The effect of vitamin D3 supplementation on the incidence of type 2 diabetes in healthy older adults not at high risk for diabetes (FIND): a randomised controlled trial

Aims/hypothesis Vitamin D insufficiency is associated with an elevated risk of type 2 diabetes, but evidence from randomised trials on the benefits of vitamin D supplementation is limited, especially for average-risk populations. The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D-3 supplementation at two different doses on the incidence of type 2 diabetes in a generally healthy older adult population. Methods FIND was a 5 year randomised placebo-controlled, parallel-arm trial among 2271 male and female participants aged >= 60 years and >= 65 years, respectively, from a general Finnish population who were free of CVD or cancer and did not use diabetes medications. The study had three arms: placebo, 1600 IU/day of vitamin D-3 or 3200 IU/day of vitamin D-3. A non-study group statistician carried out sex-stratified simple randomisation in a 1:1:1 ratio, based on computerised random number generation. The participants, investigators and study staff were masked to group assignment. National health registries were used to collect event data. A representative subcohort of 505 participants had more detailed in-person investigations at months 0, 6, 12 and 24. Results During the mean follow-up of 4.2 years, there were 38 (5.0%), 31 (4.2%) and 36 (4.7%) type 2 diabetes events in the placebo (n=760), 1600 IU/day vitamin D-3 (n=744; vs placebo: HR 0.81; 95% CI 0.50, 1.30) and 3200 IU/day vitamin D-3 (n=767; vs placebo: HR 0.92, 95% CI 0.58, 1.45) arms, respectively (p-trend=0.73). When the two vitamin D-3 arms were combined and compared with the placebo arm, the HR was 0.86 (95% CI 0.58, 1.29). In the analyses stratified by BMI (<25 kg/m(2) [n=813, number of type 2 diabetes events=12], 25-30 kg/m(2) [n=1032, number of events=38], >= 30 kg/m(2) [n=422, number of events=54]), the HRs in the combined vitamin D-3 arms vs the placebo were 0.43 (95% CI 0.14, 1.34), 0.97 (0.50, 1.91) and 1.00 (0.57, 1.75), respectively (p-interaction <0.001). In the subcohort, the mean (SD) baseline serum 25-hydroxyvitamin D-3 (25(OH)D-3) concentration was 74.5 (18.1) nmol/l. After 12 months, the concentrations were 72.6 (17.7), 99.3 (20.8) and 120.9 (22.1) nmol/l in the placebo, 1600 IU/day vitamin D-3 and 3200 IU/day vitamin D-3 arms, respectively. In the subcohort, no differences were observed in changes in plasma glucose or insulin concentrations, BMI or waist circumference during the 24 month follow-up (p values >= 0.19). Conclusion/interpretation Among generally healthy older adults who are not at high risk for diabetes and who have serum 25(OH)D-3 levels that are sufficient for bone health, vitamin D-3 supplementation did not significantly reduce the risk of developing diabetes.