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Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

Journal article
Authors Sherly X Li
Fumiaki Imamura
Matthias B Schulze
Jusheng Zheng
Zheng Ye
Antonio Agudo
Eva Ardanaz
Dagfinn Aune
Heiner Boeing
Miren Dorronsoro
Courtney Dow
Guy Fagherazzi
Sara Grioni
Marc J Gunter
José María Huerta
Daniel B Ibsen
Marianne Uhre Jakobsen
Rudolf Kaaks
Timothy J Key
Kay-Tee Khaw
Cecilie Kyrø
Francesca Romana Mancini
Elena Molina-Portillo
Neil Murphy
Peter M Nilsson
N Charlotte Onland-Moret
Domenico Palli
Salvatore Panico
Alaitz Poveda
J Ramón Quirós
Fulvio Ricceri
Ivonne Sluijs
Annemieke M W Spijkerman
Anne Tjonneland
Rosario Tumino
Anna Winkvist
Claudia Langenberg
Stephen J Sharp
Elio Riboli
Robert A Scott
Nita G Forouhi
Nicholas J Wareham
Published in Diabetologia
Volume 61
Issue 6
Pages 1325-1332
ISSN 1432-0428
Publication year 2018
Published at Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 1325-1332
Language en
Keywords Adult, Alleles, Body Mass Index, Diabetes Mellitus, Type 2, epidemiology, genetics, Diet, Dietary Fiber, Energy Intake, Europe, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Insulin Resistance, International Cooperation, Male, Middle Aged, Nutrients, administration & dosage, Nutrition Assessment, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Surveys and Questionnaires
Subject categories Public Health, Global Health, Social Medicine and Epidemiology, Nutrition and Dietetics


Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution.No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined.Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

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