Glycated Hemoglobin

12/22/2010 Glycated hemoglobin - Wikipedia, the f…
Glycated hemoglobin
From Wikipedia, the free encyclopedia
Glycated hemoglobin (glycosylated hemoglobin, hemoglobin A1c, HbA1c, A1C, or Hb1c; sometimes also
HbA1c) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over
prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma
glucose. Normal levels of glucose produce a normal amount of glycated hemoglobin. As the average amount of
plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. This serves as a
marker for average blood glucose levels over the previous months prior to the measurement.
The 2010 American Diabetes Association Standards of Medical Care in Diabetes added the A1c ≥ 6.5% as
another criterion for the diagnosis of diabetes,[1] but this is controversial and has not been universally adopted.[2]
In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have
been associated with cardiovascular disease, nephropathy, and retinopathy. Monitoring the HbA1c in type-1
diabetic patients may improve treatment.[3]
Contents
1 History
2 Underlying principle
3 Measuring A1C
3.1 Switch to IFCC units
4 Interpretation of results
5 Indications and use
6 Modification by exercise training
7 Standardization & traceability
8 See also
9 References
10 External links
History
Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a
chromatographic column.[4] It was first characterized as a glycoprotein by Bookchin and Gallop in 1968.[5] Its
increase in diabetes was first described in 1969 by Samuel Rahbar et. al.[6] The reactions leading to its formation
were characterized by Bunn and his co-workers in 1975.[7] The use of hemoglobin A1c for monitoring the degree
of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig
and coworkers.[8]
Underlying principle
…wikipedia.org/…/Glycated_hemoglobin 1/8
In the normal 120-day lifespan of the red blood cell, glucose molecules react with hemoglobin, forming glycated
hemoglobin. In individuals with poorly controlled diabetes, the quantities of these glycated hemoglobins are much
higher than in healthy people.
Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell,
therefore, reflects the average level of glucose to which the cell has been exposed during its life-cycle. Measuring
glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The
HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months.
Some researchers state that the major proportion of its value is related to a rather shorter period of two to four
weeks.[9]
The 2010 American Diabetes Association Standards of Medical Care in Diabetes added the A1c ≥ 6.5% as
another criterion for the diagnosis of diabetes,[10] but this is controversial and has not been universally adopted.[2]
Measuring A1C
There are a number of techniques used to measure A1C.
Laboratories use:
high-performance liquid chromatography (HPLC): The HbA1c result is calculated as a ratio to total
haemoglobin by using a chromatogram.
immunoassay
Point of care (e.g. doctor's surgery) devices use:
immunoassay
boronate affinity chromatography
In the United States, POC A1C tests are certified by the National Glycohemoglobin Standardization Program
(NGSP) to standardise them against the results of the 1993 Diabetes Control and Complications Trial (DCCT).[11]
Switch to IFCC units
The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) and
International Diabetes Federation (IDF) have agreed that, in the future, HbA1c is to be reported in the International
Federation of Clinical Chemistry (IFCC) units.[12] IFCC reporting was introduced in Europe except for the UK in
2003,[13] and the UK has as of 1 June 2009 introduced dual reporting[14] until 1 June 2011.[15]
Conversion between the units is by the following equation:[16] IFCC-HbA1c (mmol/mol) = [DCCT-HbA1c (%) -
2.15] × 10.929
DCCT- HbA1c IFCC-HbA1c

(%) (mmol/mol)
4.0 20
5.0 31
6.0 42
6.5 48
7.0 53
7.5 59
8.0 64
9.0 75
10.0 86
Interpretation of results
Laboratory results may differ depending on the analytical technique, the age of the subject, and biological variation
among individuals. Two individuals with the same average blood sugar can have A1C values that differ by as much
as 3 percentage points. Results can be unreliable in many circumstances, such as after blood loss, for example, after
surgery, blood transfusions, anemia, or high erythrocyte turnover; in the presence of chronic renal or liver disease;
after administration of high-dose vitamin C; or erythropoetin treatment.[17] In general, the reference range (that
found in healthy persons), is about 4%–5.9%.[18]
Higher levels of HbA1c are found in people with persistently elevated blood sugar, as in diabetes mellitus. While
diabetic patient treatment goals vary, many include a target range of HbA1c values. A diabetic person with good
glucose control has a HbA1c level that is close to or within the reference range. The International Diabetes
Federation and American College of Endocrinology recommend HbA1c values below 6.5%, while
American Diabetes Association recommends that the HbA1c be below 7.0% for most patients.[19] Recent
results from large trials suggest that a target below 7% may be excessive: Below 7% the health benefits of reduced
A1C become smaller, and the intensive glycemic control required to reach this level leads to an increased rate of
dangerous hypoglycemic episodes.[20] A retrospective study of 47,970 diabetes patients found that patients with an
A1C greater than 6.5% had an increased mortality rate.[21] Practitioners must consider an individual patient's health,
his/her risk of hypoglycemia, and his/her specific health risks when setting a target A1C level. For example, patients
at high risk of microvascular complications may gain further benefits from reducing A1C below 7%. Because
patients are responsible for averting or responding to their own hypoglycemic episodes, the patient's input and the
doctor's assessment of the patient's self-care skills are also important.
A high HbA1c represents poor glucose control. However, a 'good' HbA1c in a patient with diabetes can still be
riddled with a history of recent hypoglycemia, or even spikes of hyperglycemia. Regular blood glucose monitoring is
still the best method for the analysis of overall vascular health with respect to blood sugar control. Often, patients
with diabetes mellitus are scolded by their doctors[citation needed] for having an HbA1c which is too low, because a
lower A1C would indicate a likelihood of frequent hypoglycemia in the recent past. This is often assessed with
blood sugar data, and receptions are typically mixed. A balance of long-term health (hyperglycemia prevention)
versus short-term health (hypoglycemia prevention) is always a constant concern for both patients and their doctors.
Doctors are especially sensitive about lower level HbA1c's with patients who regularly drive, this being a prime
example of a short-term motivation for preventing hypoglycemia. Many diabetics have died behind the wheel as a
result of a low blood sugar[citation needed], especially for the reason that frequent hypoglycemia results in a higher
tolerance (sometimes, the patient is seized with a feeling of panic, an increased heart rate, profuse sweating, etc.) for
the condition, and some patients may not even consciously realize their blood sugar has dropped to dangerous
levels. In addition to acquired tolerance, the use of alcohol and certain drugs (marijuana, for example) can create
moderately similar symptoms to those of hypoglycemia[citation needed] (especially when used in combination) and
for this reason the patient may not realize he/she has developed hypoglycemia.
Persistent elevations in blood sugar (and, therefore, HbA1c) increase the risk for the long-term vascular
complications of diabetes such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness,
erectile dysfunction, neuropathy (loss of sensation, especially in the feet), gangrene, and gastroparesis (slowed
emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery
such as poor wound healing.
Lower-than-expected levels of HbA1c can be seen in people with shortened red blood cell lifespan, such as with
glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, or any other condition causing premature red
blood cell death. On the converse, higher-than-expected levels can be seen in people with a longer red blood cell
lifespan, such as with Vitamin B12 or folate deficiency.[2]
The approximate mapping between HbA1c values and eAG (estimated average glucose) measurements is given by
the following equation:[17]
eAG(mg/dl) = 28.7 × A1C − 46.7

eAG(mmol/l) = 1.59 × A1C − 2.59
Data in parentheses are 95% confidence intervals
HbA1c eAG (estimated average glucose)

(%) (mmol/L) (mg/dL)
5 5.4 (4.2–6.7) 97 (76–120)
6 7.0 (5.5–8.5) 126 (100–152)
7 8.6 (6.8–10.3) 154 (123–185)
8 10.2 (8.1–12.1) 183 (147–217)
9 11.8 (9.4–13.9) 212 (170–249)
10 13.4 (10.7–15.7) 240 (193–282)
11 14.9 (12.0–17.5) 269 (217–314)
12 16.5 (13.3–19.3) 298 (240–347)
Indications and use

Glycated hemoglobin testing is recommended for both (a) checking blood sugar control in people who might be
pre-diabetic and (b) monitoring blood sugar control in patients with more elevated levels, termed diabetes mellitus.
There is a significant proportion of people who are unaware of their elevated HbA1c level before they have blood
lab work.[22] For a single blood sample, it provides far more revealing information on glycemic behavior than a
fasting blood sugar value: Fasting blood sugar tests are crucial in making treatment decisions. The American
Diabetes Association guidelines are similar to others in advising that the glycosylated hemoglobin test be performed
at least two times a year in patients with diabetes that are meeting treatment goals (and that have stable glycemic
control) and quarterly in patients with diabetes whose therapy has changed or that are not meeting glycemic
goals.[23]
Glycated hemoglobin measurement is not appropriate where there has been a change in diet or treatment within 6
weeks. Likewise, the test assumes a normal red blood cell aging process and mix of hemoglobin subtypes
(predominantly HbA in normal adults). Hence, people with recent blood loss, hemolytic anemia, or genetic
differences in the hemoglobin molecule (hemoglobinopathy) such as sickle-cell disease and other conditions, as well
as those that have donated blood recently, are not suitable for this test.
Due to glycated hemoglobin's variability (as shown in the table above), additional measures should be checked in
patients at or near recommended goals. People with hemoglobin A1C values at 8.0% or less should be provided
additional testing to determine whether the HbA1c values are due to averaging out high blood glucose
(hyperglycemia) with low blood glucose (hypoglycemia) or the HbA1c is more reflective of an elevated blood
glucose that does not vary much throughout the day. Devices such as continuous blood glucose monitoring allow
people with diabetes to determine their blood glucose levels on a continuous basis, testing every few minutes.
Continuous use of blood glucose monitors is becoming more common, and the devices are covered by many health
insurance plans but not by Medicare. The supplies tend to be expensive, since the sensors must be changed at least
weekly. Another test that is useful in determining if HbA1c values are due to wide variations of blood glucose
throughout the day is 1,5 Anhydroglucitol, also known as GlycoMark. GlycoMark reflects only the times that the
person experiences hyperglycemia above 180 mg/dL over a two-week period.
Concentrations of hemoglobin A1 (HbA1) are increased, both in diabetic patients and in patients with renal failure,
when measured by ion-exchange chromatography. The thiobarbituric acid method (a chemical method specific for
the detection of glycation) shows that patients with renal failure have values for glycated hemoglobin similar to those
observed in normal subjects, suggesting that the high values in these patients are a result of binding of something
other than glucose to hemoglobin.[24]
In autoimmune hemolytic anemia, concentrations of hemoglobin A1 (HbA1) is undetectable. Administration of

prednisolone (PSL) will allow the HbA1 to be detected.[25] The alternative fructosamine test may be used in these
circumstances and it also reflects an average of blood glucose levels over the preceding 2 to 3 weeks.
All the major institutions like International Expert Committee Report, drawn from the International Diabetes
Federation (IDF), the European Association for the Study of diabetes (EASD), and the American Diabetes
Association (ADA), suggests the A1C level of 6.5% as a diagnostic level.[26] The Committee Report further states
that, when A1C testing cannot be done, the fasting and glucose tolerance tests be done.
Diagnosis of diabetes during pregnancy continues to require fasting and glucose tolerance measurements for
gestational diabetes, and not the glycated hemoglobin.
Modification by exercise training

Research done to identify the effect of two different kinds of training programs (combined aerobic and eccentric
resistance exercise program and aerobic exercise only) on the glycosylated hemoglobin levels of individuals with
T2DM found that the effect of combining resistance exercise with aerobic exercise improved the glucose control
more than just the aerobics alone. The average effect of the training programs included reductions of glycosylated
hemoglobin of 0.8 %, which was a result similar to that of long-term diet and drug or insulin therapy (which result in
a reduction of 0.6–0.8 %).[27]
Standardization & traceability

HbA1c is now standardized & traceable to IFCC methods HPLC-CE & HPLC-MS. A new unit (mmol/mol) is
used as part of this standardization.
See also
Diabetes mellitus
Hemoglobin
Advanced glycation end product
GlycoMark
References
1. ^ Executive Summary: Standards of Medical Care in Diabetes—2010
(http://care.diabetesjournals.org/content/33/Supplement_1/S4.extract) : Current criteria for the diagnosis of
diabetes. Diabetes Care January 2010 33:S4-S10; doi:10.2337/dc10-S004
2. ^ a b c Kilpatrick ES, Bloomgarden ZT, Zimmet PZ (2009). "Is haemoglobin A1c a step forward for
diagnosing diabetes?". BMJ 339: b4432. doi:10.1136/bmj.b4432
(http://dx.doi.org/10.1136%2Fbmj.b4432) . PMID 19903702
(http://www.ncbi.nlm.nih.gov/pubmed/19903702) .
3. ^ Larsen ML, Hørder M, Mogensen EF (1990). "Effect of long-term monitoring of glycosylated hemoglobin
levels in insulin-dependent diabetes mellitus". N. Engl. J. Med. 323 (15): 1021–5.
doi:10.1056/NEJM199010113231503 (http://dx.doi.org/10.1056%2FNEJM199010113231503) .
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4. ^ Huisman TH, Martis EA, Dozy A (1958). "Chromatography of hemoglobin types on
carboxymethylcellulose". J. Lab. Clin. Med. 52 (2): 312–27. PMID 13564011
5. ^ Bookchin RM, Gallop PM (1968). "Structure of hemoglobin A1c: nature of the N-terminal beta chain
blocking group". Biochem. Biophys. Res. Commun. 32 (1): 86–93. doi:10.1016/0006-291X(68)90430-0
(http://dx.doi.org/10.1016%2F0006-291X%2868%2990430-0) . PMID 4874776
6. ^ Rahbar S, Blumenfeld O, Ranney HM (1969). "Studies of an unusual hemoglobin in patients with diabetes
mellitus". Biochem. Biophys. Res. Commun. 36 (5): 838–43. doi:10.1016/0006-291X(69)90685-8
(http://dx.doi.org/10.1016%2F0006-291X%2869%2990685-8) . PMID 5808299
7. ^ Bunn HF, Haney DN, Gabbay KH, Gallop PM (1975). "Further identification of the nature and linkage of
the carbohydrate in hemoglobin A1c". Biochem. Biophys. Res. Commun. 67 (1): 103–9.
doi:10.1016/0006-291X(75)90289-2 (http://dx.doi.org/10.1016%2F0006-291X%2875%2990289-2) .
8. ^ Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976). "Correlation of glucose
regulation and hemoglobin AIc in diabetes mellitus". N. Engl. J. Med. 295 (8): 417–20.
doi:10.1056/NEJM197608192950804 (http://dx.doi.org/10.1056%2FNEJM197608192950804) .
9. ^ "Hemoglobin A1c Fact Sheet" (http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm) .
Michigan Diabetes Research & Training Center.
http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm. Retrieved 2007-12-26.
10. ^ Executive Summary: Standards of Medical Care in Diabetes—2010
(http://care.diabetesjournals.org/content/33/Supplement_1/S4.extract) : Current criteria for the diagnosis of
diabetes. Diabetes Care January 2010 33:S4-S10; doi:10.2337/dc10-S004
11. ^ Developing Point of care HbA1c tests for Diabetes monitoring
(http://www.devicelink.com/ivdt/archive/08/07/009.html) , Barry Plant, Originally Published IVDT
July/August 2008
12. ^ Geistanger A, Arends S, Berding C, et al. (August 2008). "Statistical methods for monitoring the
relationship between the IFCC reference measurement procedure for hemoglobin A1c and the designated
comparison methods in the United States, Japan, and Sweden". Clin. Chem. 54 (8): 1379–85.
doi:10.1373/clinchem.2008.103556 (http://dx.doi.org/10.1373%2Fclinchem.2008.103556) .
13. ^ Manley S, John WG, Marshall S (July 2004). "Introduction of IFCC reference method for calibration of
HbA: implications for clinical care". Diabet. Med. 21 (7): 673–6. doi:10.1111/j.1464-5491.2004.01311.x
(http://dx.doi.org/10.1111%2Fj.1464-5491.2004.01311.x) . PMID 15209757
14. ^ "Standardisation of the reference method for the measurement of HbA1c to improve diabetes care"
(http://www.acb.org.uk/docs/hba1c.pdf) (PDF). The Association for Clinical Biochemistry and Diabetss
UK. April 2008. http://www.acb.org.uk/docs/hba1c.pdf. Retrieved 2009-07-02.
15. ^ "All Change For HbA1c" (http://elearn-uhsm.co.uk/pathhandbook/Pathways_May_09.pdf) (PDF).
University Hospital of South Manchester. http://elearn-uhsm.co.uk/pathhandbook/Pathways_May_09.pdf.
Retrieved 2009-07-02.
16. ^ "HbA1c Standardisation For Laboratory Professionals"
(http://www.diabetes.org.uk/upload/Professionals/Key%20leaflets/53130HbA1cLableaflet.pdf) (PDF).
Diabetes UK.
http://www.diabetes.org.uk/upload/Professionals/Key%20leaflets/53130HbA1cLableaflet.pdf. Retrieved
2009-07-02.
17. ^ a b Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ (2008). "Translating the A1C assay
into estimated average glucose values." (http://care.diabetesjournals.org/content/31/8/1473.full) . Diabetes
Care 31 (8): 1473–8. doi:10.2337/dc08-0545 (http://dx.doi.org/10.2337%2Fdc08-0545) .
PMID 18540046 (http://www.ncbi.nlm.nih.gov/pubmed/18540046) . PMC 2742903
(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=2742903) .
http://care.diabetesjournals.org/content/31/8/1473.full.
18. ^ "Hemoglobin A1c Test" (http://www.medicinenet.com/hemoglobin_a1c_test/article.htm) .
MedicineNet.com. http://www.medicinenet.com/hemoglobin_a1c_test/article.htm. Retrieved 2007-12-26.
19. ^ "Executive Summary: Standards of medical care in diabetes—2009". Diabetes Care 32: S6–S12. 2009.
doi:10.2337/dc09-S006 (http://dx.doi.org/10.2337%2Fdc09-S006) .
20. ^ Lehman R, Krumholz HM (2009). "Tight control of blood glucose in long standing type 2 diabetes". Brit
Med J 338: b800. doi:10.1136/bmj.b800 (http://dx.doi.org/10.1136%2Fbmj.b800) .
21. ^ doi:10.1016/S0140-6736(09)61969-3 (http://dx.doi.org/10.1016%2FS0140-6736%2809%2961969-3)
22. ^ Walid MS, Newman BF, Yelverton JC, Nutter JP, Ajjan M, Robinson JS Jr (2009). "Prevalence of
previously unknown elevation of glycosylated hemoglobin (HbA1c) in spine surgery patients and impact on
length of stay and total cost". J Hosp Med 5 (1): NA. doi:10.1002/jhm.541
(http://dx.doi.org/10.1002%2Fjhm.541) . PMID 19753643
23. ^ American Diabetes Association (2007). "Standards of medical care in diabetes--2007". Diabetes Care
30 (Suppl 1): S4–S41. doi:10.2337/dc07-S004 (http://dx.doi.org/10.2337%2Fdc07-S004) .
24. ^ "Glycated Hemoglobin in Uremic Patients as Measured by Affinity and Ion-Exchange Chromatography"
(http://www.clinchem.org/cgi/reprint/30/3/485.pdf) . clinchem.com.
http://www.clinchem.org/cgi/reprint/30/3/485.pdf. Retrieved 2009-08-31.
25. ^ "Undetectable Glycated Hemoglobin in Autoimmune Hemolytic Anemia" (http://repository.oai.yamaguchi-
u.ac.jp/yunoca/A02/A020052000103.pdf) . repository.oai.yamaguchi-u.ac.jp.
http://repository.oai.yamaguchi-u.ac.jp/yunoca/A02/A020052000103.pdf. Retrieved 2009-08-31.
26. ^ The International Expert Committee (2009). "International expert committee report on the role of the A1C
assay in the diagnosis of diabetes" (http://www.pubmedcentral.nih.gov/articlerender.fcgi?
tool=pmcentrez&artid=2699715) . Diabetes Care 32 (7): 1327–1334. doi:10.2337/dc09-9033
(http://dx.doi.org/10.2337%2Fdc09-9033) . PMID 19502545
27. ^ Marcus et al. "Comparison of Combined Aerobic and High-Force Eccentric Resistance Exercise With
Aerobic Exercise Only for People With Type 2 Diabetes Mellitus." Physical Therapy 88.11 (2008): p1345-
1354. EBSCO. Web. 12 Oct. 2009.
External links
National Diabetes Information Clearinghouse (http://diabetes.niddk.nih.gov/)
American Diabetes Association Standards of Medical Care 2007
(http://care.diabetesjournals.org/cgi/content/full/30/suppl_1/S4)
Hemoglobin A1c Test (http://www.medicinenet.com/hemoglobin_a1c_test/article.htm)
MDRTC Hemoglobin A1C Fact Sheet (http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm)
Simple Online A1c Calculator (http://www.pace-med-apps.com/a1ccalc.htm)
Metrika: A1C test for professionals and consumers. (http://www.metrika.com/)
The Appraise Home A1c Kit is the easy, 'at home' accurate and affordable way to reduce risk.
(http://www.appraisetests.com/)
Developing Point of care HbA1c tests for Diabetes monitoring. Aug 2008
(http://www.devicelink.com/ivdt/archive/08/07/009.html) Discusses different test methods
HbA1c to eAG (estimated Average Glucose) calculator
(http://professional.diabetes.org/GlucoseCalculator.aspx) in mmol/l and mg/dl including resources. American
Diabetes Association
What is HbA1c? (http://www.diabetes.co.uk/what-is-hba1c.html)
Retrieved from "http://en.wikipedia.org/wiki/Glycated_hemoglobin"
Categories: Blood tests | Diabetes-related tests | Diabetes | Blood proteins | Hemoproteins
This page was last modified on 11 December 2010 at 17:30.

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Glycated Hemoglobin

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Formatos disponibles

12/22/2010 Glycated hemoglobin - Wikipedia, the f…

Point of care (e.g. doctor's surgery) devices use:

Switch to IFCC units

DCCT- HbA1c IFCC-HbA1c

eAG(mg/dl) = 28.7 × A1C − 46.7

HbA1c eAG (estimated average glucose)

Indications and use

In autoimmune hemolytic anemia, concentrations of hemoglobin A1 (HbA1) is undetectable. Administration of

Modification by exercise training

Standardization & traceability

This page was last modified on 11 December 2010 at 17:30.

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