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Insulin Causes Endothelial Dysfunction in Humans *

Background Insulin resistance is often accompanied by hyperinsulinemia and may predispose to atherosclerosis. Endothelium plays a central role in atherogenesis. The in vivo effects of hyperinsulinemia on endothelial function of large conduit arteries are unknown.

Methods and Results Twenty-five healthy subjects were enrolled for study. In study A (n=9), subjects underwent both a time-control saline study and a euglycemic low-dose insulin (insulin {approx}110 pmol/L) clamp for 6 hours. Study B (n=5) was identical to study A except that the euglycemic clamp was performed at high physiological insulin concentrations ({approx}440 pmol/L). In study C (n=7), subjects underwent two 4-hour euglycemic insulin ({approx}110 pmol/L) clamps with and without the concomitant infusion of an antioxidant (vitamin C).

 In study D (n=4), two saline time-control studies were performed with and without the concomitant infusion of vitamin C. In all studies, both at baseline and throughout the experimental period, endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-induced) vasodilation was assessed in femoral and brachial arteries by echo Doppler.

Both low (study A) and high physiological (study B) hyperinsulinemia abolished endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was unaffected. Vitamin C fully restored insulin-impaired endothelial function without affecting endothelium-independent vasodilation (study C). Vitamin C had no effects on endothelium-dependent or endothelium-independent vasodilation during saline control studies (study D).

Conclusions Modest hyperinsulinemia, mimicking fasting hyperinsulinemia of insulin-resistant states, abrogates endothelium-dependent vasodilation in large conduit arteries, probably by increasing oxidant stress. These data may provide a novel pathophysiological basis to the epidemiological link between hyperinsulinemia/insulin-resistance and atherosclerosis in humans.

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As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

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Published on 10-15-2007