Dairy product intake and risk of type 2 diabetes in EPIC-interact: A mendelian randomization study

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OBJECTIVE To estimate the causal association between intake of dairy products and incident type 2 diabetes. RESEARCH DESIGN AND METHODS The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. RESULTS Each additional LP allele was associated with a higher intake of milk (b 17.1 g/day, 95% CI 10.6–23.6) and milk beverages (b 2.8 g/day, 95% CI 1.0–4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (b 27.0 g/day, 95% CI 212.4 to 21.7 per additional LP allele), nonalcoholic beverages (b 218.0 g/day, 95% CI 234.4 to 21.6), and wine (b 24.8 g/day, 95% CI 29.1 to 20.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratio per 15 g/day 0.99, 95% CI 0.93–1.05). CONCLUSIONS rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.


  • Linda E.T. Vissers
  • Ivonne Sluijs
  • Yvonne T. van der Schouw
  • Nita G. Forouhi
  • Fumiaki Imamura
  • Stephen Burgess
  • Aurelio Barricarte
  • Heiner Boeing
  • Catalina Bonet
  • Maria Dolores Chirlaque
  • Guy Fagherazzi
  • Heinz Freisling
  • Marc J. Gunter
  • J. Ramón Quirós
  • Daniel B. Ibsen
  • Rudolf Kaaks
  • Timothy Key
  • Kay T. Khaw
  • Tilman Kühn
  • Olatz Mokoroa
  • Kim Overvad
  • Valeria Pala
  • Domenico Palli
  • Salvatore Panico
  • Carlotta Sacerdote
  • Annemieke M.W. Spijkerman
  • Anne Tjonneland
  • Rosario Tumino
  • Miguel Rodríguez-Barranco
  • Olov Rolandsson
  • Elio Riboli
  • Stephen J. Sharp
  • Claudia Langenberg
  • Nicholas J. Wareham
External organisations
  • University Medical Center Utrecht
  • University of Cambridge
  • Navarre Public Health Institute
  • German Institute of Human Nutrition
  • Catalan Institute of Oncology
  • University of Murcia
  • Centre for Research in Epidemiology and Population Health (CESP)
  • International Agency for Research on Cancer, World Health Organization
  • Public Health Directorate
  • Aarhus University
  • German Cancer Research Centre
  • University of Oxford
  • Aalborg University
  • Istituto Nazionale dei Tumori
  • University of Naples Federico II
  • Citta' della Salute e della Scienza Hospital-University of Turin
  • National Institute for Public Health and the Environment (RIVM)
  • Danish Cancer Society Research Center
  • Azienda Sanitaria Provinciale di Ragusa
  • Umeå University
  • Imperial College London
  • Utrecht University
  • Murcia Regional Health Council
  • Institut Gustave Roussy
  • University of Paris-Sud
  • Biodonostia Health Research Institute
  • Institute for Cancer Research, Prevention and Clinical Network (ISPRO)
  • University of Turin
  • University of Granada
  • Hospital Clínico Universitario San Cecilio
  • CIBER Epidemiology and Public Health (CIBERESP)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Public Health, Global Health, Social Medicine and Epidemiology
Original languageEnglish
Pages (from-to)568-575
Number of pages8
JournalDiabetes Care
Issue number4
Publication statusPublished - 2019
Publication categoryResearch