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

Authors: DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; STATEN, MYRLENE - National Institute Of Diabetes And Digestive And Kidney Diseases; KNOWLER, WILLIAM - National Institute Of Diabetes And Digestive And Kidney Diseases; NELSON, JASON - Tufts Medical Center; VICKERY, ELLEN - Tufts Medical Center; LEBLANC, ERIN - Kaiser Permanente Center For Health Research; NEFF, LISA - Northwestern University; PARK, JEAN - Medstar Research Institute; PITTAS, ANASTASSIOS - Tufts Medical Center

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/16/2020
Publication Date: 10/5/2020
Citation: Dawson-Hughes, B., Staten, M.A., Knowler, W.C., Nelson, J., Vickery, E.M., LeBlanc, E.S., Neff, L.M., Park, J., Pittas, A.G. 2020. 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. Diabetes Care. https://doi.org/10.2337/dc20-1765.
DOI: https://doi.org/10.2337/dc20-1765

Interpretive Summary: Vitamin D insufficiency in adults has increased the risk of developing type two diabetes (T2D), but the optimal level of vitamin D needed to protect against T2D has not been defined. We examined the incidence of T2D in relation to the blood level of vitamin D during a clinical trial in which 2,158 adults at risk for diabetes were treated for 2.5 years with either 4000 IU per day of vitamin D or placebo. Overall, the risk of developing T2D was lower in participants with higher vitamin D levels (25-hydroxyvitamin D levels of 40 ng/ml and higher) than in participants with lower levels (20-30 ng/ml). This suggests that maintaining a blood 25(OH)D level of >=40 ng/ml is a promising approach to reducing risk of T2D in adults at high risk for diabetes, and it provides the rationale to conduct a clinical trial designed to test this possibility.

Technical Abstract: 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 micro g (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. 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 = 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.