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October 16, 2020
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Higher-dose vitamin D ‘promising approach’ to prevent type 2 diabetes

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Disclosures: The authors report no relevant financial disclosures.
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Daily vitamin D supplementation to achieve blood levels of vitamin D higher than typically recommended for bone health may reduce risk for type 2 diabetes among adults with prediabetes, according to a new analysis of the D2d study.

Anastassios G. Pittas

“Among people with prediabetes, in addition to optimizing lifestyle to lose and maintain normal weight, supplementation with daily vitamin D may help reduce risk of developing diabetes,” Anastassios G. Pittas, MD, MS, professor of medicine at Tufts University School of Medicine and Tufts Medical Center in Boston, told Healio. “Intermittent, high doses of vitamin D supplementation may not achieve the same protection.”

Adults receiving recommended vitamin D levels are at a lower risk for developing type 2 diabetes.

As Healio previously reported, the D2d study showed that adults with prediabetes assigned to daily vitamin D supplementation for 2.5 years were just as likely to develop type 2 diabetes during follow-up as similar patients assigned to placebo, regardless of baseline vitamin D status. The findings were presented at the 2019 American Diabetes Association Scientific Sessions and published in The New England Journal of Medicine.

For the original study, researchers analyzed data from 2,423 participants aged at least 30 years with a BMI between 24 kg/m² and 42 kg/m² who met at least two of three glycemic criteria for prediabetes, including a fasting plasma glucose level between 100 mg/dL and 125 mg/dL, a plasma glucose level between 140 mg/dL and 199 mg/dL after a 2-hour oral glucose tolerance test or an HbA1c between 5.7% and 6.4% (44.8% women; mean age, 60 years; mean BMI, 32 kg/m²; 33.3% nonwhite). Between October 2013 and February 2017, researchers randomly assigned participants to 4,000 IU daily vitamin D (n = 1,211; mean baseline vitamin D level, 27.7 ng/mL) or placebo (n = 1,212; mean baseline vitamin D level, 28.2 ng/mL), regardless of serum 25-hydroxyvitamin D level.

In a new analysis of D2d published in Diabetes Care, Pittas and colleagues analyzed intratrial vitamin D exposure among D2d participants, calculated as the cumulative rolling mean of annual serum 25-(OH)D measurements. Researchers compared HRs for diabetes among participants who had intratrial 25-(OH)D levels of less than 50 nmol/L, 75 nmol/L to 99 nmol/L, 100 nmol/L to 124 nmol/L and at least 125 nmol/L with those with levels of 50 nmol/L to 74 nmol/L, which is the range considered adequate by the National Academy of Medicine in the entire cohort and by trial assignment (vitamin D vs. placebo).

Researchers observed an interaction of trial assignment with intratrial 25-(OH)D level in predicting diabetes risk (P = .018). The HR for diabetes for an increase of 25 nmol/L in intratrial 25-(OH)D level was 0.75 (95% CI, 0.68-0.82) among those assigned to vitamin D and 0.9 (95% CI, 0.8-1.02) among those assigned to placebo.

HRs for developing type 2 diabetes among participants who received vitamin D and maintained intratrial 25-(OH)D levels of 100 nmol/L to 124 nmol/L and at least 125 nmol/L were 0.48 (95% CI, 0.29-0.8) and 0.29 (95% CI, 0.17-0.5), respectively, compared with those who maintained a level of 50 nmol/L to 74 nmol/L.

The researchers noted that daily vitamin D supplementation to maintain a serum 25-(OH)D level of at least 100 nmol/L is a “promising approach” to reducing the risk for type 2 diabetes among adults with prediabetes.

“It is unlikely that another large diabetes prevention trial with vitamin D supplementation will be completed, so we have to learn from what is already available,” Pittas said. “Because this was an observational analysis, a final recommendation on vitamin D and diabetes must await full publication of the second largest trial, the DPVD study in Japan, and results from individual participant data meta-analyses that combine results from the three large trials that were specifically designed and conducted to test the hypothesis that vitamin D supplementation reduces diabetes risk.”

Reference:

For more information:

Anastassios G. Pittas, MD, MS, can be reached at email: apittas@tuftsmedicalcenter.org; Twitter: @PittasMD.