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 Aug;55(8):2173-82. doi: 10.1007/s00125-012-2544-y. Epub 2012 Apr 15.


Aims/hypothesis: Epidemiological evidence is suggestive, but limited, for an association between circulating 25-hydroxyvitamin D (25[OH]D) and risk of type 2 diabetes. We conducted a systematic review and meta-analysis that included new data from previously unpublished studies.

Methods: Using a nested case-cohort design in the European Prospective Investigation into Cancer (EPIC)-Norfolk study, we identified a random subcohort and incident type 2 diabetes cases occurring between baseline (1993-1997) and 2006. In the Ely prospective study we identified incident type 2 diabetes cases between 1990 and 2003. We conducted a systematic review of prospective studies on 25(OH)D and type 2 diabetes published in MEDLINE or EMBASE until 31 January 2012, and performed a random-effects meta-analysis combining available evidence with results from the EPIC-Norfolk and Ely studies.

Results: In EPIC-Norfolk, baseline 25(OH)D was lower among incident type 2 diabetes cases (mean [SD] 61.6 [22.4] nmol/l; n=621) vs non-case subcohort participants (mean 65.3 [23.9] nmol/l; n=826). There was an inverse association between baseline 25(OH)D and incident type 2 diabetes in multivariable-adjusted analyses: HR (95% CI) 0.66 (0.45, 0.97), 0.53 (0.34, 0.82), 0.50 (0.32, 0.76), p trend <0.001, comparing consecutive increasing 25(OH)D quartiles with the lowest. In Ely, 37 incident type 2 diabetes cases were identified among 777 participants. In meta-analysis, the combined RR of type 2 diabetes comparing the highest with lowest quartile of 25(OH)D was 0.59 (0.52, 0.67), with little heterogeneity (I (2) =2.7%, p=0.42) between the 11 studies included (3,612 cases and 55,713 non-cases).

Conclusions/interpretation: These findings demonstrate an inverse association between circulating 25(OH)D and incident type 2 diabetes. However, causal inference should be addressed through adequately dosed randomised trials of vitamin D supplementation or genetic Mendelian randomisation experiments.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • England / epidemiology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • White People*


  • Vitamin D
  • 25-hydroxyvitamin D