea a+ong obese .atients 4it, t3.e ( diabetes. Diabetes Care ())BO!(>%)%F8%)%B !B!. S,a4 &E, #unjabi $ , Kilding &#, Alberti QC, Vi++et #V. Slee./disordered breat,ing and t3.e ( diabetes> a re.ort *ro+ t,e International Diabetes 6edera/ tion Tas1*orce on E.ide+iolog3 and #re/ 0ention. Diabetes Res Clin #ract ())EOE%> (8%( !B:. Clar1 & , Brancati 6L, Die,l A . T,e .re0alence and etiolog3 o* ele0ated a+inotrans*erase le0els in t,e United States. A+ & Castroenterol ())!OBE> B")8B"F !BH. El/Serag DB, Tran T, E0er,art &E. Di/ abetes increases t,e ris1 o* c,ronic li0er disease and ,e.atocellular carcino+a. Castroenterolog3 ()):O%(">:")8:"E !B". A+erican Castroenterological Associa/ tion. A+erican Castroenterological As/ sociation +edical .osition state+ent> nonalco,olic *att3 li0er disease. Castro/ enterolog3 ())(O%(!>%F)(8%F): !BF. D,indsa S, iller C, cK,irter CL, et al. Testosterone concentrations in di/ abetic and nondiabetic obese +en. Di/ abetes Care ()%)O!!>%%E"8%%B( !BE. B,asin S, Cunning,a+ CR, Da3es 6&, et al. Testosterone t,era.3 in +en 4it, androgen de5cienc3 s3ndro+es> an En/ docrine Societ3 clinical .ractice guide/ line. & Clin Endocrinol etab ()%)OBH> (H!"8(HHB !BB. Q,ader 'S, Dauod AS, El/Paderi SS, Al1a*ajei A, Bata3,a KP. #eriodontal status o* diabetics co+.ared 4it, non/ diabetics> a +eta/anal3sis. & Diabetes Co+.lications ())"O()>HB8"E :)). Darr] L, Vergnes &$, Courd3 #, Si2ou . E*5cac3 o* .eriodontal treat+ent on gl3cae+ic control in diabetic .atients>

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a +eta/anal3sis o* inter0entional studies. Diabetes etab ())EO!:>:BF8H)" International Diabetes 6ederation. Oral Dealt, *or #eo.le 4it, Diabetes. Brussels, International Diabetes 6ederation, ())B Su, S, Qi+ QK. Diabetes and cancer> is diabetes causall3 related to cancer^ Di/ abetes etab & ()%%O!H>%B!8%BE Cio0annucci E, Darlan D , Arc,er C, et al. Diabetes and cancer> a consensus re.ort. Diabetes Care ()%)O!!>%"F:8 %"EH &ang,orbani , Van Da+ R , Killett KC, Du 6B. S3ste+atic re0ie4 o* t3.e % and t3.e ( diabetes +ellitus and ris1 o* *racture. A+ & E.ide+iol ())FO%""> :BH8H)H Vestergaard #. Discre.ancies in bone +ineral densit3 and *racture ris1 in .a/ tients 4it, t3.e % and t3.e ( diabetesda +eta/anal3sis. Osteo.oros Int ())FO%E> :(F8::: 'a+a+oto , 'a+aguc,i T, 'a+auc,i , Qaji D, Sugi+oto T. Diabetic .atients ,a0e an increased ris1 o* 0ertebral *rac/ tures inde.endent o* B D or diabetic co+.lications. & Bone iner Res ())BO (:>F)(8F)B Sc,4art; AV, Vitting,o** E, Bauer DC, et al.O Stud3 o* Osteo.orotic 6ractures 7SO69 Researc, Crou.O Osteo.orotic 6ractures in en 7 rOS9 Researc, Crou.O Dealt,, Aging, and Bod3 Co+.osition 7Dealt, ABC9 Researc, Crou.. Associa/ tion o* B D and 6RAU score 4it, ris1 o* *racture in older adults 4it, t3.e ( di/ abetes. &A A ()%%O!)H>(%E:8(%B( Cu1ier+an T, Cerstein DC, Killia+son &D. Cogniti0e decline and de+entia in diabetesds3ste+atic o0er0ie4 o* .ro/ s.ecti0e obser0ational studies. Dia/ betologia ())HO:E>(:")8(:"B Biessels C&, Stae1enborg S, Brunner E, Bra3ne C, Sc,eltens #. Ris1 o* de+entia in diabetes +ellitus> a s3ste+atic re0ie4. Lancet $eurol ())"OH>":8F: O,ara T, Doi ', $ino+i3a T, et al. Clu/ cose tolerance status and ris1 o* de/ +entia in t,e co++unit3> t,e Disa3a+a stud3. $eurolog3 ()%%OFF>%%("8%%!: Launer L&, iller E, Killia+son &D, et al.O ACCORD I$D In0estigators. E**ects o* intensi0e glucose lo4ering on brain structure and *unction in .eo.le 4it, t3.e ( diabetes 7ACCORD I$D9> a rando+ised o.en/label substud3. Lancet $eurol ()%%O%)>B"B8 BFF Sil0erstein &, Qlingens+it, C, Co.eland QC, et al.O A+erican Diabetes Associa/ tion. Care o* c,ildren and adolescents 4it, t3.e % diabetes> a state+ent o* t,e A+erican Diabetes Association. Diabetes Care ())HO(E>%E"8(%( $ort,a+ EA, Anderson #&, Kert,er CA,

Karne CL, Adler RC, Andre4es D. $euro.s3c,ological co+.lications o*

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IDD in c,ildren ( 3ears a*ter disease onset. Diabetes Care %BBEO(%>!FB8!E: Ro0et &, Al0are; . Attentional *unc/ tioning in c,ildren and adolescents 4it, IDD . Diabetes Care %BBFO()>E)!8E%) Bjcrgaas , Ci+se R, Vi1 T, Sand T. Cogniti0e *unction in t3.e % diabetic c,ildren 4it, and 4it,out e.isodes o* se0ere ,3.ogl3cae+ia. Acta #aediatr %BBFOE">%:E8%H! $i+ri R, Keintrob $, Ben;a-uen D, O*an R, 6a3+an C, #,illi. . Insulin .u+. t,era.3 in 3out, 4it, t3.e % di/ abetes> a retros.ecti0e .aired stud3. #e/ diatrics ())"O%%F>(%("8(%!% Do3le EA, Kein;i+er SA, Ste**en AT, A,ern &A, Vincent , Ta+borlane KV. A rando+i;ed, .ros.ecti0e trial co+/ .aring t,e e*5cac3 o* continuous sub/ cutaneous insulin in*usion 4it, +ulti.le dail3 injections using insulin glargine. Diabetes Care ()):O(F>%HH:8 %HHE #erantie DC, Ku &, Qoller & , et al. Re/ gional brain 0olu+e di**erences associ/ ated 4it, ,3.ergl3ce+ia and se0ere ,3.ogl3ce+ia in 3out, 4it, t3.e % di/ abetes. Diabetes Care ())FO!)>(!!%8 (!!F a1i+attila S, al+berg/C`der Q, Da11inen A , et al. Brain +etabolic al/ terations in .atients 4it, t3.e % diabetes/ ,3.ergl3ce+ia/induced injur3. & Cereb Blood 6lo4 etab ()):O(:>%!B!8%!BB Qrant; &S, ac1 K&, Dodis D$, Liu CR, Liu CD, Qau*+an 6R. Earl3 onset o* subclinical at,erosclerosis in 3oung .ersons 4it, t3.e % diabetes. & #ediatr ()):O%:H>:H(8:HF &ar0isalo &, #utto/Laurila A, &artti L, et al. Carotid arter3 inti+a/+edia t,ic1/ ness in c,ildren 4it, t3.e % diabetes. Diabetes ())(OH%>:B!8:BE Daller &, Sa+3n , $ic,ols KK, et al. Radial arter3 tono+etr3 de+onstrates arterial sti**ness in c,ildren 4it, t3.e % diabetes. Diabetes Care ()):O(F>(B%%8 (B%F Orc,ard T&, 6orrest Q', Quller LD, Bec1er D&O #ittsburg, E.ide+iolog3 o* Diabetes Co+.lications Stud3. Li.id and blood .ressure treat+ent goals *or t3.e % diabetes> %)/3ear incidence data *ro+ t,e #ittsburg, E.ide+iolog3 o* Diabetes Co+.lications Stud3. Diabetes Care ())%O(:>%)H!8%)HB Qa0e3 RE, Allada V, Daniels SR, et al. Cardio0ascular ris1 reduction in ,ig,/ ris1 .ediatric .atients> a scienti5c state+ent *ro+ t,e A+erican Deart As/ sociation E2.ert #anel on #o.ulation and #re0ention ScienceO t,e Councils on Cardio0ascular Disease in t,e 'oung, E.ide+iolog3 and #re0ention, $utri/ tion, #,3sical Acti0it3 and etabolis+, Dig, Blood #ressure Researc,, Cardio/ 0ascular $ursing, and t,e Qidne3 in

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Outco+es Researc,> endorsed b3 t,e A+erican Acade+3 o* #ediatrics. Circu/ lation ())"O%%:>(F%)8(F!E cCrindle BK, Urbina E , Dennison BA, et al. Drug t,era.3 o* ,ig,/ris1 li.id abnor+alities in c,ildren and adoles/ cents> a scienti5c state+ent *ro+ t,e A+erican Deart Association At,eroscle/ rosis, D3.ertension, and Obesit3 in 'out, Co++ittee, Council o* Cardio/ 0ascular Disease in t,e 'oung, 4it, t,e Council on Cardio0ascular $ursing. Circulation ())FO%%H>%B:E8%B"F Salo #, Vii1ari &, Da+alainen , et al. Seru+ c,olesterol ester *att3 acids in F/ and %!/+ont,/old c,ildren in a .ro/ s.ecti0e rando+i;ed trial o* a lo4/ saturated *at, lo4/c,olesterol diet> t,e STRI# bab3 .roject. S.ecial Tur1u cor/ onar3 Ris1 *actor Inter0ention #roject *or c,ildren. Acta #aediatr %BBBOEE> H)H8H%( T,e Dietar3 Inter0ention Stud3 in C,il/ dren 7DISC9. T,e Kriting Crou. *or t,e DISC Collaborati0e Researc, Crou.. E*5cac3 and sa*et3 o* lo4ering dietar3 inta1e o* *at and c,olesterol in c,ildren 4it, ele0ated lo4/densit3 li.o.rotein c,olesterol. &A A %BBHO(F!>%:(B8%:!H cCrindle BK, Ose L, arais AD. E*5/ cac3 and sa*et3 o* ator0astatin in c,ildren and adolescents 4it, *a+ilial ,3.erc,o/ lesterole+ia or se0ere ,3.erli.ide+ia> a +ulticenter, rando+i;ed, .lacebo/ controlled trial. & #ediatr ())!O%:!>F:8E) de &ong, S, Lilien R, o.<t Roodt &, Stroes ES, Ba11er DD, Qastelein &&. Earl3 statin t,era.3 restores endot,elial *unc/ tion in c,ildren 4it, *a+ilial ,3.erc,o/ lesterole+ia. & A+ Coll Cardiol ())(O:)> (%%F8(%(% Kieg+an A, Dutten BA, de Croot E, et al. E*5cac3 and sa*et3 o* statin t,era.3 in c,ildren 4it, *a+ilial ,3.erc,olesterol/ e+ia> a rando+i;ed controlled trial. &A A ()):O(B(>!!%8!!F C,o 'D, Craig E, Ding S, et al. i/ cro0ascular co+.lications assess+ent in adolescents 4it, (/ to H/3r duration o* t3.e % diabetes *ro+ %BB) to ())". #e/ diatr Diabetes ()%%O%(>"E(8"EB Dol+es CQ. Screening *or coeliac dis/ ease in t3.e % diabetes. Arc, Dis C,ild ())(OEF>:BH8:BE Re4ers , Liu E, Si++ons &, Redondo &, Do**enberg E&. Celiac disease asso/ ciated 4it, t3.e % diabetes +ellitus. Endocrinol etab Clin $ort, A+ ()):O !!>%BF8(%:, 2i Dusb3 S, Qolet;1o S, Qor.ona3/S;abX IR, et al.O ES#CDA$ Kor1ing Crou. on Coeliac Disease DiagnosisO ES#CDA$ Castroenterolog3 Co++itteeO Euro.ean Societ3 *or #ediatric Castroenterolog3, De.atolog3, and $utrition. Euro.ean Societ3 *or #ediatric Castroenterolog3, De.atolog3, and $utrition guidelines *or

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t,e diagnosis o* coeliac disease. & #ediatr Castroenterol $utr ()%(OH:>%!"8%") Qur..a Q, As,orn , Iltanen S, et al. Celiac disease 4it,out 0illous atro.,3 in c,ildren> a .ros.ecti0e stud3. & #ediatr ()%)O%HF>!F!8!E) Abid $, cClone O, Card4ell C, cCallion K, Carson D. Clinical and +etabolic e**ects o* gluten *ree diet in c,ildren 4it, t3.e % diabetes and coeliac disease. #ediatr Diabetes ()%%O%(>!((8 !(H Rold an B, Alonso , Barrio R. T,3roid autoi++unit3 in c,ildren and adoles/ cents 4it, T3.e % diabetes +ellitus. Di/ abetes $utr etab %BBBO%(>(F8!% Triolo T , Ar+strong TQ, c6ann Q, et al. Additional autoi++une disease *ound in !!I o* .atients at t3.e % di/ abetes onset. Diabetes Care ()%%O!:> %(%%8%(%! Qordonouri O, Deiss D, Danne T, Doro4 A, Bassir C, Cru_ters/Qieslic, A. #re/ dicti0it3 o* t,3roid autoantibodies *or t,e de0elo.+ent o* t,3roid disor/ ders in c,ildren and adolescents 4it, T3.e % diabetes. Diabet ed ())(O%B> H%E8H(% o,n A, Di ic,ele S, Di Lu;io R, Tu+ini S, C,iarelli 6. T,e e**ect o* sub/ clinical ,3.ot,3roidis+ on +etabolic control in c,ildren and adolescents 4it, T3.e % diabetes +ellitus. Diabet ed ())(O%B>F)8F! C,ase D#, Carg SQ, Coc1er,a+ RS, Kilco2 KD, Kalra0ens #A. T,3roid ,or+one re.lace+ent and gro4t, o* c,ildren 4it, subclinical ,3.ot,3roid/ is+ and diabetes. Diabet ed %BB)OF> (BB8!)! A+erican Diabetes Association. Diabetes care in t,e sc,ool and da3 care setting. Diabetes Care ()%)O!!7Su..l. %9>SF)8 SF: Arnett &&. E+erging adult,ood. A t,eor3 o* de0elo.+ent *ro+ t,e late teens t,roug, t,e t4enties. A+ #s3c,ol ()))O HH>:"B8:E) Keissberg/Benc,ell &, Kol.ert D, Anderson B&. Transitioning *ro+ .edi/ atric to adult care> a ne4 a..roac, to t,e .ost/adolescent 3oung .erson 4it, t3.e % diabetes. Diabetes Care ())FO!)> (::%8(::" #eters A, La**el L, t,e A+erican Diabetes Association Transitions Kor1ing Crou.. Diabetes care *or e+erging adults> rec/ o++endations *or transition *ro+ .e/ diatric to adult diabetes care s3ste+s> a .osition state+ent o* t,e A+erican Diabetes Association, 4it, re.resenta/ tion b3 t,e A+erican College o* Osteo/ .at,ic 6a+il3 #,3sicians, t,e A+erican Acade+3 o* #ediatrics, t,e A+erican Association o* Clinical Endocrinologists, t,e A+erican Osteo.at,ic Association, t,e Centers *or Disease Control and

#re0ention, C,ildren 4it, Diabetes, T,e

Endocrine Societ3, t,e International Societ3 *or #ediatric and Adolescent Diabetes, &u0enile Diabetes Researc, 6oundation International, t,e $ational Diabetes Education #rogra+, and t,e #ediatric Endocrine Societ3 7*or+erl3 La4son Kil1ins #ediatric Endocrine Societ39. Diabetes Care ()%%O!:>(:FF8 (:EH ::". Br3den QS, #e0eler RC, Stein A, $eil A, a3ou RA, Dunger DB. Clinical and .s3c,ological course o* diabetes *ro+ adolescence to 3oung adult,ood> a lon/ gitudinal co,ort stud3. Diabetes Care ())%O(:>%H!"8%H:) ::F. Laing S#, &ones E, S4erdlo4 A&, Burden AC, Catling K. #s3c,osocial and socioecono+ic ris1 *actors *or .re+ature deat, in 3oung .eo.le 4it, t3.e % di/ abetes. Diabetes Care ())HO(E>%"%E8 %"(! ::E. E..ens C, Craig E, Cusu+ano &, et al. #re0alence o* diabetes co+.lica/ tions in adolescents 4it, t3.e ( co+/ .ared 4it, t3.e % diabetes. Diabetes Care ())"O(B>%!))8%!)" ::B. Dattersle3 A, Bruining &, S,ield &, $jolstad #, Donag,ue QC. T,e diagnosis and +anage+ent o* +onogenic diabetes in c,ildren and adolescents. #ediatr Di/ abetes ())BO%)7Su..l. %(9>!!8:( :H). Coo.er KO, Dernande;/Dia; S, Arbogast #C, et al. ajor congenital +al*or+ations a*ter 5rst/tri+ester e2.o/ sure to ACE in,ibitors. $ Engl & ed ())"O!H:>(::!8(:H% :H%. A+erican Diabetes Association. #re/ conce.tion care o* 4o+en 4it, diabetes. Diabetes Care ()):O(F7Su..l. %9>SF"8 SFE :H(. Qir1+an , Briscoe V&, Clar1 $, et al. Diabetes in older adults. Diabetes Care ()%(O!H>("H)8("": :H!. Curb &D, #ressel SL, Cutler &A, et al.O S3stolic D3.ertension in t,e Elderl3 #rogra+ Coo.erati0e Researc, Crou.. E**ect o* diuretic/based anti,3.ertensi0e treat+ent on cardio0ascular disease ris1 in older diabetic .atients 4it, isolated s3stolic ,3.ertension. &A A %BB"O(F"> %EE"8%EB( :H:. Bec1ett $S, #eters R, 6letc,er AE, et al.O D'VET Stud3 Crou.. Treat+ent o* ,3/ .ertension in .atients E) 3ears o* age or older. $ Engl & ed ())EO!HE>%EEF8 %EBE :HH. oran A, Dunit; &, $at,an B, Saeed A, Dol+e B, T,o+as K. C3stic 5brosis/ related diabetes> current trends in .re0alence, incidence, and +ortalit3. Diabetes Care ())BO!(>%"("8%"!% :H". oran A, Brun;ell C, Co,en RC, et al.O C6RD Cuidelines Co++ittee. Clinical care guidelines *or c3stic 5brosis/ related diabetes> a .osition state+ent

o* t,e A+erican Diabetes Association and a clinical .ractice guideline o* t,e C3stic 6ibrosis 6oundation, endorsed b3 t,e

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#ediatric Endocrine Societ3. Diabetes Care ()%)O!!>("BF8(F)E Cle+ent S, Brait,4aite SS, agee 6, et al.O A+erican Diabetes Association Diabetes in Dos.itals Kriting Co++it/ tee. anage+ent o* diabetes and ,3/ .ergl3ce+ia in ,os.itals. Diabetes Care ()):O(F>HH!8HB% 0an den Berg,e C, Kouters #, Kee1ers 6, et al. Intensi0e insulin t,era.3 in criticall3 ill .atients. $ Engl & ed ())%O !:H>%!HB8%!"F al+berg Q, $or,a++ar A, Kedel D, R3d]n L. Cl3co+etabolic state at ad/ +ission> i+.ortant ris1 +ar1er o* +or/ talit3 in con0entionall3 treated .atients 4it, diabetes +ellitus and acute +3o/ cardial in*arction> long/ter+ results *ro+ t,e Diabetes and Insulin/Clucose In/ *usion in Acute 3ocardial In*arction 7DICA I9 stud3. Circulation %BBBOBB> ("("8("!( Kiener RS, Kiener DC, Larson R&. Bene5ts and ris1s o* tig,t glucose control in criticall3 ill adults> a +eta/anal3sis. &A A ())EO!))>B!!8B:: Brun1,orst 6 , Engel C, Bloos 6, et al.O Cer+an Co+.etence $et4or1 Se.sis 7Se.$et9. Intensi0e insulin t,era.3 and .entastarc, resuscitation in se0ere se./ sis. $ Engl & ed ())EO!HE>%(H8%!B 6in*er S, C,ittoc1 DR, Su S', et al.O $ICE/SUCAR Stud3 In0estigators. In/ tensi0e 0ersus con0entional glucose control in criticall3 ill .atients. $ Engl & ed ())BO!")>%(E!8%(BF Qrinsle3 &S, Cro0er A. Se0ere ,3.ogl3/ ce+ia in criticall3 ill .atients> ris1 *actors and outco+es. Crit Care ed ())FO!H> (("(8(("F Van den Berg,e C, Kil+er A, Der+ans C, et al. Intensi0e insulin t,era.3 in t,e +edical ICU. $ Engl & ed ())"O!H:> ::B8:"% Criesdale DE, de Sou;a R&, 0an Da+ R , et al. Intensi0e insulin t,era.3 and +ortalit3 a+ong criticall3 ill .atients> a +eta/anal3sis including $ICE/SUCAR stud3 data. C A& ())BO%E)>E(%8E(F Saude1 CD, Der+an KD, Sac1s DB, Bergenstal R , Edel+an D, Da0idson B. A ne4 loo1 at screening and di/ agnosing diabetes +ellitus. & Clin En/ docrinol etab ())EOB!>(::F8(:H! Cr3er #E, Da0is S$, S,a+oon D. D3/ .ogl3ce+ia in diabetes. Diabetes Care ())!O(">%B)(8%B%( og,issi ES, Qor3t1o4s1i T, Di$ardo , et al.O A+erican Association o* Clin/ ical EndocrinologistsO A+erican Diabetes Association. A+erican Association o* Clinical Endocrinologists and A+erican Diabetes Association consensus state+ent on in.atient gl3ce+ic control. Diabetes Care ())BO!(>%%%B8%%!% Dsu CK, Sun S6, Lin SL, Duang DD, Kong Q6. oderate glucose control re/ sults in less negati0e nitrogen balances in

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+edical intensi0e care unit .atients> a rando+i;ed, controlled stud3. Crit Care ()%(O%">RH" U+.ierre; CE, Dell+an R, Qor3t1o4s1i T, et al.O Endocrine Societ3. anage/ +ent o* ,3.ergl3ce+ia in ,os.itali;ed .atients in non/critical care setting> an Endocrine Societ3 clinical .ractice guideline. & Clin Endocrinol etab ()%(OBF>%"8!E Bernard &B, uno; C, Dar.er &, uriello , Rico E, Bald4in D. Treat+ent o* in/ .atient ,3.ergl3ce+ia beginning in t,e e+ergenc3 de.art+ent> a rando+i;ed trial using insulins as.art and dete+ir co+.ared 4it, usual care. & Dos. ed ()%%O">(FB8(E: C;osno4s1i PA, S4anson & , Lobo BL, Bro3les &E, Deaton #R, 6inc, CQ. E0al/ uation o* gl3ce+ic control *ollo4ing discontinuation o* an intensi0e insulin .rotocol. & Dos. ed ())BO:>(E8!: S,o+ali I, Derr DL, Dill #C, #e,li0ano0a , S,arretts & , agee 6. Con0ersion *ro+ intra0enous insulin to subcutaneous insulin a*ter cardio0ascu/ lar surger3> Transition to Target stud3. Diabetes Tec,nol T,er ()%%O%!>%(%8 %(" Bald4in D, Vander &, uno; C, et al. A rando+i;ed trial o* t4o 4eig,t/based doses o* insulin glargine and glulisine in ,os.itali;ed subjects 4it, t3.e ( di/ abetes and renal insu*5cienc3. Diabetes Care ()%(O!H>%BF)8%BF: U+.ierre; CE, S+ile3 D, &acobs S, et al. Rando+i;ed stud3 o* basal/bolus insulin t,era.3 in t,e in.atient +an/ age+ent o* .atients 4it, t3.e ( diabetes undergoing general surger3 7RABBIT ( surger39. Diabetes Care ()%%O!:> (H"8("% #as-uel 6&, S.iegel+an R, cCaule3 , et al. D3.ergl3ce+ia during total .arenteral nutrition> an i+.ortant +ar1er o* .oor outco+e and +ortalit3 in ,os.itali;ed .a/ tients. Diabetes Care ()%)O!!>F!B8 F:% Sc,ni..er &L, Liang CL, $du+ele CD, #endergrass L. E**ects o* a co+.ut/ eri;ed order set on t,e in.atient +anage+ent o* ,3.ergl3ce+ia> a cluster/ rando+i;ed controlled trial. Endocr #ract ()%)O%">()B8(%E Ke2ler D&, S,rader #, Burns S , Cagliero E. E**ecti0eness o* a co+.uter/ i;ed insulin order te+.late in general +edical in.atients 4it, t3.e ( diabetes> a cluster rando+i;ed trial. Diabetes Care ()%)O!!>(%E%8(%E! 6urnar3 A#, Brait,4aite SS. E**ects o* outco+e on in/,os.ital transition *ro+ intra0enous insulin in*usion to sub/ cutaneous t,era.3. A+ & Cardiol ())"O

BE>HHF8 H": :E). Sc,a*er RC, Bo,annon B, 6ran; &, et al.O A+erican Diabetes Association. Diabetes nutrition reco++endations *or

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,ealt, care institutions. Diabetes Care ()):O(F7Su..l. %9>SHH8 SHF Curll , Dinardo , $osc,ese , Qor3t1o4s1i T. enu selection, gl3/ cae+ic control and satis*action 4it, standard and .atient/controlled consis/ tent carbo,3drate +eal .lans in ,os.i/ talised .atients 4it, diabetes. Pual Sa* Dealt, Care ()%)O%B>!HH8!HB odic B, Qo;a1 A, Siedlec1i SL, et al. Do 4e 1no4 4,at our .atients 4it, di/ abetes are eating in t,e ,os.ital^ Di/ abetes S.ectru+ ()%%O(:>%))8%)" Bouc,er &L, S4i*t CS, 6ran; &, et al. In.atient +anage+ent o* diabetes and ,3.ergl3ce+ia> i+.lications *or nutri/ tion .ractice and t,e *ood and nutrition .ro*essional. & A+ Diet Assoc ())FO%)F> %)H8%%% Qor3t1o4s1i T, Salata R&, Qoerbel CL, et al. Insulin t,era.3 and gl3ce+ic con/ trol in ,os.itali;ed .atients 4it, di/ abetes during enteral nutrition t,era.3> a rando+i;ed controlled clinical trial. Diabetes Care ())BO!(>HB:8HB" U+.ierre; CE. Basal 0ersus sliding/scale regular insulin in ,os.itali;ed .atients 4it, ,3.ergl3ce+ia during enteral nu/ trition t,era.3. Diabetes Care ())BO!(> FH%8FH! Qlono** DC, #er; &6. Assisted +onitoring o* blood glucose> s.ecial sa*et3 needs *or a ne4 .aradig+ in testing glucose. & Diabetes Sci Tec, ()%)O:>%)(F8%)!% D<Ora;io #, Burnett RK, 6og,/Andersen $, et al.O International 6ederation o* Clinical C,e+istr3 Scienti5c Di0ision Kor1ing Crou. on Selecti0e Electrodes and #oint o* Care Testing. A..ro0ed I6CC reco++endation on re.orting re/ sults *or blood glucose 7abbre0iated9. Clin C,e+ ())HOH%>%HF!8%HF" Dungan Q, C,a.+an &, Brait,4aite SS, Buse &. Clucose +easure+ent> con*ound/ ing issues in setting targets *or in.atient +anage+ent. Diabetes Care ())FO!)>:)!8 :)B Bo3d &C, Bruns DE. Pualit3 s.eci5ca/ tions *or glucose +eters> assess+ent b3 si+ulation +odeling o* errors in insulin dose. Clin C,e+ ())%O:F>()B8(%: S,e..erd S, cClaran &, #,illi.s CO, et al. Disc,arge .lanning *ro+ ,os.ital to ,o+e. Coc,rane Database S3st Re0 ()%)O7%9>CD)))!%! Agenc3 *or Dealt,care Researc, and Pualit3. Ad0erse e0ents a*ter ,os.ital disc,arge Larticle onlineM. A0ailable *ro+ ,tt.>@ @. snet .a ,r -. go0@.ri+er.as. 2^.ri/ +erIDH%%. Accessed (H August ()%( A+erican Diabetes Association. Diabetes and e+.lo3+ent. Diabetes Care ()%%O !:7Su..l. %9>SE(8 SE" A+erican Diabetes Association. Diabetes and dri0ing. Diabetes Care ()%(O!H

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:B:. A+erican Diabetes Association. Diabetes +anage+ent in correctional institutions. Diabetes Care ()%%O!:7Su..l. %9>SFH8SE% :BH. Doerger T&, Segel &E, Cregg EK, Saaddine &B. Is gl3ce+ic control i+/ .ro0ing in U.S. adults^ Diabetes Care ())EO!%>E%8E" :B". C,eung B , Ong QL, C,ern3 SS, S,a+ #C, Tso AK, La+ QS. Diabetes .re0a/ lence and t,era.eutic target ac,ie0e+ent in t,e United States, %BBB to ())". A+ & ed ())BO%((>::!8:H! :BF. Kang &, Ceiss LS, C,eng '&, et al. Long/ ter+ and recent .rogress in blood .res/ sure le0els a+ong U.S. adults 4it, diagnosed diabetes, %BEE/())E. Dia/ betes Care ()%%O!:>%HFB8%HE% :BE. Qerr EA, Deisler , Qrein SL, et al. Be/ 3ond co+orbidit3 counts> ,o4 do co/ +orbidit3 t3.e and se0erit3 inAuence diabetes .atients< treat+ent .riorities and sel*/+anage+ent^ & Cen Intern ed ())FO((>%"!H8%":) :BB. 6ernande; A, Sc,illinger D, Karton E , et al. Language barriers, .,3sician/ .atient language concordance, and gl3/ ce+ic control a+ong insured Latinos 4it, diabetes> t,e Diabetes Stud3 o* $ort,ern Cali*ornia 7DISTA$CE9. & Cen Intern ed ()%%O(">%F)8%F" H)). T,e Robert Kood &o,nson 6ounda/ tion. E0idence *or better care> diabetes. A0ailable at ,tt.>@@444.i+.ro0ingc,ronic care.org@inde2..,.^.dDiabetesesdE". Accessed (" $o0e+ber ()%( H)%. Cole+an Q, Austin BT, Brac, C, Kagner ED. E0idence on t,e C,ronic Care odel in t,e ne4 +illenniu+. Dealt, A** 7 ill4ood9 ())BO(E>FH8EH H)(. #arc,+an L, Veber &E, Ro+ero RR, #ug, &A. Ris1 o* coronar3 arter3 disease in t3.e ( diabetes and t,e deli0er3 o* care consistent 4it, t,e c,ronic care +odel in .ri+ar3 care settings> a STAR$et stud3. ed Care ())FO:H>%%(B8%%!: H)!. Da0idson B. Do4 our current +edical care s3ste+ *ails .eo.le 4it, diabetes> lac1 o* ti+el3, a..ro.riate clinical deci/ sions. Diabetes Care ())BO!(>!F)8!F( H):. Crant RK, #abon/$au L, Ross Q , 'ouatt E&, #andiscio &C, #ar1 ER. Di/ abetes oral +edication initiation and intensi5cation> .atient 0ie4s co+.ared 4it, current treat+ent guidelines. Di/ abetes Educ ()%%O!F>FE8E: H)H. Sc,illinger D, #iette &, Cru+bac, Q, et al. Closing t,e loo.> .,3sician co++uni/ cation 4it, diabetic .atients 4,o ,a0e lo4 ,ealt, literac3. Arc, Intern ed ())!O%"!>E!8B) H)". Rosal C, Oc1ene IS, Restre.o A, et al. Rando+i;ed trial o* a literac3/sensiti0e, culturall3 tailored diabetes sel*/ +anage+ent inter0ention *or lo4/ inco+e Latinos> Latinos en Control. Diabetes Care ()%%O!:>E!E8E:: H)F. Osborn C', Ca0anaug, Q, Kallston QA, et al. Dealt, literac3 e2.lains racial

dis.arities in diabetes +edication ad/ ,erence. & Dealt, Co++un ()%%O%" 7Su..l. !9>("E8(FE H)E. Rot,+an R, alone R, Br3ant B, Dorlen C, DeKalt D, #ignone . T,e relation/ s,i. bet4een literac3 and gl3ce+ic control in a diabetes disease/+anage+ent .ro/ gra+. Diabetes Educ ()):O!)>("!8 (F! H)B. O<Connor #&, S.erl/Dillen & , Rus, KA, et al. I+.act o* electronic ,ealt, record clinical decision su..ort on diabetes care> a rando+i;ed trial. Ann 6a+ ed ()%%OB>%(8(% H%). Carg AU, Ad,i1ari $Q, cDonald D, et al. E**ects o* co+.uteri;ed clinical decision su..ort s3ste+s on .ractitioner .er*or/ +ance and .atient outco+es> a s3ste+atic re0ie4. &A A ())HO(B!>%((!8%(!E H%%. S+it, SA, S,a, $D, Br3ant SC, et al.O E0idens Researc, Crou.. C,ronic care +odel and s,ared care in diabetes> ran/ do+i;ed trial o* an electronic decision su..ort s3ste+. a3o Clin #roc ())EO E!>F:F8FHF H%(. cLean DL, cAlister 6A, &o,nson &A, et al.O SCRI#/DT$ In0estigators. A ran/ do+i;ed trial o* t,e e**ect o* co++unit3 .,ar+acist and nurse care on i+.ro0ing blood .ressure +anage+ent in .atients 4it, diabetes +ellitus> Stud3 o* Cardio/ 0ascular Ris1 Inter0ention b3 #,ar+a/ cists8D3.ertension 7SCRI#/DT$9. Arc, Intern ed ())EO%"E>(!HH8(!"% H%!. Kubben D#, Vi0ian E . E**ects o* .,ar/ +acist out.atient inter0entions on adults 4it, diabetes +ellitus> a s3ste+atic re0ie4. #,ar+acot,era.3 ())EO(E>:(%8 :!" H%:. Da0idson B, Ansari A, Qarlan V&. E**ect o* a nurse/directed diabetes disease +anage+ent .rogra+ on urgent care@ e+ergenc3 roo+ 0isits and ,os.ital/ i;ations in a +inorit3 .o.ulation. Di/ abetes Care ())FO!)>((:8((F H%H. Stone RA, Rao RD, Se0ic1 A, et al. Acti0e care +anage+ent su..orted b3 ,o+e tele+onitoring in 0eterans 4it, t3.e ( diabetes> t,e DiaTel rando+i;ed controlled trial. Diabetes Care ()%)O!!> :FE8:E: H%". Beri1ai #, e3er # , Qa;laus1aite R, Sa0o3 B, Qo;i1 Q, 6ogel*eld L. Cain in .atients< 1no4ledge o* diabetes +an/ age+ent targets is associated 4it, better gl3ce+ic control. Diabetes Care ())FO !)>%HEF8%HEB H%F. Tricco AC, I0ers $ , Cri+s,a4 & , et al. E**ecti0eness o* -ualit3 i+.ro0e/ +ent strategies on t,e +anage+ent o* diabetes> a s3ste+atic re0ie4 and +eta/ anal3sis. Lancet ()%(O!FB>((H(8(("% H%E. O<Connor #&, Bod1in $L, 6rad1in &, et al. Diabetes .er*or+ance +easures> current status and *uture directions. Di/ abetes Care ()%%O!:>%"H%8%"HB H%B. #ei1es D, C,en A, Sc,ore &, Bro4n R.

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bene5ciaries> %H rando+i;ed trials. &A A ())BO!)%>")!8"%E H(). 6ei*er C, $e+et, L, $ietert #&, et al. Di*/ *erent .at,s to ,ig,/-ualit3 care> t,ree arc,et3.es o* to./.er*or+ing .ractice sites. Ann 6a+ ed ())FOH>(!!8(:% H(%. Cebul RD, Lo0e TE, &ain AQ, Debert C&. Electronic ,ealt, records and -ualit3 o* diabetes care. $ Engl & ed ()%%O!"H> E(H8E!! H((. Ralston &D, Dirsc, IB, Doat, &, ullen , C,eadle A, Coldberg DI. Keb/ based collaborati0e care *or t3.e ( diabetes> a .ilot rando+i;ed trial. Diabetes Care ())BO!(>(!:8(!B

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in $ort, Carolina. & #ublic Dealt, anag #ract ())EO%:7Su..l.9>SF!8SE% H(". Bojad;ie0s1i T, Cabba3 RA. #atient/ centered +edical ,o+e and diabetes. Diabetes Care ()%%O!:>%):F8%)H! H(F. Rosent,al B, Cutler D , 6eder &. T,e ACO rulesdstri1ing t,e balance be/ t4een .artici.ation and trans*or+ati0e .otential. $ Engl & ed ()%%O!"H>e" H(E. Kas,ington AE, Li.stein SD. T,e #a/ tient/Centered Outco+es Researc, In/ stituted.ro+oting better in*or+ation, decisions, and ,ealt,. $ Engl & ed ()%%O!"H>e!%