ABSTRACT: Observational and intervention studies have revealed inconsistent findings with respect to the relationship between vitamin D and insulin resistance. No intervention studies have been conducted in community samples whereas this may be particularly relevant to the primary prevention of type 2 diabetes (T2D) and cardiovascular disease (CVD). In the present study we examined whether temporal improvements in vitamin D status, measured as serum 25-hydroxyvitamin D [25(OH)D], reduce the risk of insulin resistance among individuals without T2D. We accessed and analyzed data from 5730 nondiabetic participants with repeated measures of serum 25(OH)D who enrolled in a preventive health program. We used the homeostatic model assessment for insulin resistance (HOMA-IR) and applied logistic regression to quantify the independent contribution of baseline serum 25(OH)D and temporal increases in 25(OH)D on HOMA-IR. The median time between baseline and follow up was 1.1 year. On average serum 25(OH)D concentrations increased from 89 nanomoles per liter (nmol/L) at baseline to 122 nmol/L at follow up. Univariate analyses showed that relative to participants with baseline serum 25(OH)D less than 50 nmol/L, participants with baseline concentrations of "50-<75", "75-<100", "100-<125", and ≥125 nmol/L were 0.76 (95% confidence intervals: 0.61-0.95), 0.54 (0.43-0.69), 0.48 (0.36-0.64) and 0.36 (0.27-0.49) times as likely to have insulin resistance at follow up, respectively. More importantly, relative to participants without temporal increases in 25(OH)D, those with increases in serum 25(OH)D of "<25", "25-<50", "50-<75", "≥75" nmol/L were 0.92 (0.72-1.17), 0.86 (0.65-1.13), 0.66 (0.47-0.93), and 0.74 (0.55-0.99) times as likely to have insulin resistance at follow up, respectively. In the subgroup of participants without insulin resistance at baseline, this was 0.96 (0.72-1.27), 0.78 (0.56-1.10), 0.66 (0.44-0.99), and 0.67 (0.48-0.94), respectively. These observations suggest that improvements in vitamin D status reduce the risk for insulin resistance and herewith may contribute to the primary prevention of T2D and CVD.
