Lessons learned from landmark trials of type 2 diabetes mellitus and potential applications to clinical practice.

Landmark studies have demonstrated that diabetes is a significant risk factor for cardiovascular disease and mortality. Strong relationships exist between insulin resistance/hyperglycemia and mortality, microvascular complications, and cardiovascular complications. Lipid abnormalities frequently associated with type 2 diabetes and insulin resistance include low high-density lipoprotein cholesterol (HDL-C) and elevated triglyceride levels. Lowering low-density lipoprotein cholesterol levels has been shown to improve the prognosis of patients with diabetes, and increasing HDL-C levels will significantly reduce the incidence of major coronary events. Higher levels of insulin sensitivity are associated with thinner intimal-medial thickness of the carotid artery, which indicates less atherosclerosis. Thiazolidinediones increase insulin sensitivity, decrease intimal-medial thickness, and appear to have inhibitory effects on the progression of atherosclerotic lesions. It is hoped that by preventing the onset of diabetes in high-risk individuals--and improving insulin sensitivity with lifestyle changes or pharmacologic treatment--the profound complications of type 2 diabetes will be prevented or delayed, as well.