Diabetic Dyslipidemia and Atherosclerosis

Posted by e-Medical PPT Saturday, September 1, 2012
Interrelation Between Atherosclerosis and Insulin Resistance
Insulin resistance is associated with a panoply of abnormalities, including hypertension, hyperinsulinemia, hypertriglyceridemia with small, dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL), and hypercoagulability.  Of course, insulin resistance is a major risk factor for the development of diabetes.  Obesity plays a role both in exacerbating insulin resistance and as an independent risk factor for atherosclerosis.  Therefore, any patient with insulin resistance has numerous reasons to be at very high risk for atherosclerosis.

Insulin Resistance and Hyperinsulinemia: Clinical Clues
Clues for the identification of hyperinsulinemic or insulin-resistant patients include abdominal obesity and the presence of hypertriglyceridemia and low HDL cholesterol.  Glucose intolerance can sometimes be identified by the fasting glucose level, which may be between 100 and 125 mg/dL.  Other characteristics of insulin-resistant individuals are hypertension and the presence of atherosclerotic cardiovascular disease.  Also, certain ethnic groups, such as those from Southeast Asia and Native Americans, have very high genetic predispositions to develop insulin resistance.

Dyslipidemia in the Insulin Resistance Syndrome
Dyslipidemia in patients with the insulin resistance syndrome is characterized by an elevated level of total triglyceride, a reduced level of HDL cholesterol, and the presence of heterogeneity within LDL particles, with an increased proportion of LDL found as small, dense, cholesterol-poor particles.

Small, Dense LDL and CHD: Potential Atherogenic Mechanisms
Data from in vitro and in vivo studies suggest that small, dense LDL may be particularly atherogenic.  In vitro, small, dense LDL appears to be more susceptible to oxidative modification.  Because they are smaller, these particles appear to penetrate the endothelial layer of the arterial wall more easily.  The apo B molecule in small, dense LDL undergoes a conformational change that leads to decreased affinity for the LDL receptor, therefore allowing this LDL particle to remain in the circulation longer and be more liable to oxidative modification and uptake into the vessel wall.  Finally, in population studies and small clinical studies, small, dense LDL is associated with the insulin-resistance syndrome as well as with high triglycerides and low HDL cholesterol.

Factors Promoting Thromboembolic Disease in Diabetes
Diabetes is associated with hypercoagulability and the predisposition for thromboembolic phenomena.  Diabetics have increased fibrinogen, increased PAI-1 levels, and increased platelet aggregability; the latter is particularly a problem in the poorly controlled diabetic.

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