Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study

Am J Clin Nutr. 2023 Jul;118(1):59-67. doi: 10.1016/j.ajcnut.2023.03.021. Epub 2023 Mar 29.


Background: Higher serum 25-hydroxyvitamin D [25(OH)D] is associated with lower type 2 diabetes risk. 25(OH)D varies due to skin pigmentation and weight.

Objectives: This analysis aims to determine whether the effect of vitamin D differs among people of color and those with overweight/obesity (who have higher diabetes risk) compared with individuals who are White or have normal weight.

Methods: The D2d study is a randomized clinical trial in people with prediabetes that tested the effects of daily vitamin D3 4000 IU vs. placebo on diabetes risk (median followup 2.5 y). We compared baseline and intratrial mean 25(OH)D concentrations, defined as the mean of all available annual 25(OH)D values, among groups defined by self-reported race and body mass index (BMI). We used Cox proportional hazards models to assess the associations between intratrial mean 25(OH)D and diabetes risk by race- and BMI-based groups.

Results: Asian (n=130), Black (n=616), and White (n=1616) participants were included. Both baseline and intratrial mean 25(OH)D concentrations differed significantly by race groups (both P < 0.001) and were lower in Asian and Black vs. White participants, and in those with higher vs. lower BMI adjusted for race (both P < 0.001). Compared with those with lower concentrations, Black and White participants with intratrial mean 25(OH)D ≥ 40 ng/mL had significantly reduced diabetes risk [HR (95% CI): Black: 0.51 (0.29, 0.92); White: 0.42 (0.30, 0.60)] and with a similar reduction in diabetes risk among Asian participants: 0.39 (0.14, 1.11). Compared with those with lower concentrations, participants with baseline BMI < 40 kg/m2 who achieved intratrial mean 25(OH)D concentrations ≥ 40 ng/mL had a significantly reduced diabetes risk. There was no statistically significant interaction between intratrial 25(OH)D and race or between intratrial 25(OH)D and BMI on diabetes risk.

Conclusions: Among people with prediabetes, particularly for Black and White race groups and those with BMI < 40 kg/m2, the optimal 25(OH)D concentration may be ≥ 40 ng/mL to optimize diabetes-prevention efforts. This trial was registered at clinicaltrials.gov as NCT01942694.

Keywords: blood 25(OH)D; body mass index (BMI); diabetes prevention; diabetes risk; race; vitamin D supplementation.

Publication types

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

MeSH terms

  • Diabetes Mellitus, Type 2*
  • Dietary Supplements
  • Humans
  • Prediabetic State* / complications
  • Vitamin D
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / drug therapy


  • 25-hydroxyvitamin D
  • Vitamin D

Associated data

  • ClinicalTrials.gov/NCT01942694