Abstract
BACKGROUND: Evidence on whether the association between vitamin D levels and diabetes risk differs across glycemic statuses is limited. We investigated the association between circulating vitamin D levels and type 2 diabetes risk according to glycemic status. METHODS: This prospective cohort study included 3604 participants without diabetes (mean age: 56 years) whose serum 25-hydroxyvitamin D (25(OH)D) levels were measured in the community-based Korean Genome Epidemiology Study (2007-2009). Fasting and 2-h post-load glucose and glycated hemoglobin (HbA1c) levels were measured biannually over a 14-year follow-up period. Season-standardized serum 25(OH)D levels were categorized into <25 (deficient), 25-50 (insufficient), and ≥ 50 nmol/L (sufficient). We assessed the association between serum 25(OH)D levels and type 2 diabetes risk using Cox proportional hazards models with time-varying covariates, stratifying by glycemic status and individual glycemic markers. RESULTS: Over 43,176 person-years of follow-up, 796 participants developed type 2 diabetes. Compared with participants with vitamin D deficiency, the multivariable-adjusted hazard ratios (95% confidence intervals) for type 2 diabetes in those with vitamin D sufficiency were 0.80 (0.62-1.04) overall, 0.55 (0.32-0.97) in participants with normoglycemia, and 0.93 (0.69-1.24) in those with prediabetes (P for interaction by glycemic status = 0.04). The association between serum 25(OH)D levels and diabetes risk differed according to HbA1c level (P for interaction = 0.05); a trend toward a lower risk of type 2 diabetes was observed in participants with HbA1c < 5.7% but not in those with HbA1c 5.7-6.4%. CONCLUSIONS: The association between serum 25(OH)D levels and the risk of type 2 diabetes differed by glycemic status, with a more pronounced inverse association among participants with normoglycemia.