Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study
- First Online:
- 487 Downloads
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.
KeywordsVitamin D Type 2 diabetes Single-nucleotide polymorphism Prospective study
- 7.Alvarez JA, Ashraf A. Role of vitamin d in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol. 2009;2010:351385.Google Scholar
- 10.Forouhi NG, Ye Z, Rickard AP, et al. Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. Diabetologia. 2012;55(8):2173–82.PubMedCrossRefGoogle Scholar
- 11.Afzal S, Bojesen SE, Nordestgaard BG. Low 25-Hydroxyvitamin D and Risk of Type 2 Diabetes: A Prospective Cohort Study and Meta-analysis. Clin Chem. 2012;59(2):381–91.Google Scholar
- 14.World Climate Guide. Germany Climate Guides. Source: http://www.worldclimateguide.co.uk/climateguides/germany/ (Accessed January 2, 2013).
- 15.di Giuseppe R, Hirche F, Montonen J, et al. Reliability of plasma fibroblast growth factor 23 as risk biomarker in epidemiological studies measured over a four-month period. Ann Clin Biochem. 2012;49(Pt 6):542-5.Google Scholar
- 19.Wie wird ein Vitamin-D-Mangel festgestellt? Robert Koch Institute. Source:http://www.rki.de/SharedDocs/FAQ/vitamind3/vitamind3.html. (Accessed January 31, 2013).
- 20.Royston P, Sauerbrei W. Multivariable model-builing: a pragmatic approach to regression analysis based on fractional polynomials for modelling continuous variables. Chichester: Wiley; 2008.Google Scholar
- 25.Gagnon C, Lu ZX, Magliano DJ, et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study). Diabetes Care. 2011;34(5):1133–8.PubMedCrossRefGoogle Scholar
- 27.Husemoen LL, Skaaby T, Thuesen BH, Jorgensen T, Fenger RV, Linneberg A. Serum 25(OH)D and incident type 2 diabetes: a cohort study. Eur J Clin Nutr. 2012;66(12):1309–14. Google Scholar
- 28.Schottker B, Herder C, Rothenbacher D, Perna L, Muller H, Brenner H. Serum 25-hydroxyvitamin D levels and incident diabetes mellitus type 2: a competing risk analysis in a large population-based cohort of older adults. Eur J Epidemiol. 2013. doi 10.1007/s10654-013-9769-z.
- 29.Jorde R, Schirmer H, Wilsgaard T, et al. Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromso Study. PLoS ONE. 2012;7(5):e37295.Google Scholar