Vitamin D may help prevent type 2 diabetes in people with specific genetic variations, offering a possible path toward personalized diabetes prevention.
More than 40% of U.S. adults have prediabetes, a condition in which blood sugar levels are elevated but not yet high enough for a type 2 diabetes diagnosis. New research suggests vitamin D could help slow or prevent that progression in some people, depending on their genetics.
The study, published in JAMA Network Open, found that adults with prediabetes who carried certain variations of the vitamin D receptor gene had a 19% lower risk of developing diabetes when they took a high daily dose of vitamin D.
Researchers say the findings could eventually support more personalized approaches to diabetes prevention for the roughly 115 million Americans living with prediabetes.
The team examined data from the D2d study, a large multi-site clinical trial involving more than 2,000 U.S. adults with prediabetes. Participants received either 4,000 IU of vitamin D daily or a placebo to test whether supplementation could reduce diabetes risk.
Why the Original D2d Trial Raised New Questions
The original D2d trial did not show a significant drop in diabetes risk across all participants.
"But the D2d results raised an important question: Could vitamin D still benefit some people?" said Bess Dawson-Hughes, the study's lead author and a senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University.
"Diabetes has so many serious complications that develop slowly over years. If we can delay the time period that an individual will spend living with diabetes, we can stop some of those harmful side effects or lessen their severity."
Earlier work from the D2d team found that participants with blood levels of 25-hydroxyvitamin D between 40 and 50 ng/mL or higher showed progressively greater reductions in diabetes risk.
Vitamin D Receptor Gene Variations Explained
Vitamin D in the bloodstream must first be converted into its active form before attaching to the vitamin D receptor, a protein that helps cells respond to the nutrient. Researchers suspected that genetic differences in this receptor could explain why vitamin D appeared to help some people but not others. Insulin-producing cells in the pancreas also contain vitamin D receptors, suggesting the vitamin may play a role in insulin release and blood sugar regulation.
For the new analysis, researchers examined genetic data from 2,098 trial participants who agreed to DNA testing. They compared people who appeared to benefit from vitamin D supplementation with those who did not, focusing on three common variations in the vitamin D receptor gene.
The results showed that adults with the AA variation of the ApaI vitamin D receptor gene, which accounted for about 30% of participants, did not benefit from high-dose vitamin D treatment compared with placebo. However, adults with the AC or CC variations experienced a significantly lower risk of developing diabetes when taking vitamin D.
Personalized Diabetes Prevention Potential
"The findings may represent an important step toward developing a personalized approach to lowering the risk of developing type 2 diabetes among high-risk adults," said Anastassios Pittas, the study's senior author, a professor of medicine at Tufts University School of Medicine, and chief of endocrinology, diabetes, and metabolism at Tufts Medical Center.
"Part of what makes vitamin D appealing as a potential preventive tool is that it is inexpensive, widely available, and easy for people to take."
Researchers stressed that the findings should not encourage people to start taking high doses of vitamin D without medical advice. Current recommendations call for 600 IU daily for people ages 1 to 70 and 800 IU daily for adults older than 70.
High Vitamin D Risks and Future Genetic Screening
Too much vitamin D can be harmful and has been associated with a greater risk of falls and fractures in older adults. Scientists say more studies are needed to determine which individuals could safely benefit from higher doses.
"Our findings suggest we may eventually be able to identify which patients with prediabetes are most likely to benefit from additional vitamin D supplementation," said Dawson-Hughes. "In principle, this could involve a single, relatively inexpensive genetic test."
Reference: "Vitamin D Receptor Polymorphisms and the Effect of Vitamin D Supplementation on Diabetes Risk Among Adults With Prediabetes" by Bess Dawson-Hughes, Gordon S. Huggins, Jason Nelson, Ellen Vickery, Sarah N. Powers and Anastassios G. Pittas, 23 April 2026, JAMA Network Open.
DOI: 10.1001/jamanetworkopen.2026.7332
Research reported in this article was supported by a cooperative agreement with the U.S. Department of Agriculture's Agricultural Research Service and by the National Institutes of Health under award number U01DK098245 (D2d study).
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