The association of the insulin resistance syndrome with elevated triglyceride levels and low high-density lipoprotein (HDL) levels has been consistent in both sexes and all major ethnic groups. More recently, changes in other lipoprotein fractions (known to be atherogenic), including a preponderance of small, dense low-density lipoprotein (LDL) and excess triglyceride-rich remnants, have also been associated with insulin resistance. Data show this dyslipidemia to be caused by characteristics of the insulin-resistant state itself rather than by elevated insulin concentrations or obesity.
Howard looked closely at the three components of dyslipidemia in insulin resistance and the potential effects of interventions. Altered metabolism leads to very low-density lipoprotein (VLDL) overproduction as well as decreased lipoprotein lipase levels, causing decreased clearance of VLDL. This condition results in more triglyceride-risk particles, fewer HDL particles and more small, dense LDL particles. Several mechanisms appear to decrease the smaller HDL particles, causing increased atherogenesis. The preponderance of small, dense LDL contributes to increased apo B, which increases assembly and secretion of VLDL.
The goal of treating dyslipidemias in insulin resistance is prevention of cardiovascular disease. The dyslipidemia characteristic of insulin resistance includes normal or only moderately elevated LDL levels, elevated VLDL and low HDL levels. Many of these patients are obese. Lipid lowering using the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin caused a 27 percent reduction in coronary events in diabetic patients compared with a 22 percent reduction in nondiabetic patients. The treatment caused a reduction in LDL and triglyceride levels, as well as an increase in HDL levels.
Weight loss in insulin-resistant persons can significantly improve insulin action, decrease triglyceride levels, increase HDL levels and normalize LDL particle size. Exercise has the same effect. Metformin decreases LDL and triglyceride levels by improving glycemic control or by causing weight loss. Troglitazone appears to decrease triglyceride levels in a dose-related manner, with an accompanying increase in HDL levels.
The author concludes that the dyslipidemia associated with insulin resistance has a major role in atherosclerosis. The best approach in the insulin-resistant patient has not yet been determined, but efforts to decrease insulin resistance may decrease cardiovascular risk.