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Screening and

Diagnosis and the


Role of Early
Pharmacotherapy
Learning Objectives

Recognize the importance of screen high risk


patients for the early identification of pre-
diabetes or diabetes
Identify best practices for diagnosing a patient
with T2DM
Utilize treatment algorithms to guide selection
of appropriate therapeutic interventions
T2DM Prevalence in Indonesia: 5.7%

73.7% were undiagnosed

73.7 26.3 26.3

Undiagnosed Diagnosed

Indonesian National Health Survey 2007.


Association between hyperglycaemia
and CVD starts long before the onset of
type 2 diabetes

Prediabetes Diabetes tipe-2


Plasma glucose (mmol/L)

30

25 Type 2
diabetes
20

15 Micro-
Undiagnosed vascular
10
diabetes disease

5 IGT
Normal
0

Macro-
vascular
Up to 10 years disease

NHANES: National Health and Nutrition Examination Survey


www.cdc.gov/nchs/products/elec_prods/subject/nhanesii.htm
Janka HU. Fortschr Med 1992;110:63741
NHANES reveals the under-management
of diabetes (1999-2000 population with DM)

Mean HbA1c value was 7.8%


37% had an HbA1c value <7.0%
26% had an HbA1c value of 7.08.0%
37% had an HbA1c value >8.0
Saydah S, et al. JAMA 291:33542, 2004

Only 22-46% of diabetes patients met the LDL


cholesterol goal
Only 29-33% met the blood pressure goal
Far fewer, 2-10%, met the combined ADA goals for
glycemia, lipids, and blood pressure
Davidson, Curr Diabetes Rev 3:280-286, 2007
Complication at the Time of Diagnosis

9% neuropathy
20% retinopathy
Diagnosed DM = 1,5% 8% nephropathy
50% heart & blood
Undiagnosed DM = 4,2% vessel
Total DM = 5,7%
IGT = 10,2 %
Early detection and diagnosis

Prediabetes Type-2 DM

Early Early
Plasma glucose (mmol/L)

30
detection of detection
25 Risk Factors of newly Type 2
Healthy & newly DM DM (?) diabetes
20
lifestyle
15 promotion Undiagnosed
Micro-
vascular
10
diabetes disease

5 IGT
Normal
0

Macro-
vascular
disease
Up to 10 years

NHANES: National Health and Nutrition Examination Survey


www.cdc.gov/nchs/products/elec_prods/subject/nhanesii.htm
Janka HU. Fortschr Med 1992;110:63741
Early Detection of Type-2 Diabetes
Mellitus

TREAT AS NEEDED
Group with
Screening

RISK Factors Diabetes


Group without Mellitus
RISK Factors
RISK SCORING

Do:
Diagnosis - DM
- OGTT
Criteria - Pre DM
- HbA1 measurement
ADA: Risk Test for T2DM

http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/
Screening

Screening is recommended to identify people


with previously undiagnosed diabetes so that
they get appropriate care

Observational studies demonstrate that


people diagnosed as a result of screening
have better outcomes than those presenting
spontaneously with diabetes 1

Pramono LA et al. Acta Med Indones 2010;42(4):216-23.


Medical Management of Type 2 Diabetes, 7th Edition. American Diabetes Association, 2012.
Who Should Be Screened?

In all adults who are overweight


(BMI 25 kg/m2; Asia: 23 kg/m2) and have
additional risk factors

In the absence of these criteria, testing for


diabetes should begin at age 45 years

If results are normal, testing should be repeated at


least at 3-year intervals, with consideration of more
frequent testing depending on initial results and
risk status

ADA, Medical Management of Type 2 Diabetes, 7th Edition, 2012.


Screening

Screening is conducted on those who are


at risk for diabetes but show no symptoms
(see risk factors next slide)
Screening seeks to capture undiagnosed
T2DM or pre-diabetes so it can be managed
earlier/ more appropriately
Mass screening is not recommended due
to cost

PERKENI Consensus Guidelines, 2011.


High Risk Screening

High-risk population at age < 30 years old

Family history of Increase of TG/decrease


diabetes of HDL or both
Cardiovascular History of gestational
abnormalities diabetes
Overweight History of delivering
Sedentary life infant > 4000 g
History of IFG or IGT Polycystic ovary
Hypertension syndrome

PERKENI Consensus Guidelines, 2011.


Obesity in Indonesia
BHS, 2007 and BHS 2010 (Ministry of Health)

2007 2010
%
Toddlers 12.2 14.0
6-12 years old female 6.4 7.7
6-12 years old male 9.5 10.7
15-18 years old female 23.8 26.9
15-18 years old male 13.9 16.3

>18 years old 10.3 11.7


During 3 years the obesity prevalences in toddlers increased from
12.2% to 14.0% as well as in 6-12 years group from 7.9 % to 9.2%
(total).
In adult 18 years the obesity prevalences was increased by 1.4%
(from 10.3% to 11.7%) while overweight among age group > 18 years
increased from 8.8% to 10.7%.
BMI and DM (BHS, 2007)
Indonesian Ministry of Health

9.1%
7.3%
Prevalence of DM

4.4%
3.7%

BMI <18 18 - 22 23 - 26 >27


Diagnosis
Algorithm of T2DM Diagnosis
Diabetes Symptoms
Diabetes Classic Diabetes Classic
Symptoms (+) GDP Symptoms (-)
GDS
FPG 126 < 126 126 100-125 < 100

RBG > 200 < 200 > 200 140-199 < 140

FBG and PPG


OGTT
2 hour BG
FPG 126 < 126

RBG > 200 < 200 > 200 140-199 < 140

Diabetes Mellitus IGT IFG Normal

Evaluation of Nutritional Status Education


Evaluation Diabetic Complications Dietary Planning
Evaluation Dietary Need and Dietary Planning Physical Exercise
Achieving Ideal Body Weight

FBG (Fasting Blood Glucose) IGT (Impaired Glucose Tolerance) PERKENI Consensus Guidelines, 2011.
RBG (Random Blood Glucose) IFG (Impaired Fasting Glucose)
Diagnostic Criteria for Prediabetes

Pre-Diabetes Diabetes
100 < FBG < 126 > 126
140 < PPG < 200 > 200
5.7 < A1C < 6.5%* > 6.5%*

* A1C not yet recommended in Indonesia

PERKENI Consensus Guidelines, 2011.


Early Management
Management

Periodic
Blood
Early Life Style Pharmacology Glucose
Detection Changes Therapy and Risk
Factor
Monitoring

High-risk population at Medical Nutritional


<30-year old Therapy Not yet
Family history of DM Hypertension
Physical activity recommended
Cardiovascular disorder Dyslipidemia
Weight reduction
Overweight Physical
Sedentary life style health
If overweight,
Known IFG or IGT Body weight
reduce body
Hypertension control
weight by 5-10%
Elevated Triglyseride, Physical exercise
low HDL or both for 30 minutes,
History of Gestational 5x/week
DM
History of give birth >
4000g
PCOS

2-hour OGTT is the most


sensitive method for early
detection and a recommended
screening test procedure PERKENI Guidelines. Diabetes Mellitus National Clinical Practice Guidelines. 2011
Risk Factors

Nonmodifiable Modifiable
Age Overweight
Race/Ethnicity Abnormal lipid
metabolism
Gender
Inflammation,
Family history hypercoagulation
Hypertension
Smoking
Physical inactivity
Unhealthy diet
Insulin resistance
Management
Lifestyle Modification

Dietary intervention
Reduce intake by 5001000 kcal/day from total
daily intake

Increased physical activity


Moderate activity 30-45 mins/day, 3-5 times/week
Overweight and obese individuals: Moderate
activity 45-60 mins/day 5 times/week .

Purnamasari D et al. Identification, Evaluation and treatment of overweight and obesity in adults: Clinical
Practice Guidelines of the Obesity Clinic, Wellness Cluster Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Risk Management:
Weight Loss Recommendations

Weight loss therapy is recommended for:


BMI 25 kg/m2
BMI 23-24.9 kg/m2 + 2 risk factors
High-risk waist circumference + 2 risk factors
(comorbidities)

Weight management programs should include


lifestyle modification and behavioral
management

Purnamasari D et al. Identification, Evaluation and treatment of overweight and obesity in adults: Clinical
Practice Guidelines of the Obesity Clinic, Wellness Cluster Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Medical Nutrition Therapy (MNT)

An essential component of comprehensive care


and management

Often contributes to A1C of 1-2% within 6-12


weeks of beginning MNT

Lowers BP, improves lipid profile and


improves QOL
BP=blood pressure
QOL=quality of life

Daly A, Power MA. Medical Nutrition Therapy. Diabetes Mellitus and Related Disorders; Medical Management of Type
2 Diabetes, 7th Edition. American Diabetes Association, 2012.
Exercise in the
Prevention of T2DM

Characteristics &
Study Intervention Results
Duration
577 people 67.7% cumulative
>25 years incidence in the
Da Quing control group
Study Diet +
(China) Random selection 43.8% (reduction of 31%)
Exercise
2007 from clinics 41.1% (reduction of 46%)
46% (reduction of 42%)
6 years follow-up
522 people,
Finnish 40-64 years
Diabetes
BMI> 25 58% decreased
Prevention Diet +
incidence in the
Study Random selection Exercise
diet + exercise group
(Finland) by people
2001
3.2 years follow-up
Pan, Li, Hu et al., 1997
Tuomilehto, Lindstrom, Eriksson, et al., 2001
Exercise in the
Prevention of T2DM (contd)

Characteristics &
Study Intervention Results
Duration
31% decreased
3234 persons= >25 years
incidence of diabetes
Diabetes Placebo
in the metformin
Prevention BMI= >22 (Asian people),
group
Programme >24 (other groups) Metformin
(USA)
2002 58% decreased
Random selection 2.8 Diet + Exercise
incidence in the diet
years follow-up
+ exercise group

Diabetes Prevention Program, 2002


Relative Effectiveness of
Interventions in Diabetes Prevention
40
Placebo
Cumulative Incidence

30
Metformin
of Diabetes (%)

20 Lifestyle

10

0
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
Years

Knowler WC, et al. NEJM. 2002;346:393-403.


Prediabetes, management

Target lifestyle changes and use adjunct


pharmacologic treatment for specific priorities
eg, hypertension1

The decision to start pharmacologic treatment


must be based on a risk-benefit analysis2
Metformin and acarbose: safe & effective
Thiazolidinedione (TZD): associated risk of
congestive heart failure and fracture should be
given attention.
1.Saewonder & Pramono. Prevalence, characteristics, and predictors of pre-diabetes in Indonesia. Med J Indones 2011; 20: 283-94.
2. Buku Panduan Pengelolaan dan Pencegahan Prediabetes. 2010 (Guideline book on Management and Prevention of Prediabetes)
Study
Diet
Hazard ratio (95% CI) Meta-analysis
Da Qing 1997w22 0.64 (0.41 to 0.99) Effects of lifestyle
Jarrett 1979w22 0.85 (0.40 to 1.81)
Wein 1999w35 0.63 (0.35 to 1.14)
intervention on risk of
developing type 2 diabetes
Pooled effect 0.67 (0.49 to 0.92)

Exercise
Da Qing 1997w22 0.53 (0.34 to 0.82)
Tao 2004w21 0.30 (0.10 to 0.93)

Pooled effect 0.49 (0.32 to 0.74)

Diet and exerise


Da Qing 1997w22 0.61 (0.39 to 0.95)
DPP 2002w23 0.42 (0.34 to 0.52)
DPS 2003w25 0.40 (0.26 to 0.61)
Fang 2004w19 0.75 (0.35 to 1.60)
IDDP 2006w39 0.62 (0.42 to 0.92)
Kosaka 2005w27 0.29 (0.09 to 0.94)
Liao 2002w29 0.52 (0.05 to 5.69)

Pooled effect 0.49 (0.40 to 0.59)

Overallpooled effect 0.51 (0.44 to 0.60)


Gillies GL et al. Downloaded from bmj.com on 31
0 1 2 3
Favours Favours October 2008
intervention control
Study Treatment
Oral diabetes drugs Hazard ratio (95% CI)
Fang 2004w19 Acarbose 0.27 (0.09 to 0.79
Pan 2003w31 Acarbose 0.60 (0.24 to 1.53) Meta-analyses
STOP-NIDDM 2002w33 Acarbose 0.75 (0.63 to 0.90)
Fang 2004w19 Flumamine 0.43 (0.16 to 1.14) Effect of
Eriksson 2006w38 Glipizide 0.18 (0.02 to 1.50) pharmacological
DPP 202w23 Metformin 0.69 (0.57 to 0.84) and herbal
IDDP 2006w39 Metformin 0.65 (0.44 to 0.96)
Li 1999w30 Metformin 0.49 (0.12 to 1.95)
interventions on
Jarrett 1979w2 Phenformin 1.01 (0.48 to 2.15) risk of developing
type 2 diabetes
Pooled effect 0.71 (0.62 to 0.79)

Anti-obesity drug
Heymsfield 2000w28 Orlistat 0.39 ()0.19 to 0.78
XENDOS 2004w37 Orlistat 0.48 (0.26 to 0.88)

Pooled effect 0.44 (0.28 to 0.69)

Herbal
Fan 2004w20 Jiangtang bushen recipe 0.32 (0.03 to 3.07)

0 1 2 3 Gillies GL et al.
Favours Favours Downloaded from bmj.com
intervention control on 31 October
Treatment based on HbA1c Level
<7% 7-8% 8-9% >9% 9-10% >10%

Lifestyle Lifestyle
Modification Modification

+ Lifestyle
Modification
Monotherapy
+ Lifestyle
Met, SU, AGI,
Glinid, TZD, Modification
2 OADs
DPP-IV Combination +
Met, SU, AGI,
Glinid, TZD, 3 OADs Lifestyle
DPP-IV Combination Modification
Met, SU, AGI,
+
Glinid, TZD,
DPP-IV 2 OADs
Combination
Notes : Met, SU, AGI,
Fail : not achieving A1c target Glinid, TZD
Lifestyle
<7% after 2-3 months of + Modification
treatment.
(A1c = average blood glucose Basal Insulin +
conversion, ADA 2010) Intensive
Insulin
T2DM Antihyperglycemic Therapy: General Recommendations
Healthy eating, weight control, increased physical activity

Initial Drug Metformin


Monotherapy Metformin
Efficacy (HbA1c) High
High
Hypoglycemia Low
Lowrisk
risk

Weight Neutral // loss


Neutral loss

Side effects GIGI/ /lactic


lactic acidosis
acid
Low
Costs Low

Diabetes Care. Diabetologia 19 June 2012


T2DM Antihyperglycemic Therapy: General Recommendations
Healthy eating, weight control, increased physical activity
Initial Drug Initial Drug Monotherapy Metformin

Monotherapy Efficacy (HbA1c) High

Hypoglycemia Low risk

Weight Neutral / loss

Side effects GI / lactic acid

Costs Low

If needed to reach individualized HbA1c target after -3 months, proceed to 2-


drug combination (order not meant to denote any specific preference)

Two drug Sulfonylurea Thiazolidine- DPP-4 GLP-1 Insulin


combinations dione Inhibitor receptor (usually
agonist basal)
Efficacy High High Intermediate HIgh Highest
(HbA1c)
Hypoglycemia Moderate risk Low risk Low risk Low risk High risk
Weight Gain Gain Neutral Loss Gain
Side effects Hypoglycemia Edema, HF, Rare GI Hypo-
fxs glycemia
Costs Low High High High Variable

Diabetes Care. Diabetologia 19 June 2012


T2DM Antihyperglycemic Therapy: General Recommendations
Healthy eating, weight control, increased physical activity
Initial Drug Initial Drug Monotherapy Metformin

Monotherapy Efficacy (HbA1c) High

Hypoglycemia Low risk

Weight Neutral / loss

Side effects GI / lactic acid

Costs Low

If needed to reach individualized HbA1c target after -3 months, proceed to 2-


drug combination (order not meant to denote any specific preference)

Two Drug Two drug combinations Sulfonylurea Thiazolidine-dione DPP-4 Inhibitor GLP-1 receptor Insulin (usually
agonist basal)
Combinations
Efficacy (HbA1c) High High Intermediate HIgh Highest

Hypoglycemia Moderate risk Low risk Low risk Low risk High risk

Weight Gain Gain Neutral Loss Gain

Side effects Hypoglycemia Edema, HF Rare GI Hypoglycemia

Costs Low High High High Variable

Sulfonylurea + Thiazolidine- DPP-4 GLP-1 Insulin


dione + Inhibitor + receptor (usually
Three Drug
agonist + basal)
Combinations
TZD SU SU SU TZD
Or DPP-4-i Or DPP-4-i Or TZD Or TZD Or DPP-4-i
Or GLP-1-RA Or GLP-1-RA Or Insulin Or Insulin Or GLP-1-RA
Or Insulin Or Insulin
Diabetes Care. Diabetologia 19 June 2012
T2DM Antihyperglycemic Therapy: General Recommendations
Healthy eating, weight control, increased physical activity
Initial Drug Monotherapy Metformin

Efficacy (HbA1c) High


Initial Drug Hypoglycemia Low risk
Monotherapy Weight Neutral / loss

Side effects GI / lactic acid

Costs Low

If needed to reach individualized HbA1c target after -3 months, proceed to 2-


drug combination (order not meant to denote any specific preference)

Two drug combinations Sulfonylurea Thiazolidine- DPP-4 Inhibitor GLP-1 Insulin (usually
dione receptor basal)
Two Drug agonist

Combinations Efficacy (HbA1c) High High Intermediate HIgh Highest

Hypoglycemia Moderate risk Low risk Low risk Low risk High risk

Weight Gain Gain Neutral Loss Gain

Side effects Hypoglycemia Edema, HF Rare GI Hypoglycemia

Costs Low High High High Variable

Sulfonylurea + Thiazolidine-dione + DPP-4 Inhibitor + GLP-1 receptor Insulin (usually


Three Drug agonist + basal)

Combinations TZD SU SU SU TZD

Or DPP-4-i Or DPP-4-i Or TZD Or TZD Or DPP-4-i

Or GLP-1-RA Or GLP-1-RA Or Insulin Or Insulin Or GLP-1-RA

Or Insulin Or Insulin

If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months,
proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents
More complex
insulin strategies Insulin (multiple daily doses)
Diabetes Care. Diabetologia 19 June 2012
Summary

Screening people with identified risk factors


provides early diagnosis and management of
pre-diabetes or diabetes
Diagnostic algorithms based on blood glucose
level allow for the differentiation of pre-diabetes
and diabetes
Treatment algorithms guide optimal therapy
based on disease severity (assessed via
laboratory measures)
Diagnostic Criteria for T2DM

Classic symptoms of diabetes + random


glucose plasma level 200 mg/dL
o Random glucose plasma level assesses
glucose plasma level a single time without
concern for schedule of last meal.
or
Classic symptoms of diabetes + Fasting
plasma glucose 126 mg/dL
o Fasting means no intake of food for a
minimum 8 hours.

PERKENI Consensus Guidelines, 2011.


Diagnostic Criteria for T2DM

or
2-h plasma glucose at glucose tolerance test
200 mg/dL
o Glucose tolerance test (WHO standard)
using 75 g anhydrous glucose diluted in
100 cc water.

PERKENI Consensus Guidelines, 2011.


Diabetes Classification

I. T1DM (-cell destruction, usually leading to


absolute insulin deficiency)
A. Immune mediated
B. Idiopathic

II. T2DM (may range from predominantly insulin


resistance with relative insulin deficiency to a
predominantly secretory defect with insulin
resistance)

ADA, Medical Management of Type 2 Diabetes, 7th Edition, 2012.


Diabetes Classification

III. Other specific types


a. Genetic defects of -cell function
b. Genetic defects in insulin action
c. Diseases of the exocrine pancreas
d. Endocrinopathies
e. Drug or chemical induced
f. Infections
g. Uncommon forms of immune-mediated diabetes

IV. Gestational diabetes mellitus

ADA, Medical Management of Type 2 Diabetes, 7th Edition, 2012.


Diagnostic Codes: Indonesia

ICID Code Description


1. E 10 IDDM
2. E 11 NIDDM
3. 10.5 IDDM with peripheral circulatory
complications/gangrene diabetic
4. E 11.5 NIDDM with peripheral circulatory
complications/gangrene diabetic
6. E 66 Obesity
IDDM = Insulin Dependent Diabetes Mellitus
NIDDM = Non Insulin Dependent Diabetes

Ministry of Health, Republic of Indonesia, 2012.


Treatment Algorithms
PERKENI: Early Detection

High risk population at the age


< 30 years old
Family history of diabetes Hypertension
Cardiovascular abnormalities Increase of TG/Decrease of HDL or both
Overweight History of Gestational Diabetes
Sedentary life History of delivering infant > 4000g
History of IFG or IGT PCOS

OGTT is the most sensitive method for early detection


and the recommended screening tool
In the US Population, Screening for T2DM is Cost
Effective When Started Between Ages 30-60

Screening Strategy QALYs Added Cost per QALY (USD)


30 years, every 3 years 171 $10 512
45 years, every year 149 $15 509
45 years, every 3 years 128 $9731
45 years, every 5 years 114 $9786
60 years, every 3 years 93 $25 738
Hypertension diagnosis, every years 78 $6287
Hypertension diagnosis, every 5 years 77 $6490
Maximum screening 194 $40 778

QALY=Quality Adjusted Life Years

Kahn RA et al. Lancet 2010;375:1365-74.