Vitamin D Could Cut Risk of Progression to Type 2 Diabetes in People with Prediabetes

Ethan Balk, MD, MPH

Vitamin D supplementation could reduce risk of progression to diabetes by 15%, according to an analysis of randomized trials in prediabetes.

An analysis of 3 randomized controlled trials in individuals with prediabetes, results of the study indicate trial participants assigned to vitamin D supplement lowered their 3-year absolute risk of progression to diabetes by 3.3% and increased the likelihood of return to normal glucose regulation by 30%.¹

“This [individual participant data] meta-analysis of 3 randomized, double-blinded, placebo-controlled trials specifically designed for diabetes prevention found that vitamin D in people with prediabetes was beneficial in decreasing risk for diabetes and increasing the likelihood of regression to normal glucose regulation, with no offsetting safety signals,” wrote investigators.¹ “Among participants treated with cholecalciferol, achieving and sustaining higher serum 25-hydroxyvitamin D levels conferred progressively lower risk for diabetes.”

Few substances have been examined as extensively in modern medicine as vitamin D. With a seemingly endless number of studies in various patient populations, the role of vitamin D has been diminished and propped up again and again depending on the study. Recently, analysis of the landmark VITAL study has reinvigorated some of these discussions after concluding potential benefit conferred through vitamin D supplementation in the general population may be dependent on baseline BMI.²

In the current study, a team led by Ethan Balk, MD, MPH, of the Brown University School of Public Health, sought to assess the potential of vitamin D for preventing progression to type 2 diabetes among a patient population considered to be at risk. With this in mind, investigators designed a systematic review and meta-analysis of data from randomized, placebo-controlled trials on the topic published within the PubMed, Embase, and ClinicalTrials.gov from database inception through December 9, 2022. For inclusion in the meta-analysis, trials needed to be designed as randomized, double-blinded, placebo-controlled trials, include only adults with prediabetes, evaluate oral vitamin D in any formulation, have new-onset diabetes as the primary outcome, and have an intervention duration of at least 2 years.¹

The investigators initial search returned more than 3800 citations and 270 records. From these, a set of 3 trials met the eligibility criteria. These trials were the Tromsø study, the vitamin D and type 2 diabetes (D2d) study, and the Diabetes Prevention with active Vitamin D (DPVD) study. From these 3 trials, investigators obtained information related to 4190 participants, with 2097 of these having been assigned to receive vitamin D and 2093 assigned to placebo therapy. The overall population had a mean age at baseline of 61 years, a mean BMI of 30 kg/m2, and a mean 25-hydroxyvitamin D level was 63 nmol/L. Investigators also noted 44% of the population were women, 51% self-identified as White or European, 33% self-identified as Asian, and 15% self-identified as Black.¹

During a median follow-up of 3.0 (Interquartile range [IQR], 2.0-3.2) years, new-onset diabetes was observed among 22.7% of those randomized to vitamin D and 25.0% of those in the placebo group. In an adjusted intention-to-treat analysis, results indicated randomization to vitamin D was associated with a 12% reduction in relative risk of new-onset diabetes (HR, 0.88 [95% CI, 0.77-0.99]). In an analysis adjusted for age, gender, BMI, race, and HbA1c, this apparent reduction in relative risk grew to 15% (HR, 0.85 [95% CI, 0.75-0.96]), which investigators pointed out correlated to a 3-year absolute risk reduction (ARR) of 3.3% (95% CI, 0.6-6.0) and a number needed to treat of 30.¹

Among those assigned to vitamin D who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L compared with 50 to 74 nmol/L during follow-up, use of cholecalciferol reduced risk for diabetes by 76% (HR, 0.24 [CI, 0.16-0.36]) relative to placebo therapy, with a 3-year ARR of 18.1% (CI, 11.7% to 24.6%). Further analysis demonstrated randomized to vitamin D was associated with an increased likelihood of regression to normal glucose regulation (Rate ratio [RR], 1.30 [95% CI, 1.16-1.46]). Safety analyses indicated there was no differences in RR for kidney stones (RR, 1.17 [95% CI, 0.69-1.99]), hypercalcemia (RR, 2.34 [95% CI, 0.83-6.66]), hypercalciuria (RR, 1.65 [95% CI, 0.83-3.28]), death (RR, 0.85 [95% CI, 0.31-2.36]).¹

In an editorial, Malachi McKenna, MD, of the University College Dublin, and Mary A.T. Flynn, PhD, RD, of Ulster University, noted the growing mass of data related to vitamin D supplementation in different patient populations and suggested it may be time to call upon professional societies, institutions, and governments to provide recommendations on use where evidence exists.³

“What is the way forward? Professional societies, which advise physicians about benefits and harms of vitamin D therapy, have a duty of care to understand advice from government agencies. They should promote population health recommendations about vitamin D intake requirements, 25-(OH)D thresholds, and safe limits. There are important differences between supplementation and therapy,” wrote the pair.³

References

1. Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and risk for type 2 diabetes in people with Prediabetes. Annals of Internal Medicine. February 2023. doi:10.7326/m22-3018
2. Campbell P. Benefits of vitamin D supplementation could depend on body mass index, study finds. HCP Live. https://www.hcplive.com/view/benefits-of-vitamin-d-supplementation-could-depend-on-body-mass-index-study-finds. Published January 17, 2023. Accessed February 7, 2023.
3. McKenna MJ, Flynn MAT. Preventing type 2 diabetes with vitamin D: Therapy versus supplementation. Annals of Internal Medicine. February 2023. doi:10.7326/m23-0220