2023 Top Story in Diabetes: Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes
Many epidemiologic studies have indicated an association between low vitamin D levels and the risk for type 2 diabetes (T2D). As vitamin D receptors are expressed in β-cells, muscle, and other tissues that are important in glucose metabolism, there is a strong biological basis underpinning this association. This has led to several small mechanistic studies that indicate that vitamin D replacement in people who are deficient may have beneficial effects on insulin resistance and insulin secretion. However, a robust demonstration that vitamin D replacement decreases progression to T2D has remained elusive. For example, in the NIH D2d study (the largest randomized controlled trial to date, in which 2423 participants with prediabetes were randomized to vitamin D or placebo and followed for a median of 2.5 years), the hazard ratio for incident T2D was 0.88 (95% CI, 0.75–1.04; P = .12) for vitamin D compared with placebo.1
In the present study, Pittas et al conducted a patient-level meta-analysis of three randomized trials which tested cholecalciferol 20,000 IU (500 mcg) weekly, cholecalciferol 4000 IU (100 mcg) daily, or eldecalcitol 0.75 mcg daily, versus matching placebos.2 In this analysis, vitamin D reduced the risk for diabetes by 15% (HR, 0.85; 95% CI, 0.75–0.96). Moreover, there appeared to be a dose–response effect; those who maintained a higher serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) versus 50 to 74 nmol/L (20–29 ng/mL) had a hazard ratio of 0.24 (CI, 0.16–0.36), or a 76% reduction in incident diabetes. Vitamin D also increased the likelihood of regression to normal glucose regulation by 30%. Finally, they found that vitamin D replacement at these levels was safe and well-tolerated. There was no increase in kidney stones, hypercalcemia, or hypercalciuria with vitamin D treatment as compared with placebo.
Why is this study important? Although the effect size in reducing incident T2D is smaller than has been reported with other interventions such as lifestyle/weight loss, metformin, thiazolidinediones, and GLP-1 receptor agonists, this intervention was cheap, very well–tolerated and effective. Patients with prediabetes are increasingly being diagnosed with routine labs (fasting glucose and HbA1c) in clinical practice, and it is estimated that over 80 million people in the US alone have prediabetes. Despite strong clinical trial evidence from the US National Diabetes Prevention Program, community-based diabetes prevention programs have shown only marginal benefits because of low engagement and reduced effectiveness. Thus, even a 15% reduction in the incidence of T2D with vitamin D replacement could be expected to have significant public health implications and be cost-effective. Moreover, vitamin D for the prevention of T2D could be easily implemented in clinical practice. This paper clearly indicates the need for further research in this important area.
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