Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis.

BACKGROUND Vitamin D deficiency has been implicated in decreased insulin secretion and increased insulin resistance, hallmarks of type 2 diabetes mellitus. We tested the hypothesis that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with increased risk of type 2 diabetes in the general population. METHODS We measured 25(OH)D in 9841 participants from the general population, of whom 810 developed type 2 diabetes during 29 years of follow-up. Analyses were adjusted for sex, age, smoking status, body mass index, income, physical activity, HDL cholesterol, and calendar month of blood draw. RESULTS Lower 25(OH)D concentrations, by clinical categories or seasonally adjusted quartiles, were associated with higher cumulative incidence of type 2 diabetes (trend, P = 2×10(-7) and P = 4×10(-10)). Multivariable adjusted hazard ratios of type 2 diabetes were 1.22 (95% CI 0.85-1.74) for 25(OH)D <5 vs ≥20 μg/L and 1.35 (1.09-1.66) for lowest vs highest quartile. Also, the multivariable adjusted hazard ratio of type 2 diabetes for a 50% lower concentration of 25(OH)D was 1.12 (1.03-1.21); the corresponding hazard ratio for those ≤58 years old was 1.26 (1.15-1.41). Finally, in a metaanalysis of 16 studies, the odds ratio for type 2 diabetes was 1.50 (1.33-1.70) for the bottom vs top quartile of 25(OH)D. CONCLUSIONS We observed an association of low plasma 25(OH)D with increased risk of type 2 diabetes. This finding was substantiated in a metaanalysis.