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Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study.

Accepted version
Peer-reviewed

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Type

Article

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Authors

van der Schouw, Yvonne T 
Imamura, Fumiaki 

Abstract

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 (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 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 (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 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.

Description

Keywords

Adult, Animals, Case-Control Studies, Cohort Studies, Dairy Products, Diabetes Mellitus, Type 2, Eating, Female, Gene-Environment Interaction, Genotype, Humans, Incidence, Lactase, Male, Mendelian Randomization Analysis, Middle Aged, Milk, Neoplasms, Nutrition Assessment, Polymorphism, Single Nucleotide, Risk Factors

Journal Title

Diabetes Care

Conference Name

Journal ISSN

0149-5992
1935-5548

Volume Title

Publisher

American Diabetes Association
Sponsorship
Medical Research Council (MC_UU_12015/5)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
European Commission (37197)
British Heart Foundation (None)
Medical Research Council (MC_UU_00002/7)
British Heart Foundation (RG/18/13/33946)
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (G0401527/1)
Cancer Research Uk (None)
NGF, FI, CL and NJW: MRC Epidemiology Unit core support (MC_UU_12015/5 and MC_UU_12015/1]; NGF and NJW: National Institute for Health Research Cambridge Biomedical Research Centre [IS-BRC-1215-20014];