medwireNews: High-dose vitamin D supplementation does not significantly reduce the risk for developing type 2 diabetes among people with prediabetes, show D2d trial data presented at the 79th ADA Scientific Sessions in San Francisco, California, USA.
The study, which was simultaneously published in The New England Journal of Medicine, included 2423 adults (age 30 years and older) who met at least two of the ADA criteria for prediabetes: a fasting plasma glucose level of 100–125 mg/dL (5.6–6.9 mmol/L), a plasma glucose level 2 hours after a 75 g oral glucose load of 140–199 mg/dL (7.8–11.0 mmol/L), and a glycated hemoglobin level (HbA1c) of 5.7% to 6.4% (39 to 47 mmol/mol).
Participants were not excluded from the study on the basis of their baseline vitamin D level and were allowed to use vitamin D and calcium supplements at doses of up to 1000 IU/day and 600 mg/day, respectively, but were excluded if they were currently using diabetes or weight-loss medications.
At baseline, the mean serum 25-hydroxyvitamin D level was 28.0 ng/mL overall and did not differ between individuals randomly assigned to receive vitamin D3 4000 IU/day (n=1211) and those assigned to placebo (n=1212). Mean BMI was 32.1 kg/m2 and mean HbA1c level was 5.9% (48 mmol/mol).
After 24 months of treatment, the mean vitamin D3 level was 54.3 ng/mL in the vitamin D group and 28.8 ng/mL in the placebo group.
During a mean follow-up period of 2.5 years, 293 people in the vitamin D group and 323 in the placebo group developed type 2 diabetes. This gave incidence rates of 9.39 and 10.66 events per 100 person–years, respectively, and a hazard ratio (HR) of 0.88, which was not statistically significant.
However, a borderline significant effect was observed when participants were censored if they started a diabetes or weight-loss medication, discontinued the trial vitamin D tablets, or took out-of-trial vitamin D from supplements above the trial limit, all of which were actively discouraged by the investigators throughout the study to avoid potential confounding.
In this exploratory analysis, type 2 diabetes developed in 22.0% of the vitamin D group and 25.1% of the placebo group, giving a HR of 0.84.
Anastassios Pittas (Tufts Medical Center, Boston, Massachusetts, USA) and co-investigators note that 78.4% of participants had baseline vitamin D levels that were “sufficient according to current recommendations (≥20 ng per milliliter),” and this “may have limited the ability of the trial to detect a significant effect.”
Indeed, when the team restricted the analysis to people with a vitamin D level below 12 ng/mL at baseline, they found that vitamin D supplementation reduced the risk for progression to type 2 diabetes by a significant 62% versus placebo.
But Pittas urged caution when interpreting this finding due to the small numbers (60 taking vitamin D, 20 taking placebo) and the fact that the data were not adjusted for multiple comparisons.
The researchers also report that, relative to placebo, vitamin D3 supplementation did not result in a significantly higher rate of adverse events of special interest including hypercalcemia, low estimated glomerular filtration rate, and kidney stones.
Writing in an accompanying editorial, Deborah Wexler (Harvard Medical School, Boston, Massachusetts, USA) says that “the D2d trial was a well-conducted randomized, controlled trial that addresses an important hypothesis in diabetes prevention.
She continues: “Any benefit of vitamin D for diabetes prevention, if present, is modest and clearly does not pertain to a vitamin D–sufficient population.”
Wexler concludes: “Whether targeting populations with vitamin D levels below 12 ng per milliliter, many of whom have additional risk factors for diabetes, would have an effect on beta-cell function and progression to type 2 diabetes remains unresolved.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
N Engl J Med 2019; doi:10.1056/NEJMoa1900906
N Engl J Med 2019; doi:10.1056/NEJMe1906815