More than 2 in 5 adults in the United States have prediabetes, a condition characterized by higher than normal blood sugar levels and often leads to type 2 diabetes. A new study finds that vitamin D may help slow or prevent its progression, but only in people with certain genetic mutations.
This research today JAMA network openfound that prediabetic adults with specific mutations in the vitamin D receptor gene had a 19% lower risk of developing diabetes if they took high doses of vitamin D daily.
This discovery could one day help shape more personalized medicine and potentially delay or prevent the onset of diabetes for the majority of the 115 million Americans living with prediabetes.
Researchers analyzed data from the D2d study. The D2d study was a large, multicenter clinical trial testing the effects of 4,000 units of vitamin D per day versus a placebo in more than 2,000 U.S. adults with prediabetes to determine whether high daily doses of vitamin D reduce the likelihood that these particularly high-risk people will develop diabetes.
The first trial did not show a significant reduction in diabetes risk for all participants.
However, the D2d results raised important questions. Could vitamin D still benefit some people? Diabetes has many serious complications that develop slowly over many years. If we can delay the length of time an individual lives with diabetes, we can prevent some of those harmful side effects or reduce their severity. ”
Beth Dawson-Hughes, lead author of the study and principal investigator at the Jean Mayer USDA Center for Aging and Human Nutrition Research at Tufts University
Through previous analyses, the D2d research team found that blood levels of 25-hydroxyvitamin D of 40-50 ng/mL or higher were associated with a substantial and gradual reduction in participants’ risk of developing diabetes.
Vitamin D circulating in the blood is converted to its active form in the body before it binds to vitamin D receptors, proteins that help cells respond to the vitamin. Researchers suspected that 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, and it has been suggested that this vitamin may influence insulin release and blood sugar control.
For the new study, Dawson-Hughes and colleagues analyzed the genetic data of 2,098 trial participants who consented to DNA testing, divided into two groups: those who would benefit from vitamin D supplementation and those who would not. They then compared response rates by subgroups of patients categorized according to three common mutations in the vitamin D receptor gene.
This analysis revealed that adults with the AA mutation in the ApaI vitamin D receptor gene (approximately 30% of the study population) did not respond to daily treatment with high doses of vitamin D compared to placebo. In contrast, the analysis found that adults with AC or CC mutations in the vitamin D receptor gene who received the same treatment had a significantly lower risk of developing diabetes compared to adults who took a placebo.
“The results of this study may be an important step toward developing individualized approaches to reduce the risk of developing type 2 diabetes in high-risk adults,” said study lead author Anastasios Pittas, professor of medicine at Tufts University School of Medicine and chief of endocrinology, diabetes, and metabolism at Tufts Medical Center. “One of the reasons vitamin D is attractive as a potential preventive measure is that it is cheap, widely available, and easy for people to take.”
The authors cautioned that the study results do not mean people need to start taking high doses of vitamin D on their own to prevent diabetes. Current guidelines recommend 600 IU per day for people between the ages of 1 and 70 and 800 IU per day for people over 70. Too much vitamin D can be harmful and is associated with an increased risk of falls and fractures in older adults. Further research is needed to better understand who may benefit from increasing the daily dose.
“Our findings suggest that we may eventually be able to identify which prediabetic patients are most likely to benefit from additional vitamin D supplementation,” Dawson-Hughes said. “In principle, this could involve a single, relatively inexpensive genetic test.”
Research reported in this article was supported by the National Institutes of Health under a Cooperative Agreement with the U.S. Department of Agriculture, Agricultural Research Service and Award Number U01DK098245 (D2d Research). Complete information on authors, methodology, limitations, and conflicts of interest is available in the published article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Agriculture or the National Institutes of Health.
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Dawson Hughes, B. Others. (2026). Effects of vitamin D receptor polymorphisms and vitamin D supplementation on diabetes risk in prediabetic adults. JAMA network open. DOI: 10.1001/jamanetworkopen.2026.7332. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2848109
