Manipulating the vascular biology of coronary atherosclerosis in diabetes: new opportunities.

ore than 7 million people in the United States of America have diabetes mellitus, and type 2 diabetes and the insulin resistance syndrome are increasingly prevalent. This is thought to be the result of the aging of the population, the increasing prevalence of obesity, the growing contribution of highrisk minority groups, and a lower glycemic threshold for the diagnosis of diabetes. The insulin resistance syndrome (syndrome X) describes the clustering of a number of metabolic abnormalities that are risk factors for both diabetes mellitus and atherosclerotic cardiovascular disease.1 These risk factors include hyperinsulinemia, impaired glucose tolerance, hypertension, and a characteristic dyslipidemia (Table I).2 An alternative name, the cardiovascular dysmetabolic syndrome, has been proposed in an effort to emphasize the cardiovascular consequences of this syndrome (Table II).3 Accelerated atherosclerosis is a common and very important feature of both diabetes and insulin resistance, and atherosclerotic cardiovascular disease is responsible for at least three quarters of all diabetesrelated deaths.4,5 Microvascular complications of diabetes are improved by maintenance of tight long-term glycemic control, whereas it has proved difficult to show that atherosclerosis of the large conduit arteries and its complications are prevented by glycemic control.6,7 Aggressive treatment of cardiovascular risk factors associated with the insulin resistance syndrome and diabetes mellitus, including hypertension and dyslipidemia, is effective in reducing the relative risk of cardiovascular events in diabetic patients.8,9 This review focuses on the cell/vessel wall dysfunctions in these syndromes that cause atherosclerosis and the new therapeutic opportunities that follow.