Endothelial dysfunction, inflammation, and insulin resistance: a focus on subjects at risk for type 2 diabetes.

Subjects with obesity, family history of type 2 diabetes, polycystic ovary syndrome, previous gestational diabetes, dyslipidemia, hypertension, impaired glucose tolerance or impaired fasting glucose, and those with metabolic syndrome are at risk for the development of type 2 diabetes. Some of them are also at risk for cardiovascular disease. Some underlying abnormalities such as insulin resistance, endothelial dysfunction, and low-grade chronic inflammation are frequently present and closely associated in all these groups. The flow of substrates, hormones, and cytokines from visceral fat to skeletal muscle and to the endothelial cells, along with some genetic abnormalities that lead to impaired insulin action in the peripheral tissues and to impaired insulin-stimulated nitric oxide production in endothelial cells, may play a role in establishing these shared metabolic and vascular derangements. Weight loss, thiazolidinediones, and metformin improve vascular function in subjects at risk for type 2 diabetes and may prove to reduce cardiovascular events in these individuals.