Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study
Vissers, Linda E.T.; Sluijs, Ivonne; van der Schouw, Yvonne T.; Forouhi, Nita G.; Imamura, Fumiaki; Burgess, Stephen; Barricarte, Aurelio; Boeing, Heiner; Bonet, Catalina; Chirlaque, Maria Dolores; Fagherazzi, Guy; Franks, Paul W.; Freisling, Heinz; Gunter, Marc J.; Ramón Quirós, J.; Ibsen, Daniel B.; Kaaks, Rudolf; Key, Timothy; Khaw, Kay T.; Kühn, Tilman; Mokoroa, Olatz; Nilsson, Peter M.; Overvad, Kim; Pala, Valeria; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Spijkerman, Annemieke M.W.; Tjonneland, Anne; Tumino, Rosario; Rodríguez-Barranco, Miguel; Rolandsson, Olov; Riboli, Elio; Sharp, Stephen J.; Langenberg, Claudia; Wareham, Nicholas J.
(2019) Diabetes Care, volume 42, issue 4, pp. 568 - 575
(Article)
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
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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.
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Keywords: Advanced and Specialised Nursing, Internal Medicine, Endocrinology, Diabetes and Metabolism, Journal Article
ISSN: 0149-5992
Publisher: American Diabetes Association Inc.
Note: Funding Information: Acknowledgments. The authors thank all EPIC participants and staff for their contribution to the study. The authors thank Nicola Kerrison (MRC Epidemiology Unit) for managing the data for the InterAct project. The authors thank staff from the Technical, Field Epidemiology, and Data Functional Group Teams of the MRC Epidemiology Unit for carrying out sample preparation, DNA provision and quality control, genotyping, and data-handling work. The authors specifically thank S. Dawson for coordinating the sample provision for biomarker measurements; A. Britten for coordinating DNA sample provision and genotyping of candidate markers; N. Kerrison, C. Gillson, and A. Britten for data provision and genotyping quality control; and M. Sims for writing the technical laboratory specification for the intermediate pathway biomarker measurements and for overseeing the laboratory work. Funding. Funding for the InterAct project was provided by the European Union Sixth Framework Programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: for N.G.F., F.I., C.L., and N.J.W., MRC Epidemiology Unit core support (MC_UU_12015/5 and MC_UU_12015/1), and for N.G.F. and N.J.W., National Institute for Health Research Cambridge Biomedical Research Centre (IS-BRC-1215-20014). Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of University Medical Center Utrecht (the Netherlands) (to I.S. and Y.T.v.d.S.). P.W.F. acknowledges funding from the Swedish Research Council, the Swedish Heart Lung Foundation, and the Swedish Diabetes Association. J.R.Q. acknowledges funding from the Asturias Regional Government. R.K. acknowledges funding from Deutsche Krebshilfe. T.Ke. acknowledges funding from the U.K. Medical Research Council (MR/M012190/1) and the Wellcome Trust Our Planet, Our Health (Livestock, Environment and People [LEAP 205212/Z/16/Z]). S.P. acknowledges funding from Associazione Italiana per la Ricerca sul Cancro. A.M.W.S. acknowledges funding from the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, and Statistics Netherlands (the Netherlands). K.O. and A.T. acknowledge funding from the Danish Cancer Society. R.T. acknowledges funding from AIRE-ONLUS Ragusa, AVIS-Ragusa, and the Sicilian Regional Government. Duality of Interest. P.W.F. acknowledges funding from Novo Nordisk. No other potential conflicts of interest relevant to this article were reported. Author Contributions. L.E.T.V. analyzed data and drafted the manuscript. L.E.T.V., I.S., and Y.T.v.d.S. had access to all data for this study. All authors contributed to study conception and design, interpretation of data, critical revision of the manuscript for important intellectual content, and final approval of the version to be published. L.E.T.V. and I.S. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the Mendelian Randomization Conference, Bristol, U.K., 11–13 July 2017, and the European Society of Cardiology Congress, Barcelona, Spain, 26–30 August 2017. Publisher Copyright: © 2019 by the American Diabetes Association.
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