00000110_糖尿病与动脉粥样硬化

糖尿病与动脉粥样硬化

Diabetic Dyslipidemia and Atherosclerosis Henry Ginsberg, MD

糖尿病与动脉粥样硬化

Interrelation Between Atherosclerosis and Insulin ResistanceHypertension Obesity Hyperinsulinemia

Insulin Resistance

Diabetes Hypertriglyceridemia Small, dense LDL Low HDL Hypercoagulability

Atherosclerosis

糖尿病与动脉粥样硬化

Insulin Resistance and Hyperinsulinemia: Clinical CluesAbdominal obesity TG + HDL-C

Glucose intolerance Hypertension Atherosclerosis Ethnicity

糖尿病与动脉粥样硬化

Dyslipidemia in the Insulin Resistance SyndromeElevated total TG Reduced HDL-C Small, dense LDL-C

糖尿病与动脉粥样硬化

Dyslipidemias in Adults with Diabetes Framingham Heart StudyMENNormal Increased cholesterol Increased LDL Decreased HDL Increased triglycerides 14% 11% 12% 9% DM 13% 9% 21% 19%

WOMENNormal 21% 16% 10% 8% DM 24% 15% 25% 17%

Garg A et al. Diabetes Care 1990;13:153-169.

糖尿病与动脉粥样硬化

Mean Plasma Lipids at Diagnosis of Type 2 Diabetes - UKPDSMENType 2 Number of Pts TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) 2139 213 139 39** 159* Control 52 205 132 43 103

WOMENType 2 1574 224 151* 43* 159* Control 143 217 135 55 95

* P<0.001, ** P<0.02 comparing type 2 vs. controll UKPDS Group. Diabetes Care 1997;20:1683-1687.

糖尿病与动脉粥样硬化

Relation Between Insulin Resistance and Hypertriglyceridemia625 Plasma TG (mg/dL) 500 400 300 200 100 100 200 300 400 500 600 Insulin Response to Oral Glucose** Total area under 3-hour response curve (mean of 2 tests). Olefsky JM et al. Am J Med. 1974;57:551-560.

r = 0.73 P < 0.0001

糖尿病与动脉粥样硬化

Association Between Hyperinsulinemia and Low HDL-C HDL60P<0.005 HDL-C (mg/dL) C Hyperinsulinemic Normoinsulinemic P<0.005

50 40 30 20Nonobese

Obese

Reaven GM. In: LeRoith D et al., eds. Diabetes Mellitus. Philadelphia: Lippincott-Raven,1996:509-519.

糖尿病与动脉粥样硬化

Mechanisms Relating Insulin Resistance and DyslipidemiaFat Cells FFA Liver

IR X

Insulin

糖尿病与动脉粥样硬化

Mechanisms Relating Insulin Resistance and DyslipidemiaFat Cells FFA TG Apo B VLDL VLDL Liver

IR X

Insulin

糖尿病与动脉粥样硬化

Mechanisms Relating Insulin Resistance and DyslipidemiaFat Cells FFA TG Apo B VLDL Liver CEVLDL (CETP) HDL

(hepatic lipase) Apo A-1 AKidney

IR X

TG

Insulin

糖尿病与动脉粥样硬化

Mechanisms Relating Insulin Resistance and DyslipidemiaFat Cells FFA TG Apo B VLDL Liver CEVLDL (CETP) HDL

(hepatic lipase) Apo A-1 AKidney

IR X

TG

CE (CETP) TG Insulin LDL SD LDL

(lipoprotein or hepatic lipase)

糖尿病与动脉粥样硬化

Dyslipidemia in DiabetesIncreased Decreased

Triglycerides VLDL LDL and small dense LDL Apo B

HDL Apo A-I

糖尿病与动脉粥样硬化

LDL Subclass Phenotypes in Diabetes MellitusLDL Subclass n Men* Diabetic Nondiabetic Women** Diabetic Nondiabetic 29 87 54 543 A 28 47 34 85 Int Percent 21 29 30 9 B 51 24 36 6

* Feingold KR et al. Arterioscler Thromb 1992; 12:1496-1502. ** Selby JV et al. Circulation 1993; 88:381-387.

糖尿病与动脉粥样硬化

Small Dense LDL and CHD: Potential Atherogenic MechanismsIncreased susceptibility to oxidation Increased vascular permeability Conformational change in apo B Decreased affinity for LDL receptor Association with insulin resistance syndrome Association with high TG and low HDLAustin MA et al. Curr Opin Lipidol 1996;7

:167-171.

糖尿病与动脉粥样硬化

Hypertriglyceridemia and CHD Risk: Associated AbnormalitiesAccumulation of chylomicron remnants Accumulation of VLDL remnants Generation of small, dense LDL-C Association with low HDL-C Increased coagulability plasminogen activator inhibitor (PAI-1) factor VIIc

- Activation of prothrombin to thrombin