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

Research output: Contribution to journalArticle


Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.


  • 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
  • N. Charlotte Onland-Moret
  • Domenico Palli
  • Salvatore Panico
  • 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
External organisations
  • University of Cambridge
  • German Institute of Human Nutrition
  • German Center for Diabetes Research
  • Catalan Institute of Oncology
  • Health Research Institute of Navarra (IDISNA)
  • CIBER Epidemiology and Public Health (CIBERESP)
  • Imperial College London
  • Bjørknes University College
  • Public Health Division of Gipuzkoa
  • Istituto Nazionale dei Tumori
  • International Agency for Research on Cancer, World Health Organization
  • Murcia Regional Health Council
  • Aarhus University
  • Technical University of Denmark
  • German Cancer Research Centre
  • University of Oxford
  • Danish Cancer Society Research Center
  • University of Granada
  • University Medical Center Utrecht
  • Cancer Research and Prevention Institute (ISPO)
  • University of Naples Federico II
  • Umeå University
  • Skåne University Hospital
  • National Institute for Public Health and the Environment (RIVM)
  • Biodonostia Health Research Institute
  • University of Paris-Sud
  • Versailles Saint-Quentin-en-Yvelines University
  • Public Health Directorate
  • University of Turin
  • Civic and M.P Arezzo Hospital
  • Associazione Iblea per la Ricerca Epidemiologica
  • University of Gothenburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • BMI, Body mass index, Diabetes, Diet, Dietary fibre, Genetic risk score, GRS, Insulin resistance, Interaction, Macronutrient
Original languageEnglish
Pages (from-to)1325-1332
Issue number6
Early online date2018 Mar 17
Publication statusPublished - 2018
Publication categoryResearch