BACKGROUND: Glucose-dependent insulinotropic polypeptide [also known as gastric inhibitory polypeptide (GIP)] and its receptor (GIPR) may link overnutrition to obesity, insulin resistance, and type 2 diabetes. A GIPR variant rs2287019 was recently associated with obesity and glucose metabolism. OBJECTIVE: We aimed to examine whether weight-loss diets that vary in fat content may modify the effect of this variant on changes in body weight, fasting glucose, and insulin resistance in the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. DESIGN: We genotyped the GIPR rs2287019 in 737 overweight adults who were randomly assigned to 1 of 4 weight-loss diets that varied in macronutrient contents for 2 y. We assessed the percentage changes in body weight, fasting glucose, and insulin resistance (HOMA-IR) across genotypes by the low-fat and high-fat diets. RESULTS: At 6 mo of diet intervention, the T allele of rs2287019 was associated with greater weight loss (β ± SE: -1.05 ± 0.56%; P = 0.06) and greater decreases in fasting glucose (β ± SE: -2.33 ± 0.86%; P = 0.006), fasting insulin (β ± SE: -8.76 ± 4.13%; P = 0.03), and HOMA-IR (β ± SE: -10.52 ± 4.39%; P = 0.01) in participants who were assigned to low-fat diets, whereas there was no significant genotype effect on changes in these traits in the group assigned to the high-fat diet (all P > 0.44; P-interaction = 0.08, 0.04, 0.10, and 0.07, respectively). After correction for multiple tests (significant P = 0.008), the genotype effect on changes in fasting glucose remained significant. Sensitivity analysis in white participants showed that the interactions were more evident on changes in insulin and HOMA-IR (P-interaction < 0.008). CONCLUSION: The T allele of GIPR rs2287019 is associated with greater improvement of glucose homeostasis in individuals who choose a low-fat, high-carbohydrate, and high-fiber diet. The POUNDS LOST trial was registered at clinicaltrials.gov as NCT00072995.
RCT Entities:
BACKGROUND:Glucose-dependent insulinotropic polypeptide [also known as gastric inhibitory polypeptide (GIP)] and its receptor (GIPR) may link overnutrition to obesity, insulin resistance, and type 2 diabetes. A GIPR variant rs2287019 was recently associated with obesity and glucose metabolism. OBJECTIVE: We aimed to examine whether weight-loss diets that vary in fat content may modify the effect of this variant on changes in body weight, fasting glucose, and insulin resistance in the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. DESIGN: We genotyped the GIPRrs2287019 in 737 overweight adults who were randomly assigned to 1 of 4 weight-loss diets that varied in macronutrient contents for 2 y. We assessed the percentage changes in body weight, fasting glucose, and insulin resistance (HOMA-IR) across genotypes by the low-fat and high-fat diets. RESULTS: At 6 mo of diet intervention, the T allele of rs2287019 was associated with greater weight loss (β ± SE: -1.05 ± 0.56%; P = 0.06) and greater decreases in fasting glucose (β ± SE: -2.33 ± 0.86%; P = 0.006), fasting insulin (β ± SE: -8.76 ± 4.13%; P = 0.03), and HOMA-IR (β ± SE: -10.52 ± 4.39%; P = 0.01) in participants who were assigned to low-fat diets, whereas there was no significant genotype effect on changes in these traits in the group assigned to the high-fat diet (all P > 0.44; P-interaction = 0.08, 0.04, 0.10, and 0.07, respectively). After correction for multiple tests (significant P = 0.008), the genotype effect on changes in fasting glucose remained significant. Sensitivity analysis in white participants showed that the interactions were more evident on changes in insulin and HOMA-IR (P-interaction < 0.008). CONCLUSION: The T allele of GIPRrs2287019 is associated with greater improvement of glucose homeostasis in individuals who choose a low-fat, high-carbohydrate, and high-fiber diet. The POUNDS LOST trial was registered at clinicaltrials.gov as NCT00072995.
Authors: Gary D Foster; Holly R Wyatt; James O Hill; Brian G McGuckin; Carrie Brill; B Selma Mohammed; Philippe O Szapary; Daniel J Rader; Joel S Edman; Samuel Klein Journal: N Engl J Med Date: 2003-05-22 Impact factor: 91.245
Authors: Frank M Sacks; George A Bray; Vincent J Carey; Steven R Smith; Donna H Ryan; Stephen D Anton; Katherine McManus; Catherine M Champagne; Louise M Bishop; Nancy Laranjo; Meryl S Leboff; Jennifer C Rood; Lilian de Jonge; Frank L Greenway; Catherine M Loria; Eva Obarzanek; Donald A Williamson Journal: N Engl J Med Date: 2009-02-26 Impact factor: 91.245
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Jeffrey R O'Connell; Leena Peltonen; David Schlessinger; David P Strachan; Cornelia M van Duijn; H-Erich Wichmann; Timothy M Frayling; Unnur Thorsteinsdottir; Gonçalo R Abecasis; Inês Barroso; Michael Boehnke; Kari Stefansson; Kari E North; Mark I McCarthy; Joel N Hirschhorn; Erik Ingelsson; Ruth J F Loos Journal: Nat Genet Date: 2010-10-10 Impact factor: 38.330
Authors: Richa Saxena; Marie-France Hivert; Claudia Langenberg; Toshiko Tanaka; James S Pankow; Peter Vollenweider; Valeriya Lyssenko; Nabila Bouatia-Naji; Josée Dupuis; Anne U Jackson; W H Linda Kao; Man Li; Nicole L Glazer; Alisa K Manning; Jian'an Luan; Heather M Stringham; Inga Prokopenko; Toby Johnson; Niels Grarup; Trine W Boesgaard; Cécile Lecoeur; Peter Shrader; Jeffrey O'Connell; Erik Ingelsson; David J Couper; Kenneth Rice; Kijoung Song; Camilla H Andreasen; Christian Dina; Anna Köttgen; Olivier Le Bacquer; François Pattou; Jalal Taneera; Valgerdur Steinthorsdottir; Denis Rybin; Kristin Ardlie; Michael Sampson; Lu Qi; Mandy van Hoek; Michael N Weedon; Yurii S Aulchenko; Benjamin F Voight; Harald Grallert; Beverley Balkau; Richard N Bergman; Suzette J Bielinski; Amelie Bonnefond; Lori L Bonnycastle; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Thomas A Buchanan; Suzannah J Bumpstead; Christine Cavalcanti-Proença; Guillaume Charpentier; Yii-Der Ida Chen; Peter S Chines; Francis S Collins; Marilyn Cornelis; Gabriel J Crawford; Jerome Delplanque; Alex Doney; Josephine M Egan; Michael R Erdos; Mathieu Firmann; Nita G Forouhi; Caroline S Fox; Mark O Goodarzi; Jürgen Graessler; Aroon Hingorani; Bo Isomaa; Torben Jørgensen; Mika Kivimaki; Peter Kovacs; Knut Krohn; Meena Kumari; Torsten Lauritzen; Claire Lévy-Marchal; Vladimir Mayor; Jarred B McAteer; David Meyre; Braxton D Mitchell; Karen L Mohlke; Mario A Morken; Narisu Narisu; Colin N A Palmer; Ruth Pakyz; Laura Pascoe; Felicity Payne; Daniel Pearson; Wolfgang Rathmann; Annelli Sandbaek; Avan Aihie Sayer; Laura J Scott; Stephen J Sharp; Eric Sijbrands; Andrew Singleton; David S Siscovick; Nicholas L Smith; Thomas Sparsø; Amy J Swift; Holly Syddall; Gudmar Thorleifsson; Anke Tönjes; Tiinamaija Tuomi; Jaakko Tuomilehto; Timo T Valle; Gérard Waeber; Andrew Walley; Dawn M Waterworth; Eleftheria Zeggini; Jing Hua Zhao; Thomas Illig; H Erich Wichmann; James F Wilson; Cornelia van Duijn; Frank B Hu; Andrew D Morris; Timothy M Frayling; Andrew T Hattersley; Unnur Thorsteinsdottir; Kari Stefansson; Peter Nilsson; Ann-Christine Syvänen; Alan R Shuldiner; Mark Walker; Stefan R Bornstein; Peter Schwarz; Gordon H Williams; David M Nathan; Johanna Kuusisto; Markku Laakso; Cyrus Cooper; Michael Marmot; Luigi Ferrucci; Vincent Mooser; Michael Stumvoll; Ruth J F Loos; David Altshuler; Bruce M Psaty; Jerome I Rotter; Eric Boerwinkle; Torben Hansen; Oluf Pedersen; Jose C Florez; Mark I McCarthy; Michael Boehnke; Inês Barroso; Robert Sladek; Philippe Froguel; James B Meigs; Leif Groop; Nicholas J Wareham; Richard M Watanabe Journal: Nat Genet Date: 2010-01-17 Impact factor: 38.330
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