Management of diabetes mellitus and insulin resistance in patients with cardiovascular disease.

Patients with diabetes have a greatly increased relative risk of developing cardiovascular disease when compared with patients without diabetes. Much of this risk is related to insulin resistance and is associated with both traditional and nontraditional cardiovascular risk factors. Therapy for diabetes must address these risk factors in an attempt to prevent and adequately treat cardiovascular disease. Pharmacologic therapy directed toward dyslipidemia and hypertension has a beneficial effect on risk factors and has been shown to decrease cardiovascular events. The effects of insulin and oral hypoglycemic agents on insulin resistance are variable, and their direct effect on cardiovascular disease is less clear. Metformin is the only oral hypoglycemic agent shown to decrease cardiovascular events independent of glycemia. The thiazolidinediones directly improve insulin resistance, decrease plasma insulin concentration, and have the potential to decrease the risk of cardiovascular disease in patients with diabetes. A number of studies have demonstrated that the thiazolidinediones produce changes in several cardiovascular risk factors associated with the insulin resistance syndrome, including lowering blood pressure, correcting diabetic dyslipidemia, improving fibrinolysis, and decreasing carotid artery intima-medial thickness. These agents bind a newly described class of receptors, peroxisome proliferator-activated receptors, which may have implications for atherosclerosis. Although these drugs increase low-density lipoprotein (LDL) cholesterol, they induce a favorable change in the LDL particle size and susceptibility to oxidation. Long-term clinical trials are being conducted to determine the effect that thiazolidinediones have on cardiovascular events in individuals with type 2 diabetes.