Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients

OBJECTIVE To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS In the PCB group, fructose induced 1 ) a 20% decrease in hepatic insulin sensitivity index ( P P 2 ) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid–reactive substances and protein carbonylation) oxidative stress ( P 3 ) a downregulation of mitochondrial genes and decreased mitochondrial respiration ( P CONCLUSIONS A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.