High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance

Abstract

Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 ± 2 μM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 μM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group ( n = 17 subjects), plasma vitamin C (22 ± 3 μM), fasting glucose (159 ± 12 mg/dl), insulin (19 ± 7 μU/ml), and SIClamp [2.06 ± 0.29 × 10−4 dl·kg−1·min−1/(μU/ml)] did not change significantly after placebo treatment. In the vitamin C group ( n = 15 subjects), basal plasma vitamin C (23 ± 2 μM) increased to 48 ± 6 μM ( P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 μM). No significant changes in fasting glucose (156 ± 11 mg/dl), insulin (14 ± 2 μU/ml), SIClamp [2.71 ± 0.46 × 10−4 dl·kg−1·min−1/(μU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes.