SAN FRANCISCO – Vitamin D supplementation did not significantly reduce the risk of progression from prediabetes to type 2 diabetes, according to the landmark D2d study.
A possible reason why the observed reduction was not statistically significant was that most participants already had acceptable levels of vitamin D. Still, the intervention “did not significantly reduce the risk [of diabetes],” Anastassios G. Pittas, MD, professor of medicine at Tufts Medical Center, Boston, said at the annual scientific sessions of the American Diabetes Association.
Vitamin D supplementation has been a hot topic on a range of medical fronts. As a 2016 report noted, “low vitamin D levels are also associated with hypertension, cancer, and cardiovascular disease. In addition, [diabetes] and chronic kidney disease (CKD) are also related to vitamin D levels. Vitamin D deficiency has been linked to onset and progression of [diabetes],” ().
However, as the report noted, “evidence regarding vitamin D levels and [diabetes] is contradictory, and well-controlled studies are needed.”
For thestudy, which was coordinated out of the division of endocrinology at Tufts Medical Center, Dr. Pittas and associates recruited 2,423 patients who were considered to have prediabetes, with at least 2 of 3 ADA criteria: fasting plasma glucose level of 100-125 mg/dL; plasma glucose level 2 hours after a 75-g oral glucose load of 140-199 mg/dL; and hemoglobin A1c (HbA1c) level of 5.7%-6.4%.
All of the patients were at least 30 years old with the exception of American Indians, Alaska Natives, Native Hawaiians and other Pacific Islanders who were allowed to be aged 25-30 years. About 22% had low vitamin D levels.
The mean age of the patients was 60 years, mean body mass index was 32, 45% were women, and 33% were non-white. The trial was powered to show a reduction of 25% or more in diabetes risk with vitamin D.
The researchers randomly assigned 1,211 patients to take a once-daily capsule of vitamin D3 (cholecalciferol; 4,000 IU per day); 1,212 received a placebo.
Patients in the vitamin D group greatly boosted their mean serum 25-hydroxyvitamin D levels, from 27.7 ng/mL at baseline to 54.3 ng/mL at 24 months. In contrast, those in the placebo group saw little change, going from 28.2 ng/mL at baseline to 28.8 ng/mL at 24 months.
At a median follow-up of 2.5 years, with 99% of the study participants remaining in the trial, 616 patients developed diabetes (293 in the vitamin D group, 323 in the placebo group).
The risk was lower in the vitamin D group although the difference was not statistically significant. An analysis revealed no clear differences in any of the subgroups (race, age, body mass index, latitude-based geographic location, calcium supplement intake, and others).
However, a post hoc analysis of patients with vitamin D deficiency, which is defined by the National Academy of Medicine as having a 25-hydroxyvitamin D level of less than 12 ng/mL, showed that the vitamin D group had a 62% reduction in risk of diabetes, compared with placebo.
“Response to a nutritional intervention depends on nutritional status at baseline. Thus, if vitamin D has an effect on diabetes prevention, then people with lower levels of serum 25-hydroxyvitamin D would be expected to have a larger effect from supplementation than would those with higher baseline levels,” Dr. Pittas said.