Untangling the Gordian Knot of Vitamin D Supplementation and Type 2 Diabetes Prevention.

Abstract

Approximately one-third of the adult U.S. population has prediabetes, ∼5–10% of whom will progress to diabetes per year (1,2). Intensive lifestyle changes delay progression to diabetes; however, sustaining lifestyle changes long term is challenging and often insufficient to prevent development of diabetes (3). Simple, inexpensive, and sustainable approaches to complement lifestyle changes are therefore needed to lower diabetes risk in people with prediabetes. Over the last decade, vitamin D has emerged as a potential modifier of the pathophysiology of type 2 diabetes and vitamin D supplementation has been hypothesized as a promising intervention to lower diabetes risk (4). Observational studies report consistent associations between higher blood 25-hydroxy vitamin D [25(OH)D] concentration and lower risk of developing type 2 diabetes in diverse cohorts (5). Mechanistic studies provide a strong biological basis for an important role of vitamin D in improving pancreatic β-cell function, but there is less evidence on its effects on insulin resistance (6). Until recently, evidence from trials examining the effect of vitamin D supplementation for diabetes prevention was lacking. In 2019, the U.S.-based Vitamin D and Type 2 Diabetes (D2d) study reported that participants with prediabetes assigned to vitamin D supplementation had a 12% decrease in risk of developing diabetes compared with placebo, but the change was not statistically significant (hazard ratio [HR] 0.88 [95% CI 0.75–1.04) (7). The effect size in D2d was nearly identical to those reported by two similar but smaller trials (Tromso \[Norway], HR 0.90 [95% CI 0.69–1.18], and Diabetes Prevention with active Vitamin D [DPVD\] \[Japan\], HR 0.87 [95% CI 0.68–1.09]) (8,9). Prior meta-analyses did not include these recent trials; thus, the field is ripe for updated meta-analyses. In the current issue of Diabetes Care , two meta-analyses on this topic are published (10,11) . Pramono …