New Study Finds Genetic Key to Vitamin D’s Role in Diabetes Prevention

In a large clinical trial, Tufts University researcher Bess Dawson-Hughes and colleagues found that vitamin D supplements reduced the risk of diabetes only in people with certain genetic variants, pointing to a more personalized approach to prevention.

Dawson Hughes and others. found that prediabetic adults with certain variations in the vitamin D receptor gene had a 19% lower risk of developing diabetes when they took a high daily dose of vitamin D.

Dr. Dawson-Hughes and co-authors analyzed data from the D2d study, a multisite, randomized, double-blind, placebo-controlled clinical trial conducted from October 1, 2013 to November 28, 2018.

The initial trial tested the effect of 4,000 units of vitamin D per day versus a placebo in more than 2,000 U.S. adults with prediabetes to see if a high daily dose of vitamin D would reduce the risk of diabetes in these particularly high-risk people.

However, the study did not find a significant reduction in diabetes risk among all participants.

“But the D2d results raised an important question: Could vitamin D still benefit some people? » said Dr Dawson-Hughes.

“Diabetes causes many serious complications that develop slowly over years. »

“If we can delay the time a person lives with diabetes, we can stop or lessen the severity of some of these harmful side effects. »

Through an earlier analysis, the D2d research team found that blood levels of 40 to 50 ng/mL of 25-hydroxyvitamin D or higher were linked to substantial and progressively greater reductions in participants’ risk of developing diabetes.

Vitamin D circulating in the blood is converted to its active form in the body before binding to the vitamin D receptor, a protein that helps cells respond to the vitamin.

Researchers wondered whether genetic differences in this receptor might explain why some people benefit from vitamin D while others do not.

Insulin-producing cells in the pancreas have vitamin D receptors, suggesting that this vitamin may help influence insulin release and blood sugar control.

For their new study, the scientists analyzed genetic data from 2,098 trial participants who had consented to DNA testing in two groups: participants who appeared to benefit from vitamin D supplementation and those who did not.

They then compared response rates by subgroups of patients sorted by three common variations of the vitamin D receptor gene.

This analysis found that adults with the AA variation in the ApaI vitamin D receptor gene – about 30% of the study population – did not respond to daily treatment with a high dose of vitamin D, compared to placebo.

In contrast, the analysis found that the same treatment in adults with AC or CC variations in the vitamin D receptor gene resulted in a significant reduction in the risk of developing diabetes compared to those taking a placebo.

“The findings could represent an important step toward developing a personalized approach to reduce the risk of developing type 2 diabetes in high-risk adults,” said Professor Anastassios Pittas of Tufts University School of Medicine.

“Part of what makes vitamin D attractive as a potential preventive tool is that it is inexpensive, widely available and easy to take. »

The authors caution that these findings do not mean people should start taking high doses of vitamin D on their own to prevent diabetes.

Current guidelines recommend 600 IU per day for people aged 1 to 70 years and 800 IU per day for those over 70 years old.

Taking too much vitamin D can be harmful and has been linked to an increased risk of falls and fractures in older adults.

More research is needed to better understand which people might benefit from a higher daily dose.

“Our results suggest that we may eventually be able to identify patients with prediabetes who are most likely to benefit from additional vitamin D supplementation,” Dr. Dawson-Hughes said.

“In principle, this could involve a single, relatively inexpensive genetic test.”

The results appear in the newspaper Open JAMA Network.

_____

Bess Dawson-Hughes and others. 2026. Vitamin D receptor polymorphisms and the effect of vitamin D supplementation on diabetes risk in adults with prediabetes. JAMA Open Network 9 (4): e267332; doi: 10.1001/jamanetworkopen.2026.7332