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1 Diabetes Unit, NIH, NCCAM, Bethesda, MD, USA
2 Cardiology Branch, NIH, NHLBI, Bethesda, MD, USA
3 Digestive Disease Branch, NIH, NIDDK, Bethesda, MD, USA
* To whom correspondence should be addressed. E-mail: quonm{at}nih.gov.
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). Thirty two diabetic subjects with plasma vitamin C < 40 µM were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C, 800 mg/day for 4 weeks. Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to acetylcholine (ACh), sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 weeks of treatment. In the placebo group (n = 17), plasma vitamin C (22 ± 3 µM), fasting glucose (159 ± 12 mg/dl), insulin (19 ± 7 µU/ml), and SIClamp (2.06 ± 0.29) did not change significantly after placebo treatment. In the vitamin C group (n = 15), 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), 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.
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