DIABETES MELLITUS

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 BuijsseAffiliated withDepartment of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke Email author 
  • , Heiner BoeingAffiliated withDepartment of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke
  • , Frank HircheAffiliated withInstitute of Agricultural and Nutritional Sciences, Human Nutrition, Martin-Luther-University Halle-Wittenberg
  • , Cornelia WeikertAffiliated withDepartment of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke
  • , Matthias B. SchulzeAffiliated withDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke
  • , Marion GottschaldAffiliated withDepartment of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke
  • , Tilman KühnAffiliated withDivision of Cancer Epidemiology, German Cancer Research Center
  • , Verena A. KatzkeAffiliated withDivision of Cancer Epidemiology, German Cancer Research Center
  • , Birgit TeucherAffiliated withDivision of Cancer Epidemiology, German Cancer Research Center
    • , Jutta DierkesAffiliated withDepartment of Clinical Medicine, University of Bergen
    • , Gabriele I. StanglAffiliated withInstitute of Agricultural and Nutritional Sciences, Human Nutrition, Martin-Luther-University Halle-Wittenberg
    • , Rudolf KaaksAffiliated withDivision of Cancer Epidemiology, German Cancer Research Center

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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.

Keywords

Vitamin D Type 2 diabetes Single-nucleotide polymorphism Prospective study