Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus

Abstract

Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients. We investigated whether impaired endothelium-dependent vasodilation (EDV) in diabetes can be improved by long-term administration of oral antioxidants. Forty-nine diabetic subjects [26 Type 1 (T1) and 23 Type 2 (T2)] and 45 matched healthy control subjects were randomized to receive oral vitamin C (1,000 mg) and vitamin E (800 IU) daily or matching placebo for 6 mo. Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation (EIV). EDV was decreased in both T1 (4.9 +/- 0.9%, P = 0.015) and T2 (4.1 +/- 1.0%, P < 0.01) subjects compared with control subjects (7.7 +/- 0.7%). EIV was decreased in T2 (15.0 +/- 1.2%, P < 0.01) but not T1 subjects (18.5 +/- 2.3%, P = 0.3) compared with controls (21.8 +/- 1.8%). Administration of antioxidant vitamins increased EDV in T1 (by 3.4 +/- 1.4%, P = 0.023) but not T2 subjects (by 0.5. +/- 0.4%, P = 0.3). Antioxidant therapy had no significant affect on EIV. Oral antioxidant therapy improves EDV in T1 but not T2 diabetes. These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients.

Endothelial Function Varies According to Insulin Resistance Disease Type

“…The response to nitroglycerin was attenuated in subjects with type 2 diabetes and lipodystrophic diabetes. We have previously reported an impaired response to nitroglycerin in subjects with type 2 diabetes (44), but this is the first report of a similar finding in subjects with lipodystrophic diabetes. Markers of insulin resistance, adipokines, and inflammation did not associate with vascular smooth muscle function.…”

“…Glucose levels correlated inversely with smooth muscle function. The attenuation in endothelium-independent vasodilation may relate to chronic hyperglycemia as reflected in attenuation of nitroglycerin-mediated vasodilation in diabetes (44,45). Despite the attenuation in endothelium-independent vasodilation in the subjects with lipodystrophic diabetes, flow-mediated, endotheliumdependent vasodilation was preserved.…”

Antioxidants, Diabetes, and Endothelial Dysfunction

“…In a recent study, combined therapy with vitamins C and E in types I and II diabetic patients showed an improvement in endothelial function only in type I diabetic patients. 54 In another study, high oral doses of vitamin C did not improve endothelial function in type II diabetic subjects. 55 Interestingly, in this study, although the diabetic patients with low vitamin C levels were able to replenish their vitamin C levels with the high-dose oral supplementation, they did not achieve as high levels as healthy non-diabetic subjects.…”

Reactive oxygen species, reactive nitrogen species and antioxidants in etiopathogenesis of diabetes mellitus type-2

“…Again it may be pointed out that this association was not significant. Beckman et al (128) reported that administration of vitamin E and C in the doses of 800 IU/d and 1000 mg/d respectively for six months alleviated vasorelaxation in DMT-1 but not in DMT-2. Another A combination of vitamins E and C in the doses of 680 mg/d and 1250 mg/d improved renal function in DMT-2 patients.…”