Effect of vitamin D supplementation on glycemia: a secondary analysis from the vitamin D and type 2 diabetes (D2d) study

Authors: HSIA, DANIEL - Pennington Biomedical Research Center; NELSON, JASON - Tufts Medical Center; VICKERY, ELLEN - Tufts Medical Center; RASOULI, NEDA - University Of Colorado; LEBLANC, ERIN - Kaiser Permanente; KIM, SUN - Stanford University; BRODSKY, IRWIN - Maine Medical Center; PRATLEY, RICHARD - Adventhealth Translational Research Institute For Metabolism And Diabetes; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PITTAS, ANASTASSIOS - Tufts Medical Center

Submitted to: Diabetes Research and Clinical Practice
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/14/2023
Publication Date: 8/1/2023
Citation: Hsia, D.S., Nelson, J., Vickery, E.M., Rasouli, N., LeBlanc, E.S., Kim, S., Brodsky, I., Pratley, R., Dawson-Hughes, B., Pittas, A.G. 2023. Effect of vitamin D supplementation on glycemia: a secondary analysis from the vitamin D and type 2 diabetes (D2d) study. Diabetes Research and Clinical Practice. https://doi.org/10.1016/j.diabres.2023.110792.
DOI: https://doi.org/10.1016/j.diabres.2023.110792

Interpretive Summary: Prediabetes is defined as having a blood sugar level above normal but below the diabetes threshold, and it has been associated with diabetes complications such as early kidney and vascular diseases. Supplementation with vitamin D has been tested as a preventive strategy to reduce risk of progression from prediabetes to type 2 diabetes, but less is known about whether vitamin D might also promote regression from prediabetes to normal glucose regulation. This question was addressed in the D2d study in which 2,434 adults were treated for a median of 2.5 years with either 4000 IU per day of vitamin D or placebo. We found that supplemental vitamin D increased the odds of return to normal glucose by 45%. This finding provides further support for the use of supplemental vitamin D in adults with prediabetes.

Technical Abstract: To examine the effect of vitamin D on regression to normal glucose regulation (NGR) and individual glycemic measures in the vitamin D and type 2 diabetes (D2d) study. RESEARCH DESIGN AND METHODS In as-treated analyses, we examined time to new-onset diabetes; time to new-onset NGR defined as: first occurrence of 2 or 3 glycemic criteria in the normal and none in the diabetes range (NGR-1), and first occurrence of fasting plasma glucose (FPG) and 2 hour glucose after 75g glucose load (2hPG) within the normal range regardless of HbA1c (NGR-2); proportion of participants at the last study visit meeting NGR; change in FPG, 2hPG and HbA1c. RESULTS Among 2434 participants with prediabetes, new-onset diabetes occurred in 9.19 versus 10.98 participants per 100 person-years in vitamin D vs. placebo (hazard ratio [HR] 0.842 [95%CI, 0.712, 0.995]). The HR (95%CI) was 1.16 [0.99, 1.36] for new-onset NGR-1 and 1.06 [0.87, 1.30] for NGR-2. At the last visit, NGR-1 occurred in 12.4% vs. 9.5% in the vitamin D vs. placebo group (rate ratio for vitamin D 1.31 [1.02, 1.70]); NGR-2 occurred in 8.7% vs. 6.0% in the vitamin D vs. placebo group (1.45 [1.05, 2.00]). Mean FPG difference from baseline in the vitamin D versus placebo group was -0.80 mg/dL (95%CI, -1.26, -0.33); changes in 2hPG and HbA1c were not significant. CONCLUSIONS In secondary analyses of D2d focused on efficacy, vitamin D lowered risk of type 2 diabetes and increased likelihood of regression to NGR at the end of the study.