558-P: Effect of Vitamin D Supplementation on Regression to Normal Glucose Regulation from Prediabetes in the D2d Study

Regression to normal glucose regulation (NGR) has been reported in response to lifestyle modification and medications. In this secondary analysis of the D2d study, a randomized trial of 4,000 IU/d of vitamin D₃ vs. placebo, we determined whether vitamin D increased regression to NGR in people with prediabetes. Eligible participants met at least 2-of-3 ADA glycemic criteria for prediabetes (n=2423) and the two groups were similar at baseline. During follow-up, glycemic status was assessed semi-annually with FG and HbA1c and annually with 2-hour glucose after 75-g glucose load (2hPG) . In exploratory analyses that censored follow up at initiation of diabetes/weight-loss medication, stopping trial pills, taking vitamin D above the trial limit, death or withdrawal, we tested for an effect of vitamin D on new-onset NGR, which was defined as the first occurrence of 2 or 3 glycemic criteria in the normal range and none in the diabetes range. Over a median follow-up of 2.5 years, the NGR outcome occurred in 343/12 participants in the vitamin D group and 295/1212 in the placebo group; hazard ratio (95%CI) for time-to-NGR for vitamin D was 1.16 (0.99-1.36) . Among those who never met NGR during follow-up (n=1785) , 29% developed diabetes compared to 8.2% among those who met NGR at some point during the study (p<0.01) . At the last encounter, the NGR outcome was observed in 133/1069 participants in the vitamin D group and 102/1050 in the placebo group; incidence rate ratio (95%CI) for vitamin D was 1.26 (0.97-1.63) . When we used the NGR definition from other studies to include only those with normal FG and 2hPG regardless of HbA1c, 90/1037 participants in the vitamin D group and 63/1050 in the placebo group at the last encounter had NGR; incidence rate ratio (95%CI) for vitamin D 1.39 (1.01-1.91) .

In conclusion, vitamin D supplementation increased the likelihood of regression to NGR at the last visit, and those who met NGR during the study were less likely to subsequently develop diabetes.