Resistensi Insulin :

Apa & Mengapa Perlu Ditangani pada DM tipe 2

Negara 1995 (juta) Negara 2025 (juta)

Urutan 1 India 19.4 India 57.22 China 16.0 China 37.63 U.S. 13.9 U.S. 21.94 Russian Fed. 8.9 Pakistan 14.55 Japan 6.3 Indonesia 12.46 Brazil 4.9 Russian Fed. 12.27 Indonesia 4.5 Mexico 11.78 Pakistan 4.3 Brazil 11.69 Mexico 3.8 Egypt 8.810 Ukraine 3.6 Japan 8.5

Negara Lainnya 49.7 103.6

Total 135.3 300.0

Sepuluh Negara dengan Perkiraan Jumlah Pasien DM Dewasa Terbanyak, 1995 and 2025

Type 2 Diabetes Is NOT a Mild Disease

DiabeticRetinopathyLeading causeof blindnessin working ageadults1

DiabeticNephropathyLeading cause of end-stage renal disease2

CardiovascularDisease

Stroke2 to 4 fold increase in cardiovascular mortality and stroke3

DiabeticNeuropathyLeading cause of non-traumatic lower extremity amputations5

8/10 diabetic patients die from CV events4

1 Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 3 Kannel WB, et al. Am Heart J 1990; 120:672–676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.

5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79.

Microvascular complication Macrovascular complication

Prediabetes Type 2 diabetes

When Macrovascular & Microvascular Complication in T2DM?

Diabetes duration (years)

Plasmaglucose(mg/dl)

–20 –10 0 10 20 30

126

100

Postprandial

Fasting

Insulin resistance

Insulin level

Adapted from Bergenstal RM, et al. Diabetes mellitus, carbohydrate metabolism and lipid disorders. In Endocrinology. 4th ed. 2001.

Microvascular complications

Macrovascular complications

Relativefunction

Obesity IGT Diabetes (Uncontrolled)

Underlying factors in type 2 DM : IR and -cell dysfunction

Type 2 diabetes

Adapted from DeFronzo RA. Diabetes 1988; 37: 667–87.

hepatic gluc production

glucose uptake

Genetic susceptibilityobesity, sedentary lifestyle

-cell dysfunction insulin secretion

Insulin Resistance

Modified: Ann Intern Med 1999;131:281

Glucose

GLUCOSE PRODUCTION

LIVER

INTESTINE

GLUCOSE ABSORPTION

MUSCLE

GLUCOSE UPTAKE

ADIPOSE TISSUE

PANCREAS

INSULIN SECRETION

1. Defek sekresi insulin

2. Resistensi insulin

Patofisiologi DM tipe 2

Perkembangan Diabetes Tipe 2

Resistensi Insulin

Resistensi Insulin & Hiperinsulinemia dg

Toleransi Glucosa Normal

Resistensi Insulin & Kadar Insulin Menurun dg

Toleransi Glucosa Terganggu (IGT)

Diabetes Tipe 2

Fungsi Sel-Beta

Adapted from Diabetes 1996;45:1661

Natural History of Type 2 Diabetes

Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.

Obesity IFG* Diabetes Uncontrolled Hyperglycemia

50100150200250300350

50

100

150

200

250

Glu

cose

(mg/

dL)

Rel

ativ

eFu

nctio

n (%

)

Post-meal Glucose

Fasting Glucose

Insulin Resistance

Insulin Level-cell Failure

*IFG = impaired fasting glucose

Years of Diabetes-10 0-5 5 10 15 302520

020

40

60

-1 0 1 2 3 4 5 6

Time from randomization (years)

-C

ell f

unct

ion

(%, H

OM

A a

naly

sis)

The UKPDS demonstrated that loss of glycemic control correlates with progressive loss of -cell function

UK Prospective Diabetes Study Group. Diabetes 1995; 44:1249–1258.

1. Defek sekresi insulin

2. Resistensi insulin

Patofisiologi DM tipe 2

Definisi RESISTENSI INSULIN

Gangguan respon terhadap efek fisiologis insulin,

(Diabetes Care 2000; 23(Suppl 1):54

• glukosa• lipid• protein• fungsi endotel.

meliputi gangguan metabolisme:

Normal glucose metabolism

Impaired glucose metabolism

Type 2 diabetes

Insulin sensitivity Insulin secretion

30%

70%

100%

50%

150%

100%

Diabetes Obes Metab 1999; 1(1): S1

IGT50% 70-100%

Natural History of Type 2 Diabetes

AtherosclerosisType 2 diabetes

Impairedglucose tolerance

Polycysticovary disease

Obesity (central)

Dyslipidemia Hypertension

Acanthosisnigricans

Hyperuricemia

Decreasedfibrinolytic activity

InsulinResistance

KLINIS

Insulin Resistance: Associated Conditions

Insulin resistance and -cell dysfunction are linked and are underlying factors in type 2 diabetes

Insulinresistance

High insulin demand

glucotoxic

ity

lipotoxicity

Increased lipolysis and release of free fatty acids

Elevated circulating FFA

Decreased glucose uptake into muscle and adipose tissue and raised hepatic glucose output

Hyperglycemia

Type 2 diabetes

-Cell dysfunction

Increased lipolysis

Decreased glucose uptake into muscle and adipose tissue and raised hepatic

glucose output

Hyperglycemia

Insulin resistance

-cell dysfunction

High insulin demand and insulin resistance in

pancreas

Elevated circulating FFA

glucotoxicitylipotoxicity

Elevated circulating FFA is a central factor in the development of type 2 diabetes

Arner P. Diabetes Obes Met 2001;3 (Suppl.1); S11–S19.

Management DM tipe 21. Non-Farmakologis:

Pola makan & OR

2. Farmakologis :

Obat (OAD)

ref version 2.1

Major Metabolic Defects in Type 2 Diabetes

• Peripheral insulin resistance in muscle and fat

• Impaired pancreatic insulin secretion

• Increased hepatic glucose output

Diabetes Care, 1999; 22:562

Sites of Action of Current OAD

GLUCOSE PRODUCTION

MUSCLE

PERIPHERAL GLUCOSE UPTAKE & UTILIZATION

INSULIN SECRETION

ADIPOSE TISSUE

LIVER

Modified: Ann Intern Med 1999;131:281

INTESTINE

GLUCOSE ABSORPTION

-glucosidase inhibitors

PANCREAS

Biguanides

Biguanides

Glucose

SulphonylureasMeglitinides

Thiazolidinediones

Thiazolidinediones

Terima Kasih

Atas Perhatiannya

TesGD Sewaktu

GD puasa

Batasan kadar glukosa darah

100 - 199

140 - 199

> 200

> 126

TGT / IGT = Toleransi Glukosa Terganggu / Impaired Glucose Tolerance

Belum Pasti DM

TTGO = Tes Toleransi Glukosa Oral (Puasa 8 jam, minum 75g glukosa 2 jam di test

100 – 125*

< 140

DM

(mg/dL, darah Vena)

< 100

< 100

> 200

TGT / IGT DMTG normal

TTGO

Bukan DM

* Glukosa darah puasa terganggu

(Konsensus PERKENI 2006)