A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial

Randomized, double-blind, placebo-controlled trial in adults with type 2 diabetes mellitus and hypovitaminosis D at a single tertiary centre in Singapore. The active vitamin D arm included 33 participants randomized in a 1:1 allocation to cholecalciferol versus placebo.

In the active arm, participants received oral cholecalciferol for 16 weeks using a targeted dosing strategy based on baseline 25(OH)D: 4000 IU daily if baseline 25(OH)D was ≤20 ng/mL, or 2000 IU daily if baseline 25(OH)D was 21-30 ng/mL. At 8 weeks, the dose was reduced by half if 25(OH)D had risen above 30 ng/mL. The regimen was compared with placebo in a randomized, double-blind trial.

Targeted vitamin D repletion raised 25(OH)D to the intended range but did not produce a statistically significant improvement in the primary endothelial function outcome after adjustment. Reactive hyperemia index increased within the vitamin D arm from 0.65 (0.42) to 0.73 (0.36), but the between-group result was not significant after adjustment (p = 0.07), despite an unadjusted p = 0.02. Mean 25(OH)D rose from 17.3 ± 5.2 ng/mL at baseline to 31.3 ± 9.0 ng/mL at 8 weeks and 31.6 ± 9.5 ng/mL at 16 weeks; 16/33 (49%) achieved >30 ng/mL at 8 weeks and 23/33 (70%) at 16 weeks. Other vascular/inflammatory markers, including AIx, E-selectin, vWF, and hsCRP, were not meaningfully improved, and no patient developed hypercalcaemia.

The trial was relatively small, single-centre, and short duration, which limits power to detect modest cardiovascular effects. The primary endpoint was not significant after adjustment, and the observed biomarker changes were small, making clinical relevance uncertain. Generalizability is limited to a multi-ethnic Singaporean type 2 diabetes population with vitamin D insufficiency.