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Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study

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Abstract

It is unclear whether vitamin D lowers risk of type 2 diabetes (T2D). In an observational study, we assessed the prospective association between plasma 25-hydroxyvitamin D (25(OH)D) and incident T2D, and evaluated whether it holds up for genetically determined elevated 25(OH)D. We used a case-cohort study nested within the German arm of the European Prospective Investigation into Cancer. From a total cohort of 53,088 participants with a mean follow-up of 6.6 years, we identified a random subcohort of 2,121 participants (57 % women) and 1,572 incident cases of T2D. 25(OH)D was measured in baseline plasma samples retrieved from frozen storage. Mean plasma 25(OH)D in the subcohort was 47.1 (5th–95th percentile 19.6–80.7) nmol/L. After controlling for age, sex, center, season of blood draw, education, and lifestyle, the hazard of T2D decreased across increasing plasma concentrations of 25(OH)D (P linear trend <0.0001). The association became non-linear after adjustment for BMI and waist circumference (P non-linearity <0.0001), with the inverse association being restricted to participants with 25(OH)D concentrations below ~45 nmol/L (hazard ratio per 5 nmol/L higher 25(OH)D 0.91, 95 % CI 0.84–0.98). A score predicting genetically determined plasma 25(OH)D by weighting four independent single-nucleotide polymorphisms by their effect on 25(OH)D, explained 3.7 % of the variance in 25(OH)D. The hazard ratio (95 % CI) per 5 nmol/L higher genetically predicted 25(OH)D was 0.98 (0.89–1.08) in the entire study sample and 1.06 (0.93–1.21) in the sub-sample with 25(OH)D <45 nmol/L. This latter finding casts doubt on a strong causal association of 25(OH)D with T2D, but further research in large-scale consortia is needed.

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Acknowledgments

This study was funded by the Federal Ministry of Education and Research, Germany (BMBF FKZ 01EA1323).

Conflict of interest

No potential conflicts of interest relevant to this article were reported. All researchers and authors were independent of the funding source. No funding source or sponsor was involved in the design or performance of the study; in the collection, management, analyses, or interpretation of the data; or in the preparation, review, approval, or decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany

    Brian Buijsse, Heiner Boeing, Cornelia Weikert & Marion Gottschald

  2. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    Matthias B. Schulze

  3. Institute of Agricultural and Nutritional Sciences, Human Nutrition, Martin-Luther-University Halle-Wittenberg, Halle, Germany

    Frank Hirche & Gabriele I. Stangl

  4. Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Jutta Dierkes

  5. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany

    Tilman Kühn, Verena A. Katzke, Birgit Teucher & Rudolf Kaaks

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  1. Brian Buijsse
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  2. Heiner Boeing
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Correspondence to Brian Buijsse.

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Online Resource 2

Seasonal variation in plasma 25(OH)D during the baseline measurement of participants in the subcohort of the EPIC-Germany Study. For clarity, two 25(OH)D values above 200 nmol/L were omitted from the figure. (BMP 2269 kb)

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Buijsse, B., Boeing, H., Hirche, F. et al. Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study. Eur J Epidemiol 28, 743–752 (2013). https://doi.org/10.1007/s10654-013-9844-5

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  • DOI: https://doi.org/10.1007/s10654-013-9844-5

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