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.
D.S.Hsia: None. A.G.Pittas: None. D2d research group: n/a. J.P.Nelson: None. E.Vickery: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. E.S.Leblanc: n/a. S.H.Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. I.Brodsky: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Dawson-hughes: None.
American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)