The findings, published in the New England Journal of Medicine and presented at the 79th Scientific Sessions of the American Diabetes Association in San Francisco, showed that a daily intake of 4,000 international units (IU) of vitamin D3 had no statistically significant effect on the risk of developing type 2 diabetes.
The D2d, launched in 2013, is the largest study to date to directly examine if daily vitamin D supplementation aid prevention of diabetes. The trial followed more than 2,400 adults at high risk of developing type 2 diabetes for an average of 2.5 years.
"Observational studies have reported an association between low levels of vitamin D and increased risk for type 2 diabetes," commented Dr Myrlene Staten, D2d project officer at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH.
"Additionally, smaller studies found that vitamin D could improve the function of beta cells, which produce insulin. However, whether vitamin D supplementation may help prevent or delay type 2 diabetes was not known,” she noted.
However, the multi-centre, randomised, placebo-controlled D2d trial found that vitamin D3 supplementation did not result in a lower risk of diabetes than placebo – a finding that may be backed up by two other recent trials.
Multiple studies … but all under-powered?
“While our trial was being conducted, two other trials that were designed to test whether vitamin D supplementation lowers the risk of type 2 diabetes among persons at risk showed hazard ratios with vitamin D that were similar to those in our trial,” noted the team.
For example, in the Tromsø Vitamin D and T2DM Trial (Norway), 511 adults with prediabetes were randomly assigned to either 20,000 IU per week (approximately 2900 IU per day) of vitamin D£ or placebo. In this study, the risk of diabetes was numerically lower in the vitamin D group than in the placebo group, but the difference was not significant.
Meanwhile, in the Diabetes Prevention with Active Vitamin D study (Japan), 1256 adults with prediabetes were randomly assigned to an active form of vitamin D analogue (eldecalcitol) or placebo. Again, the risk of diabetes was also lower in the vitamin D group than in the placebo group, but the difference was again not significant, the team noted.
Staten and colleagues said the newly published D2d study was powered to detect a 25% lower risk of diabetes with vitamin D compared to placebo.
“On the basis of the results from all three trials, vitamin D supplementation may decrease diabetes risk among persons at risk for diabetes not selected for vitamin D insufficiency by a smaller effect size (10 to 15%), but none of these trials were powered to test this effect size,” they noted.
The D2d study included adults aged 30 or older and assigned participants randomly to either take 4,000 International Units (IU) of the D3 (cholecalciferol) form of vitamin D or a placebo pill daily.
All study participants had their vitamin D levels measured at the start of the study. At that time, about 80% of participants had vitamin D levels considered sufficient. Participants were screened every three to six months for an average of 2.5 years to determine if diabetes had developed.
The team then compared the number of people in each of the two study groups that had progressed to type 2 diabetes.
At the end of the study, 293 out of 1211 participants (24.2%) in the vitamin D group developed diabetes compared to 323 out of 1212 (26.7%) in the placebo group - a difference that did not reach statistical significance. This represents 9.39 and 10.66 events per 100 person-years, respectively, noted the team – who added.
They concluded that among persons at high risk for type 2 diabetes, and not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo.
Source: New England Journal of Medicine
Published online ahead of print and presented at the 79th Scientific Sessions of the American Diabetes Association, doi: 10.1056/NEJMoa1900906
“Vitamin D Supplementation and Prevention of Type 2 Diabetes”
Authors: Anastassios G. Pittas, et al