Featured News

Is higher-dose vitamin D a ‘promising approach’ to prevent type 2 diabetes?

Healio featured Dr. Carlos Bernal-Mizrachi’s perspective on a recent study about daily supplementation of vitamin D as a promising approach to prevent type 2 diabetes.

In the Healio article, it stated that 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, MD, MS, professor of medicine at Tufts University School of Medicine and Tufts Medical Center in Boston, told Healio “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. Intermittent, high doses of vitamin D supplementation may not achieve the same protection.”

Carlos Bernal-Mizrachi, MD

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.

In response, Dr. Bernal Mizrachi stated, “Data from multiple observational studies indicate consistent associations between lower 25-(OH)D level concentration and increased diabetes risk. However, the evidence to support general supplementation for the prevention of type 2 diabetes is controversial, mainly because there are significant limitations to the data used to make such recommendations.

The results of the original D2d trial showed no significant differences between the vitamin D and placebo groups in the development of diabetes. Still, there was a trend toward mild risk reduction with vitamin D intervention compared with placebo, suggesting the potential benefit of vitamin D supplementation in this population.

In this new analysis, the authors recognized the post-randomization biases from the D2d trial, including participants who initiated diabetes or weight-loss medication, stopped the trial pills, or took out-of-trial vitamin D from supplements above the trial limit of 1000 IU per day. Therefore, they focused this secondary analysis on determining whether high serum 25-(OH)D level levels measured during the D2d trial prevented the onset of type 2 diabetes.

This study used the cumulative average measure of serum 25-(OH)D level during the trial — intratrial vitamin D — before the primary endpoint’s occurrence as the predictor variable. Participants were stratified based on their 25-(OH)D levels. The HRs for diabetes were estimated by comparing the participants in each intratrial mean 25-(OH)D category to the lowest category of vitamin D sufficiency, equivalent to 20 ng/mL to 30 ng/mL. The results indicate that participants in the vitamin D supplementation treatment group who achieved serum 25-(OH)D levels of 40 ng/mL to 49 ng/mL or at least 50 ng/mL had a diabetes risk that was 48% and 29% of that of their counterparts who only achieved serum vitamin D levels within the normal range. Interestingly, this effect was not significant among individuals in the placebo group who achieved mean intratrial 25-(OH)D levels of at least 40 ng/mL despite a tendency toward diabetes risk reduction. Less than 12% of participants in the placebo group achieved high intratrial levels of at least 40 ng/mL, and there was wide mean intratrial 25-(OH)D coefficient of variation in this group, likely due to lack of continuous daily vitamin D supplementation, that may account for the lack of significance within this group.

This study highlights the importance of future intervention studies with a treat-to-target design to sustain higher 25(OH)D levels and assess whether preventive effects on diabetes progression are sustainable. Further confirmation of these results has the potential to alter the approach to prediabetics and prompt vitamin D supplementation to achieve 25(OH)D levels of at least 40 ng/mL to 50 ng/mL to prevent diabetes progression.”


Carlos Bernal-Mizrachi, MD, Philip E. and Carolyn E. Cryer Professor of Medicine, is the Chief of Endocrinology at St. Louis VA Medical System.