Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus.

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.