The effects of insulin on the endothelium.

Recent data suggest that diabetes in general, and particularly diabetes in association with insulin resistance, obesity, and hyperglycemia, results in inflammatory changes including the production of cytokines, adhesion molecules, and reactive oxygen species that are toxic to the endothelium and could lead to vascular damage. Insulin suppresses these effects, either indirectly by decreasing glucose levels or directly by stimulating nitric oxide production and inhibiting important pathways in the inflammatory cascade. In addition, insulin directly reduces plasma concentrations of adhesion molecule production in endothelial cells and thus may decrease vascular inflammation. Some of these effects of insulin may be attenuated in patients with insulin resistance, and this finding may provide a mechanistic link for the increase in vascular disease seen in patients with insulin resistance. Doses of insulin adequate to restore normoglycemia may help overcome these abnormalities, although some patients may require insulin sensitization with lifestyle changes or pharmacologic therapy.