Serum 25(OH)D and diabetes risk in adults with prediabetes: evidence, potential mechanisms, and implications

Correcting vitamin D deficiency to reach 25-hydroxyvitamin D levels in the replete range (≥ 20 ng/mL, as defined by the National Academy of Medicine) improves insulin secretion and sensitivity. Emerging evidence indicates that vitamin D may have a more extensive role in reducing risk of type 2 diabetes in selected adults with prediabetes. Specifically, vitamin D supplementation at doses sufficient to achieve 25-hydroxyvitamin D levels ≥ 40 ng/ml appears to confer additional benefit in reducing diabetes risk in subsets of the population with prediabetes. Herein we review evidence that achieving relatively high 25-hydroxyvitamin D levels may lower risk of progression to type 2 diabetes in selected vitamin D-replete adults with prediabetes. We consider potential mechanisms by which this may occur. We also discuss the potential benefits and risks of high-dose vitamin D supplementation across subgroups defined by genetic profile, age, and the presence of additional comorbidities. These findings indicate a potential role for a precision nutrition approach with high-dose vitamin D supplementation to lower risk of type 2 diabetes in adults with prediabetes.