The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study

J Diabetes Complications. 2022 Aug;36(8):108230. doi: 10.1016/j.jdiacomp.2022.108230. Epub 2022 Jun 12.


Aims: Low blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes.

Methods: 2423 participants were randomized to 4000 IU/day of vitamin D3 or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE.

Results: Mean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (-0.45 %, 95%CI -0.75 to -0.15).

Conclusions: In people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score.

Trial registration: D2d number, NCT01942694, prospectively registered September 16, 2013.

Keywords: Cardiovascular disease risk reduction; MACE; Prediabetes; Vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Middle Aged
  • Prediabetic State* / complications
  • Prediabetic State* / drug therapy
  • Prediabetic State* / epidemiology
  • Risk Factors
  • Vitamin D / therapeutic use
  • Vitamins / therapeutic use


  • Vitamins
  • Vitamin D

Associated data