prediabetes_oke_idi lmgn.ppt

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dr. Abdur Rohman, SpPD

Prediabetes:

Treat or not to treat,

an Integrated Approach



Diagnostic Criteria for T2DM

• Classic symptoms of diabetes + random

glucose plasma level ≥ 200 mg/dLo 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/dLo 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) using75 g anhydrous glucose diluted in 100 cc

water.




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




The global burden

366 million people have diabetes in 2011; by 2030 this will have risen to 552

million

The number of people with type 2 diabetes is increasing in every country

80% of people with diabetes live in low-and middle-income countries

The greatest number of people with diabetes are between 40 to 59 years of

age

183 million people (50%) with diabetes are undiagnosed

Diabetes caused 4.6 million deaths in 2011

Diabetes caused at least USD 465 billion dollars in healthcare expenditures in

2011; 11% of total healthcare expenditures in adults (20-79 years)

78,000 children develop type 1 diabetes every year



Diabetes is an Increasing Healthcare

Epidemic Throughout the World

Global Projections for the Number of People with Diabetes(20 –79 age group), 2007 –2025 (millions)

Africa

Eastern Mediterraneanand Middle East

Europe

North America

South and Central America

South-East Asia

Western Pacific

28.3

40.5

+43%

16.2

32.7

+102%

10.418.7

+80%

24.5

44.5

+81%

53.2

64.1

+21%

67.0

99.4

+48%

46.5

80.3+73%

IDF. Diabetes Atlas 3rd Edition – 2006

Worldwide:246 million people in 2007

380 million projected for 202555% increase



Increasing DM Prevalence in Indonesia

1985 2007

WHO, Study Group 1985

RISKESDAS, 2007

5.7%

1.7%

NATIONAL



Number of People with Diabetes (20-79 years),

2010 and 2030

2010 2030

Country/Territory Millions Country/Territory Millions

1 India 50.8 1 India 87.0

2 China 43.2 2 China 62.6

3 USA 26.8 3 USA 36.0

4 Russian Federation 9.6 4 Pakistan 13.8

5 Brazil 7.6 5 Brazil 12.7

6 Germany 7.5 6 Indonesia 12.0

7 Pakistan 7.1 7 Mexico 11.9

8 Japan 7.1 8 Bangladesh 10.4

9 Indonesia 7.0 9 Russian Federation 10.3

10 Mexico 6.8 10 Egypt 8.6



Indonesia: Distribution of DM (%)

Note: Riskesdas is Riset Kesehatan Dasar (Basic Health Research)

< 4.2 4.2 – 6.8 > 6.8

DISTRIBUTION OF

DIABETES MELLITUS (%)

Riskesdas, 2007

DM (%)



Prevalence of DM in Indonesia

1.7%

Papua

11.1%

Maluku Utara

RISKESDAS, 2007

National

6.2%

Lampung

5.7%



DM Prevalence by Provinces in Indonesia

(Riskesdas 2007)



Impaired Glucose Tolerance (IGT)

• 10.2% of the urban Indonesian population

has impaired glucose tolerance

Mihardja et al. Prevalence and determinants of diabetes mellitus and impaired glucose tolerance in Indonesia.

Acta Med Indones-Indones J Intern Med. 2009



Indonesia: Distribution of IGT (%)

Note: Riskesdas is Riset Kesehatan Dasar (Basic Health Research)

< 8.4 8.4 - 13.1 > 13.1

DISTRIBUTION OF IMPAIRED

GLUCOSE TOLERANCE (%)

Riskesdas, 2007

IGT (%)



IGT Prevalence by Provinces in

Indonesia (Riskesdas 2007)



Predictive Factors

• Undiagnosed

diabetes:

– Age

–Obesity –Central obesity

–Hypertension

–Smoking

• Pre-diabetes:

– Male

– Older

– High socioeconomic

status

– Low education level

– Hypertension – Obesity

– Central obesity

– SmokingNational Health Survey 200724417 subjects from 33 provinces in Indonesia.



Attributable Risk of Several Predictive

Factors of Pre-diabetes in Indonesia

23%

47.30%

56.50%

23%

16.70%

44.40%

0%

10%

20%

30%

40%

50%

60%

Obesity Central obesity Hypertension Physicalinactivity

High risk diet(less fruits and

vegetables)

Smoking habit

Priority:• Decrease blood pressure (AR 56.5%),

• Reduce waist circumference (AR 47.3%)

• Stop smoking (AR 44.4%).

National Health Survey 200724417 subjects from 33 provinces in Indonesia.



Diabetic Complications

IDMPS Indonesia0

10

20

30

40

50

60

33.4

54

26.5

0.5

8.7

1.3

7.45.3

2.75.3

10.9

Retinopathy

Neuropathy

Proteinuria

Dialysis

Foot Ulcer

Amputation

Angina

MCI

Heart Failure

Stroke

PAD

Microangiopathy >> Macroangiopathy



Prevalences of Obesity (BMI) in Indonesia

(Basic Health Research - 2007)

Recruited 19.114 person-across 438 districts (percentage)

(Indonesia Ministry of Health Affair – 2007)



Prevalences of IGT and DM in Indonesia(Basic Health Research – 2007)

Recruited 24.417 person – across 438 districts

(Indonesia Ministry of Health Affair – 2007)

(percentage)



Prediabetes

People who know they

have diabetes

People who don’t

know they have

diabetes

Indonesian basic

health research

(Riskesdas)

Diagnosed DM = 1,5%Undiagnosed DM = 4,2%

Total DM = 5,7%

IGT = 10,2 %



Complication at the Time of Diagnosis

9% neuropathy

20% retinopathy

8% nephropathy

50% heart & blood

vessel

Indonesian basic

health research

(Riskesdas)

Diagnosed DM = 1,5%Undiagnosed DM = 4,2%

Total DM = 5,7%

IGT = 10,2 %

People who don’t

know they have

diabetes



DECODE PPHG i b tt



DECODE: PPHG is better

correlated with cardiovascular and

all-cause mortality than FPG

FPG (mmol/l)

H a z a r d r

a t i o

DECODE Study Group. Lancet 1999;354:617-21.PPHG : Post Prandial Hyperglycemia, FPG : Fasting Plasma Glucose



DECODA

2hPG (mmol/L)

Adjusted for FPG criteria

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

M u l t i v a r i a t e h a z a r d r a t i o

<6.1 6.1 –6.9 ≥7.0 <7.8 7.8 –11.0 ≥11.1

trendp=0.81

trendp=0.83

trendp<0.001

trendp<0.001

FPG (mmol/L)

Adjusted for 2hPG criteria

All-cause mortality CVD mortality

Nagamaki et al Diabetologia 2004; 47:385

Detection of glucose perturbations Added prognostic information of postprandial glycaemia



“Asian Phenotype” Type 2 Diabetes

• Primary phenomenon : reduced beta-cell function1

• Postprandial hyperglycaemia key diagnostic finding1

• Fasting glucose normal1

• Postprandial glucose central to management

1. DECODA Study Group. Cardiovascular risk profile assessment in glucose-tolerant Asian individuals—an evaluation of the World Health Organization two-step strategy: the DECODA study. Diabet Med2002;19:549-57.



Postprandial Hyperglycaemia – “Early Warning” for

Diabetes

Impaired glucose tolerance(IGT) appears first

HbA 1c & fasting glucose arestill normal at this stage1,2

Increased risk of CVcomplications begins beforeovert diabetes develops.3

=> Measurement of postprandial glucose allowsearly identification of at-risk

individuals

Increased risk of CV complications beginsin the non-diabetic range of glucose disregulation1

R e l a t i v e r i s k

Plasma glucose level

1.0

CVD

DiabetesGlucose

intoleranceNormal

Microvascular

1. Gerstein HC. Glucose: a continuous risk factor for cardiovascular disease. Diabet Med 1997;14(Suppl 3):S25-31.

2. Reaven GM et al. Does Hyperglycaemia or hyperinsulinemia characterize the patient with chemical diabetes?Lancet 1972;I;1247-1249.

3. Little RR et al. Relationship of glycosylated hemoglobin to oral glucose tolerance: implications for diabetes

screening. Diabetes 1988;37:60-64.



Natural History of Type 2 Diabetes

International Diabetes Centre, Minneapolis, MN.

Years of diabetes

–20 –10 0 10 20 30

Post-meal glucose

Fasting glucose

Insulin resistance

Insulin level

120

100

P l a

s m a g l u c o s e

( m g / d L )

R e l a t i v eb -

c e l l

f u n c t i o n ( % )

Obesity Impaired

glucosetolerance

Diabetes Uncontrolled

hyperglycaemia



Haller H. Diab Res Clin Pract 1998;40(Suppl.):43 –9.

Steady

state

Metabolic

effects

Vascular

effects

Pre-diabetes

ß- cell dysfunction Type 2 diabetes

Meal

Hyper-glycaemia

Stress tovascular walls

Consequences of high postprandial plasma glucose levels are moredangerous than the total glucose impact (HbA1c)

Atherosclerosis and

late complications

Endothelial

dysfunction

Normal HbA1c

elevated HbA1c

DETERMINED



DETERMINED

FACTORS

Age 30 or above for

Populations at High Risk:

• Family history of diabetes

• Cardiovascular disease

• Overweight

• Sedentary lifestyle

• Previously identified IGT or IFG

• Hypertension

• Elevated triglycerides low HDL, or both• History of gestational diabetes

• Delivery of a baby weighing > 4kg

• Severe psychiatric illness

RISK

STRATIFICATIONS

Scoring:

>7:

7-11:

12-14:

15-20:

>20:

Low, 1/100 to develop DM

Increase, 1/25 to develop DM

Moderate, 1/6 to develop DM

High, 1/3 to develop DM

Very High, 1/2 to develop DM

FOCUSGROUP:HIGH RISK

VERY RISK

IGT

IFG

CVD

GESTATIONAL DM

OGTTNORMAL

IFG

IGT

DM

ADVICE

INTERVENTION

TREAT TO TARGET

MANAGEMENT



INTERVENTION

Lifestyle (0,5-1 kg/week)

5-7% reduction in body weight

(if overweight)

Exercise (Physical Fitness)

30 min, 5 times/week

(equivalence of brisk walking)

Pharmacologic

- AGI (e.g. Acarbose)*

- Metformin

- Orlistat

- T2D

* Glucobay (acarbose) is the first and only OAD approved to treat Prediabetes in Indonesia

Road Map to PREVENT Type 2 Diabetes



Road Map to PREVENT Type 2 Diabetes

Early

Identification Lifestyle

Modification Pharmacologic Persistent

Monitoring of

Glucose andRisk Reduction

Measures

Intervention

Age 30 or above for

Populations at High Risk:

FPG or 2-h OGTT is the

recommended screening procedure

• Medical Nutrition

Therapy (MNT)

• Physical Fitness

Program

• Weight Loss

• 5-7% reduction in body

weight (if overweight)

• 30 minutes exercise, 5

times per week at theequivalence of brisk

walking

• AGI (e.g. acarbose)*

• Metformin

• Orlistat

• TZD**

*Shown to be effective in delaying the onset of

type 2 diabetes in clinical studies

** A recent meta-analysis suggests a possible

link of rosiglitazone to cardiovascular events;

other studies do not confirm or exclude this risk.

The FDA has stated “In their entirety, the available data on

the risk of myocardial infarction are inconclusive.”

• Hypertension

• Dyslipidemia

• Physical Fitness

• Weight Control

• Family history of diabetes

• Cardiovascular disease• Overweight

• Sedentary lifestyle

• Latino/Hispanic, African

American, Asian American,

Native American, or

Pacific Islander

• Previously identified IGT

or IFG

• Hypertension

• Elevated triglycerides,

low HDL, or both• History of gestational

diabetes

• Delivery of a baby weighing

more than 9 lbs

• Severe psychiatric illness

ACE/AACE Diabetes Road Map Task Force

Paul S. Jellinger, MD, MACE, Co-Chair

Jaime A. Davidson, MD, FACE, Co-Chair

Lawrence Blonde, MD, FACP, FACE

Daniel Einhorn, MD, FACP, FACE

George Grunberger, MD, FACP, FACE

Yehuda Handelsman, MD, FACP, FACE

Richard Hellman, MD, FACP, FACE

Harold Lebovitz, MD, FACE

Philip Levy, MD, FACE

Victor L. Roberts, MD, MBA, FACP, FACE

Endocr Pract. 2007;13:260-268

Access Roadmap at:

www.aace.com/pub Revision April 2008

© 2008 AACE. All rights reserved. No portion of the Roadmap may be altered,

reproduced or distributed in any form without the express permission of AACE.

http://www.aace.com/pub/







We have got more consensus

for pre-diabetes

All persons with pre-diabetes

should participate in a program of

intensive lifestyle management.

Both metformin and acarbose have

strong evidence for reduction in

development of diabetes from pre-

diabetes, and because of their safety, may be acceptable

therapeutic strategies.

AACE Pre-diabetes Guidelines. July 2008.



Ada ted from: htt : www.diabetes.fi en lish risktest



Interpretations…

Adapted from: http://www.diabetes.fi/english/risktest/



Adapted from: http://www.diabetes.fi/english/risktest/

Score<7 Score7-14

Diabetes Risk Score

Score > 15

Advice/ written info

CVDGestational

DM

OGTT

T2DM Normal IFG IGT

Treatment of hyperglycemiaAnd risk factors INTERVENTION

Follow up



STOP



• The STOP-NIDDM Trial has shown that, in IGT

subjects, the a-glucosidase inhibitor acarbose

can:

• decrease the risk of type 2 diabetes by 36 %;

and,• increase the reversion to normal glucose

tolerance by 42 %.

STOPNIDDM

PREVENTION of T2DMAND CARDIOVASCULAR DISEASE



Glucobay®

IGT: impaired glucose tolerance; ns: not significantYang WY, et al. Chin J Endocrinol Metab 2001;17:131 –6.

Chinese Prevention Study: Glucobay ® reducesthe risk of progression from prediabetes to type 2

diabetes

2.0

4.1

8.2

11.6

0

2

4

6

8

10

12

14

Control Diet and

exercise

Metformin A n n u a l i n c i d e n c e o f d i a b

e t e s ( % )

ns88%

p = 0.000177%

p = 0.0002

3-year decrease in risk of diabetes vs control

Glucobay®



Yang et al:

Status of IGT subjects after 3 years of treatment (%)

NGT IGT DM

Control 27.7 37.4 34.9(n =83)

Diet & Exercise. 28.1 47.4 24.6(n = 60)

Metformin 44.4 43.2 12.4

(n=88)

Acarbose 71.1 22.9 6.0

(n=88)



1) Our results showed that the natural diabetes

incidence was 11.6% in IGT population, and

8.2% in population with conventional diet and

exercise interventions, between which there wereno significant difference.

2) The pharmacological interventions with Acarbose

or Metformin can significantly decrease the IGT

conversion to diabetes.3) The pharmacological interventions reduce DM

risk by about 80%.

CONCLUSIONS

prediabetes_oke_idi lmgn.ppt

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