Abstract
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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01463813.