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Vitamin D as Prevention for Type 2 Diabetes

Apr 3, 2021
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: A'Kira Shavers,  PharmD Candidate, South College School of Pharmacy

A new analysis of the D2d study suggests higher serum vitamin D levels may be necessary to reduce type 2 diabetes risk. 

According to a new analysis of the Vitamin D and Type 2 Diabetes (D2d) study, a daily supplementation of 100 μg (4,000 units) of vitamin D3, to increase blood levels of vitamin D to higher levels than those considered adequate for bone health, may decrease the risk of type 2 diabetes in adults with prediabetes.  Anastassios G. Pittas, MD, MS, professor of medicine at Tufts University School of Medicine and Tufts Medical Center in Boston, told Healio that patients with prediabetes not only need to optimize their lifestyle to lose and balance their average weights, but to supplement with daily Vitamin D which may also help decrease the risk of developing diabetes. He suggested that intermittent doses of Vitamin D supplementation were not beneficial or showed the same protection amount.   


Earlier findings in the D2d study, presented at the 2019 American Diabetes Association Scientific Sessions and published in The New England Journal of Medicine, established that prediabetic adults who were assigned a daily vitamin D supplement for two and a half years were just as likely to develop type 2 diabetes during the follow-up as the patients assigned placebo, regardless of baseline vitamin D status. The original study consisted of 2,423 participants whose data was analyzed by researchers of the study. The participants were aged thirty or below with a body mass index between 24 kilograms per meter squared and 42 kilograms per meter squared.  Participants also had to meet at least two out of the three glycemic criteria for prediabetes diagnosis, including a fasting plasma glucose level between 100 milligrams per deciliter and 125 milligrams per deciliter, a plasma glucose level between 140 milligrams per deciliter and 199 milligrams per deciliter after a two-hour oral glucose tolerance test, or an HbA1c between 5.7 percent and 6.4 percent (44.8% women; mean age, 60 years old; mean BMI, 32 kilograms per meter squared; 33.3% nonwhite).   

Between October 2013 and February 2017, all researchers randomly assigned the patients to 4,000 International Units daily vitamin D (n=1,211; mean baseline vitamin D level, 27.7 nanograms per millimeter) or a placebo (n=1,212; baseline vitamin D level, 28.2 nanograms per milliliter), despite the serum 25-hydroxyvitamin D levels.   

The new analysis of the D2d study was published in Diabetes Care and was analyzed by Pittas and colleagues. The researchers compared the hazard ratios in participants who had the interatrial 25- (OH)D level of fewer than 50 nanomoles per liter with those who had levels of 75 nanomoles per liter to 99 nanomoles per liter, 100 nanomoles per liter to 124 nanomoles per liter, and at least 125 nanomoles per liter.  A level of less than or equal to 50 nanomoles per liter is considered adequate by the National Academy of Medicine in the entire cohort and the trial assignment. The researchers did observe an interaction of trial assignments with initial-25 (OH)D level when predicting the risk for diabetes (P= 0.018).  The hazard ratio for patients with diabetes for an increase of 25 nanomoles per liter in interatrial 25- (OH)D level was recorded as 0.75 (95% CI, 0.68-0.82) among all the participants assigned to Vitamin D and 0.9 (95% CI, 0.8-1.02) among those assigned to placebo. The Hazard ratio for participants developing type 2 diabetes in the groups who received vitamin D and maintained interatrial 25- (OH)D levels of 100 nanomoles per liter to 124 nanomoles per liter and those who kept at least a 125 nanomole per liter were 0.48 (95% CI, 0.29-0.8) and 0.29 (95% CI, 0.17-0.5), respectively. These values were in comparison to the levels of 50 nanomoles per liter to 74 nanomoles per liter.   

Researchers concluded that the results for participants who took a daily vitamin D supplement to maintain a serum 25- (OH)D level of at least 100 nanomoles per liter are a “promising approach” when trying to reduce the risk of type 2 diabetes in adults diagnosed with prediabetes.  Pittas suggested that since the study was only an observational analysis, the final recommendation must wait until a complete publication of the second-largest trial, DPVD study in Japan, and individual participants’ results are all examined to test the hypothesis.   


Practice Pearls:  

  • A daily dose of Vitamin D, 4,000 IU, is beneficial for prediabetic patients. 
  • The benefit is seen when a 25(OH) D level is seen, at least 40 nanograms per milliliter to 50 nanograms per milliliter.   
  • A BMI of 30 kilograms per meter squared or lower is when a benefit was noticed, not above.   


Anastassios G. Pittas, M.D., et al. Vitamin D Supplementation and Prevention of Type 2 Diabetes. New England Journal of Medicine, August 8, 2019.  

Bess Dawson-Hughes et al. Intratrial Exposure to Vitamin D and New-Onset Diabetes Among Adults With Prediabetes: A Secondary Analysis From the Vitamin D and Type 2 Diabetes (D2d) StudyDiabetes Care 2020 Oct; dc201765. 

Schaffer, Regina. Higher-Dose Vitamin D ‘Promising Approach’ to Prevent Type 2 Diabetes. Healio, October 16, 2020 


A’Kira Shavers, PharmD candidate 2021, South College School of Pharmacy