Abstract 164: the Effects of Resveratrol Treatment on Vascular Function in Type 2 Diabetes Mellitus

Patients with diabetes mellitus (DM) have abnormal vascular function characterized by premature aging and aortic stiffness. In animal models of metabolic disease, the plant-derived polyphenol, resveratrol, decreases arterial stiffness through SirT1 activation. Therefore, we hypothesized that resveratrol would improve vascular function and activate SirT1 in patients with DM. We performed a randomized, double-blind, placebo-controlled crossover study of resveratrol supplementation in 57 patients with DM (age 56±8 years, female 52%, African-American 67%, BMI 31.7±4.4 kg/m 2 ). Patients consumed resveratrol 100 mg/d for 2 weeks followed by 300 mg/d for 2 weeks or a matched placebo containing no polyphenols with a two-week wash-out period between treatments. In the overall study group, there was a trend toward lower carotid-femoral pulse wave velocity (CFPWV) with resveratrol treatment (P=0.18). In a subset of patients with high arterial stiffness at baseline, resveratrol treatment lowered CFPWV without a change in systemic blood pressure consistent with reduced central aortic stiffness (Figure). Brachial artery flow-mediated dilation, reactive hyperemia, and pulse amplitude tonometry did not change. In a subset of 7 patients, we collected venous endothelial cells by J-wire biopsy and observed a trend toward increased SirT1 activity with resveratrol treatment. Our findings suggest that resveratrol supplementation may reverse arterial stiffening in patients with DM potentially through activation of endothelial SirT1 activity.