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)