Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients
- Marie Hokayem, MS1,2,
- Emilie Blond, PHARMD3,4,
- Hubert Vidal, PHD3,4,
- Karen Lambert, PHD1,2,
- Emmanuelle Meugnier, PHD3,
- Christine Feillet-Coudray, PHD5,
- Charles Coudray, PHD5,
- Sandra Pesenti, BS3,
- Cedric Luyton, MD, PHD4,
- Stéphanie Lambert-Porcheron, MD, PHD4,
- Valerie Sauvinet, MS3,4,
- Christine Fedou, MD, PHD1,2,6,
- Jean-Frédéric Brun, MD, PHD1,2,6,
- Jennifer Rieusset, PHD3,4,
- Catherine Bisbal, PHD1,2,
- Ariane Sultan, MD, PHD1,2,6,
- Jacques Mercier, MD, PHD1,2,6,
- Joelle Goudable, PHD3,4,
- Anne-Marie Dupuy, MD, PHD7,
- Jean-Paul Cristol, MD, PHD7,8,
- Martine Laville, MD, PHD3,4 and
- Antoine Avignon, MD, PHD1,2,6⇓
- 1INSERM U1046, Physiologie & Médecine Expérimentale du Cœur et des Muscles, Montpellier, France
- 2Université Montpellier I, Université Montpellier II, Montpellier, France
- 3INSERM, U1060, Laboratoire CarMeN, INRA 1235, Faculté de Médecine Lyon Sud, Université Lyon 1, Oullins, France
- 4Centre de Recherche en Nutrition Humaine Rhône-Alpes and Centre Européen Nutrition Santé, Pierre Bénite, France
- 5INRA UMR 866, Unité Dynamique Musculaire et Métabolisme, Montpellier, France
- 6Centre Hospitalier Universitaire Montpellier, Montpellier, France
- 7Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
- 8UMR 204, Nutripass, Université Montpellier I, Montpellier, France
- Corresponding author: Antoine Avignon, .
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.
- © 2012 by the American Diabetes Association.
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