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

  1. Antoine Avignon, MD, PHD1,2,6
  1. 1INSERM U1046, Physiologie & Médecine Expérimentale du Cœur et des Muscles, Montpellier, France
  2. 2Université Montpellier I, Université Montpellier II, Montpellier, France
  3. 3INSERM, U1060, Laboratoire CarMeN, INRA 1235, Faculté de Médecine Lyon Sud, Université Lyon 1, Oullins, France
  4. 4Centre de Recherche en Nutrition Humaine Rhône-Alpes and Centre Européen Nutrition Santé, Pierre Bénite, France
  5. 5INRA UMR 866, Unité Dynamique Musculaire et Métabolisme, Montpellier, France
  6. 6Centre Hospitalier Universitaire Montpellier, Montpellier, France
  7. 7Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
  8. 8UMR 204, Nutripass, Université Montpellier I, Montpellier, France
  1. Corresponding author: Antoine Avignon, a-avignon{at}
  1. M.H. and E.B. contributed equally to this work


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 < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid–reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs.

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.

  • Received August 15, 2012.
  • Accepted November 10, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.