Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double-blind placebo-controlled trial

Aims: To investigate the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes. Methods: In a double-blind placebo-controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100 000 IU vitamin D-2 (ergocalciferol) or 100 000 IU vitamin D-3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C-reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation. Results: The mean [standard deviation (s.d.)] 25-hydroxyvitamin D [25(OH)D](2) concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D-2 group, and the mean (s.d.) 25(OH)D-3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D-3 group. There was no effect of vitamin D supplementation on HbA1c: D-2 versus placebo: -0.05% [95% confidence interval (CI) -0.11, 0.02] or -0.51 mmol/mol (95% CI -1.16, 0.14; p=0.13); D-3 versus placebo: 0.02% (95% CI -0.04, 0.08) or 0.19 mmol/mol (95% CI -0.46, 0.83; p=0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D-2 versus placebo: -0.68 m/s (95% CI -1.31, -0.05); D-3 versus placebo -0.73 m/s (95% CI -1.42, -0.03)]. No important safety issues were identified. Conclusions: Short-term supplementation with vitamin D-2 or D-3 had no effect on HbA1c. The modest reduction in PWV with both D-2 and D-3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness.