Vitamin D may reduce risk of progression to diabetes from prediabetes

In adults with prediabetes, high-dose vitamin D was associated with a 12% to 15% reduced risk for diabetes compared with placebo, a systematic review and meta-analysis found, but an editorial cautioned about the uncertain risk of adverse effects.

Vitamin D may help reduce the risk of developing diabetes in adults with prediabetes, a recent systematic review and meta-analysis found.

Researchers looked at individual participant data from three randomized, double-blind clinical trials that tested the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes. The trials tested cholecalciferol, 20,000 IU (500 µg) weekly; cholecalciferol, 4,000 IU (100 µg) daily; or eldecalcitol, 0.75 µg daily, versus matching placebos in 4,190 participants (mean age, 61 years; 44% women) with a mean body mass index (BMI) of 30 kg/m2. The primary outcome was time to event for new-onset diabetes. Both unadjusted and adjusted analyses were conducted in an intention-to-treat population. Results were published Feb. 7 by Annals of Internal Medicine.

Over a median follow-up of 3.0 years, new-onset diabetes occurred in 475 of 2,097 (22.7%) participants in the vitamin D group and 524 of 2,093 (25.0%) in the placebo group (8.42 and 9.50 events per 100 person-years, respectively). In the unadjusted intention-to-treat analysis, the hazard ratio (HR) for diabetes with vitamin D was 0.88 (95% CI, 0.77 to 0.99). After adjustment for baseline age, gender, BMI, race, and HbA1c level, the HR with vitamin D was 0.85 (95% CI, 0.75 to 0.96). The absolute risk reduction with vitamin D versus placebo was 3.3% (95% CI, 0.6% to 6.0%), and the number of patients with prediabetes needed to treat was 30 (compared with 7 with intensive lifestyle modification and 14 with metformin in the Diabetes Prevention Program study).

In a secondary analysis, which censored follow-up when participants stopped taking the trial pills, started using a diabetes or weight loss medication, or took supplemental vitamin D at a dose above 1,000 IU/d outside the trial, the primary outcome occurred in 447 participants in the vitamin D group and 505 in the placebo group (8.26 and 9.61 events per 100 person-years, respectively). The unadjusted HR with vitamin D was 0.85 (95% CI, 0.75 to 0.97), and the adjusted HR was 0.83 (95% CI, 0.73 to 0.94). The researchers determined all three trials to be at low risk of bias, and the frequency of prespecified adverse events of interest (kidney stones, hypercalcemia, and hypercalciuria) was low.

The study authors noted that the 12% to 15% reduced risk for diabetes seen in their analyses was below the 25% diabetes risk reduction that the individual trials were powered to detect. They speculated that the “blood 25-hydroxyvitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125 to 150 nmol/L (50 to 60 ng/ml).” The results are not generalizable to the general healthy population, among other limitations, they added.

An accompanying editorial noted that the tolerable upper level of vitamin D intake is set by all government agencies at 100 µg (4,000 IU), corresponding to a 25-hydroxyvitamin D level above 125 nmol/L (50 ng/ml), and that the adverse effects of vitamin D therapy just above that level are unknown.

“There are important differences between supplementation and therapy. Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal, and possibly nonskeletal, disease,” the editorialists wrote. “Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm.”