Oral Vitamin C Impact on Insulin Sensitivity and Vascular Reactivity in Type 2 Diabetes

Diabetes is characterized by decreased sensitivity to the actions of insulin to promote both glucose utilization and vasodilation in skeletal muscle beds. Insulin's vasodilator action is mediated, in part, by endothelial-derived nitric oxide (NO). Increased blood flow accounts for approximately 25% of the increase in skeletal muscle glucose disposal mediated by insulin. Therefore, endothelial dysfunction may contribute to insulin resistance. Intraarterial administration of vitamin C improves NO-dependent vascular reactivity in diabetic subjects (but not normal subjects). This may be due to antioxidant properties of vitamin C that result in relative increases in the level of NO in the diabetic vasculature. In this exploratory protocol, our primary objective is to assess the effects of oral administration of vitamin C on both insulin sensitivity and endothelial function in subjects with type 2 diabetes. A secondary, peripheral objective, is to study these effects in vitamin C-deficient clinical research volunteers. Hyperinsulinemic euglycemic glucose clamp procedures and forearm blood flow measurements will be used to assess both insulin sensitivity and vascular reactivity in diabetic subjects and clinical research volunteers who have plasma vitamin C levels less than 30 microM. The subjects will then be given either placebo or oral vitamin C supplementation (800 mg/day) for four weeks and assessment of insulin sensitivity and vascular reactivity will be repeated. Plasma levels of vitamin C will be measured to confirm that subjects in the experimental group have an appropriate increase in vitamin C levels. We hypothesize that chronic oral administration of vitamin C to diabetic or clinical research volunteers who are deficient in vitamin C will improve insulin sensitivity and endothelial function. Our study will provide information about vitamin C levels in diabetic subjects and may suggest a potential therapy to significantly improve endothelial dysfunction and insulin resistance.