Clinical Studies
Vitamin C Improves Endothelium-Dependent Vasodilation in Patients With Insulin-Dependent Diabetes Mellitus,☆☆

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Abstract

Objectives. We sought to determine whether the antioxidant vitamin C improves endothelium-dependent vasodilation of forearm resistance vessels in patients with insulin-dependent diabetes mellitus.

Background. Endothelium-dependent vasodilation is impaired in patients with diabetes mellitus. Oxidatively mediated degradation of endothelium-derived nitric oxide contributes to abnormal endothelium-dependent vasodilation in animal models of diabetes mellitus.

Methods. The study group included 10 patients with insulin-dependent diabetes mellitus and 10 age-matched control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3 to 10 μg/min). Endothelium-independent vasodilation was assessed by intraarterial infusion of nitroprusside (0.3 to 10 μg/min). Forearm blood flow dose–response curves were determined for each drug infusion before and during concomitant infusion of vitamin C (24 mg/min).

Results. In diabetic subjects, endothelium-dependent vasodilation was augmented by the concomitant infusion of vitamin C (p = 0.001). Endothelium-independent vasodilation was not affected by the concomitant infusion of vitamin C (p = NS). In control subjects, vitamin C infusion did not affect endothelium-dependent vasodilation (p = NS).

Conclusions. Vitamin C selectively restores the impaired endothelium-dependent vasodilation in the forearm resistance vessels of patients with insulin-dependent diabetes mellitus. These findings indicate that nitric oxide degradation by oxygen-derived free radicals contributes to abnormal vascular reactivity in humans with insulin-dependent diabetes mellitus.

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This research was supported by Program Project Grant HL-48743 in Vascular Biology and Medicine, and Dr. Creager is the recipient of Academic Award HL-02663 in Systemic and Pulmonary Vascular Medicine, from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

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