The association between insulin resistance and endotheliopathy.

Vascular endothelium is involved in the regulation of vascular tone, vessel permeability, and angiogenesis. Vessel tone is determined by the balance of various paracrine vasodilatory and vasoconstrictor factors, most notably nitric oxide (NO) and endothelin-1. Not surprisingly, endothelial dysfunction is believed to be crucial in the development of the chronic vascular complications of diabetes. Endothelial dysfunction, which may be examined by studying endothelial-dependent vasodilatation in humans, is also disturbed by many of the individual features of the insulin resistance syndrome including hypertension, dyslipidaemia, and hyperglycaemia. Therefore, it may be possible that endothelial dysfunction could be closely associated with, or even a common antecedent of, the insulin resistance syndrome (IRS). There is emerging evidence that impaired endothelial-dependent vasodilatation is present in populations at future risk of diabetes and even in children of low birth weight, who may exhibit features of the insulin resistance syndrome in later life. Endothelial dysfunction is an obvious therapeutic target if the vascular pathology associated with insulin resistance and type 2 diabetes is to be ameliorated.