|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 School Of Medicine|
|BRODSKY, IRWIN - Maine Medical Center Research Institute (MMCRI)|
|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 on regression to normal glucose regulation and individual glycemic measures: A secondary analysis among participants adherent to the trial protocol in the randomized clinical trial vitamin D and type 2 diabetes (D2d) study. Diabetes Research and Clinical Practice. https://doi.org/10.1016/j.diabres.2023.110792.
Interpretive Summary: Although diabetes prevention trials typically focus on delaying progression to diabetes, regression to normal glucose regulation (NGR) is a critical outcome because NGR, when compared with prediabetes, is associated with lower risk of microvascular disease. In this ancillary analysis, we examined the proportion of participants meeting NGR at the last study visit in the large D2d vitamin D supplementation trial. In this trial, 2423 adults with prediabetes were treated for a median of 2.5 years with 4000 IU/d of vitamin D3 or placebo. At the last visit, NGR occurred in 8.7% of participants in the vitamin D group and 6.0% in the placebo group. We conclude that vitamin D supplementation, in addition to its recognized role in reducing risk of progression to type 2 diabetes, also appears to have a role in restoring normal glycemic status 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 D2d study. Methods. In per-protocol 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 range (NGR-1) or fasting plasma glucose (FPG) and 2-hour post-load-glucose (2hPG) in the normal range (NGR-2); proportion meeting NGR at the last study visit; and change in FPG, 2hPG, and HbA1c. Results. Among 2423 participants, hazard ratio [HR] for diabetes was 0.84 [95%CI, 0.71, 0.99]). 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% participants in the vitamin D vs. placebo group (rate ratio for vitamin D 1.31 [1.02, 1.70]); whereas, NGR-2 occurred in 8.7% vs. 6.0% (rate ratio for vitamin D 1.45 [1.05, 2.00]). During follow-up, FPG, HbA1c, and 2hPG increased in both groups. Mean difference in FPG favored vitamin D (-0.80 mg/dL; 95%CI, -1.26, -0.33). Conclusions. In secondary analyses among participants adherent to the trial protocol, vitamin D lowered risk of developing diabetes and increased likelihood of NGR at the end of the study.