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

N G Forouhi, R K Menon, S J Sharp, N Mannan, P M Timms, A R Martineau, A P Rickard, B J Boucher, T A Chowdhury, C J Griffiths, S E Greenwald, S J Griffin, G A Hitman

Although an inverse association between 25-hydroxyvitamin D [25(OH)D] concentration and type 2 diabetes and coronary risk exists, a causal link has not been established. We investigated the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals at increased diabetes risk. In a double-blind placebo-controlled randomised trial, 340 adults at increased type 2 diabetes risk (non-diabetic hyperglycaemia or positive diabetes risk score) were randomised to either placebo, 100,000 IU Vitamin D2 (ergocalciferol) or 100,000 IU Vitamin D3 (cholecalciferol), orally administered monthly for four months. The primary outcome was change in glycated haemoglobin (HbA1c ) between baseline and four months, adjusted for baseline. Secondary outcomes included: blood pressure, lipids, apolipoproteins, C-reactive protein, pulse wave velocity (PWV), anthropometric measures and safety of supplementation. Mean (SD) 25(OH)D2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in D2 group, and 25(OH)D3 from 45.8 (22.6) to 83.8 (22.7) nmol/l in D3 . There was no effect of vitamin D supplementation on HbA1c : D2 versus placebo: -0.51 (-1.16, 0.14) mmol/mol;p = 0.13; [-0.05% (95%CI -0.11%, 0.02%)]; D3 versus placebo: 0.19 (-0.46, 0.83) mmol/mol;p = 0.57; [0.02% (-0.04%, 0.08%)]. There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo:-0.68 (-1.31, -0.05) m/s; D3 versus placebo -0.73 (-1.42, -0.03) m/s]. No important safety issues were identified. Short-term supplementation with vitamin D2 or D3 had no effect on HbA1c . The modest reduction in PWV with both D2 and D3 relative to placebo suggests a beneficial effect of vitamin D supplementation on arterial stiffness.