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 KhawCecilie 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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

218 Downloads (Pure)

Abstract

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.

Original languageEnglish
JournalDiabetologia
Volume61
Issue number6
Pages (from-to)1325-1332
ISSN0012-186X
DOIs
Publication statusPublished - 2018

Keywords

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

Fingerprint Dive into the research topics of 'Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries'. Together they form a unique fingerprint.

Cite this