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 x 10(-7) and P = 4 x 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 mu g/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. (C) 2012 American Association for Clinical Chemistry