title: Grape polyphenols prevent fructose-induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients.
abstract: 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.
  
  
  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.
authors.affiliation: INSERM U1046, Physiologie & Médecine Expérimentale du Cœur et des Muscles, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Hokayem
authors.forename: Emilie
authors.initials: E
authors.lastname: Blond
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Karen
authors.initials: K
authors.lastname: Lambert
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Meugnier
authors.forename: Christine
authors.initials: C
authors.lastname: Feillet-Coudray
authors.forename: Charles
authors.initials: C
authors.lastname: Coudray
authors.forename: Sandra
authors.initials: S
authors.lastname: Pesenti
authors.forename: Cedric
authors.initials: C
authors.lastname: Luyton
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lambert-Porcheron
authors.forename: Valerie
authors.initials: V
authors.lastname: Sauvinet
authors.forename: Christine
authors.initials: C
authors.lastname: Fedou
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Brun
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.forename: Catherine
authors.initials: C
authors.lastname: Bisbal
authors.forename: Ariane
authors.initials: A
authors.lastname: Sultan
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.forename: Joelle
authors.initials: J
authors.lastname: Goudable
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Cristol
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Antoine
authors.initials: A
authors.lastname: Avignon
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000009:adverse effects*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D059808:Polyphenols / Q000737:chemistry / Q000627:therapeutic use*; D027843:Vitis / Q000737:chemistry*
chemical_list: D059808:Polyphenols; D005632:Fructose