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

  • 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
Publishing year: 2018-03-17
Language: English
Pages: 1325-1332
Publication/Series: Diabetologia
Volume: 61
Issue: 6
Document type: Journal article
Publisher: Springer

Abstract english

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.


  • Endocrinology and Diabetes
  • BMI
  • Body mass index
  • Diabetes
  • Diet
  • Dietary fibre
  • Genetic risk score
  • GRS
  • Insulin resistance
  • Interaction
  • Macronutrient


  • Internal Medicine - Epidemiology
  • Genetic and Molecular Epidemiology
  • ISSN: 0012-186X
E-mail: alaitz [dot] poveda [dot] 6461 [at] med [dot] lu [dot] se

Postdoctoral fellow

Genetic and Molecular Epidemiology

+46 40 39 10 32

CRC 60-13-024


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00