European Journal of Epidemiology

, Volume 28, Issue 9, pp 743–752

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

  • Brian Buijsse
  • Heiner Boeing
  • Frank Hirche
  • Cornelia Weikert
  • Matthias B. Schulze
  • Marion Gottschald
  • Tilman Kühn
  • Verena A. Katzke
  • Birgit Teucher
  • Jutta Dierkes
  • Gabriele I. Stangl
  • Rudolf Kaaks
DIABETES MELLITUS

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.

Keywords

Vitamin D Type 2 diabetes Single-nucleotide polymorphism Prospective study 

Supplementary material

10654_2013_9844_MOESM1_ESM.doc (56 kb)
Online Resources 1 and 3(DOC 56 kb)
10654_2013_9844_MOESM2_ESM.bmp (2.2 mb)
Online Resource 2Seasonal 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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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Brian Buijsse
    • 1
  • Heiner Boeing
    • 1
  • Frank Hirche
    • 3
  • Cornelia Weikert
    • 1
  • Matthias B. Schulze
    • 2
  • Marion Gottschald
    • 1
  • Tilman Kühn
    • 5
  • Verena A. Katzke
    • 5
  • Birgit Teucher
    • 5
  • Jutta Dierkes
    • 4
  • Gabriele I. Stangl
    • 3
  • Rudolf Kaaks
    • 5
  1. 1.Department of EpidemiologyGerman Institute of Human Nutrition Potsdam-RehbrueckeNuthetalGermany
  2. 2.Department of Molecular EpidemiologyGerman Institute of Human Nutrition Potsdam-RehbrueckeNuthetalGermany
  3. 3.Institute of Agricultural and Nutritional Sciences, Human NutritionMartin-Luther-University Halle-WittenbergHalleGermany
  4. 4.Department of Clinical MedicineUniversity of BergenBergenNorway
  5. 5.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany

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