Determinants of coronary vascular disease in patients with type II diabetes mellitus and their therapeutic implications.

Cardiovascular morbidity and mortality are increased 4- to 6-fold in patients with type II diabetes. The high prevalence is multifactorial and reflects in part the adverse influence of covariate, cardiac risk factors such as hypertension and hyperlipidemia. Type II diabetes is characterized by insulin resistance, hyperinsulinemia, and altered carbohydrate and lipid metabolism resulting in hyperglycemia, increased concentrations in blood of very low-density and low-density lipoproteins, and decreased blood high-density lipoproteins. Abnormalities seen predispose to vasculopathy through lipid deposition into vessel walls associated with monocyte infiltration, vascular smooth muscle cell proliferation, arterial mural fibrosis, and thrombosis. Conventional therapy for cardiovascular disease such as angioplasty and bypass surgery are of only limited efficacy. Thus, retardation of progression of atherosclerosis is essential. In addition to focusing on co-existent cardiac risk factors such as hypertension, therapy for patients with type II diabetes should reduce or reverse insulin resistance, improve metabolic control, and, ideally, do so without exacerbating hyperinsulinemia. Diet and exercise are central, and novel orally active hyperglycemic agents such as the biguanides and the thiazolidinediones that sensitize diverse tissues to insulin offer particular promise.