Intratrial Exposure to Vitamin D and New-Onset Diabetes

Intratrial Exposure to Vitamin D and New-Onset Diabetes Among Adults With Prediabetes: A Secondary Analysis From the Vitamin D and Type 2 Diabetes (D2d) Study

OBJECTIVE
Postrandomization biases may inﬂuence the estimate of efﬁcacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modiﬁed by trial assignment (vitamin D vs. placebo).

RESEARCH DESIGN AND METHODS
The D2d study compared the effect of daily supplementation with 100 mg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with pre- diabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of <50, 75–99, 100–124, and ‡125 nmol/L were compared with those with levels of 50–74 nmol/L (the range considered adequate by the National Academy of Medicine) in the entire cohort and by trial assignment.
RESULTS
There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P 5 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68–0.82) among those assigned to vitamin D and 0.90 (0.80–1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100–124 and ‡125 nmol/L were 0.48 (0.29– 0.80) and 0.29 (0.17–0.50), respectively, compared with those who maintained a level of 50–74 nmol/L.
CONCLUSIONS
Daily vitamin D supplementation to maintain a serum 25(OH)D level ‡100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.

Bess Dawson-Hughes,1
Myrlene A. Staten,2§ William C. Knowler,3 Jason Nelson,4 Ellen M. Vickery,5 Erin S. LeBlanc,6 Lisa M. Neff,7 Jean Park,8 and Anastassios G. Pittas,5 for the D2d Research Group Investigators*

1 Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 2 National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
3 National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ

4 Tufts Medical Center, Boston, MA
5 Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, MA 6 Kaiser Permanente Center for Health Research NW, Portland, OR 7 Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 8 MedStar Health Research Institute, Hyattsville, MD Corresponding author: Anastassios G. Pittas, apittas@tuftsmedicalcenter.org Received 14 July 2020 and accepted 16 September 2020 *A complete list of the D2d Research Group collaborators can be found in the APPENDIX. §Retired © 2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for proﬁt, and the work is not altered. More information is available athttps://www.diabetesjournals .org/content/license.

Diabetes Care Publish Ahead of Print, published online October 5, 2020