The Incidence of Type 2 Diabetes in Patients Receiving Vitamin D Supplementation — ADA 2019

The role of 25-hydroxyvitamin D in the progression of type 2 diabetes continues to be explored after a recent study observes diabetes incidence in high risk patients receiving vitamin supplementation.

Patients with prediabetes or at an increased risk for developing type 2 diabetes are encouraged to make lifestyle modifications aimed at improving glycemic homeostasis through macronutrient control and weight loss. Even patients who are successful with their lifestyle modifications and achieve weight loss goals may still possess an elevated risk of type 2 diabetes. A potential risk that may contribute to the progression of diabetes is reduced serum 25-hydroxyvitamin D levels. Previous studies have found significant associations between impaired pancreatic beta-cell activity leading to insulin resistance and low serum vitamin D concentrations. Data from these previous studies suggest that supplementation of vitamin D could possibly decrease the risk of developing type 2 diabetes in these at-risk individuals.

A recent randomized, double blinded, placebo controlled study that was presented at the 79th annual ADA Scientific Sessions conference aimed to determine if vitamin D supplementation actually decreases the risk of developing type 2 diabetes in patients with at least two of the three total criteria for being diagnosed with prediabetes: fasting plasma glucose values of between 100 and 125 mg/dL, plasma glucose values of between 140 and 199 mg/dL two hours after an oral glucose tolerance test, or an HbA1c between 5.7 and 6.4%. Patients enrolled into this study were 30 years or older and had a BMI of between 24 and 42 m2. Patients that had any criteria for being diagnosed with diabetes or were receiving weight-loss medications or medications to control blood sugars, or receiving vitamin D or calcium supplementation above 1000 units or 600 mg, respectively, per day (prior to enrollment) were excluded from this study.

Random 1:1 assignments of eligible study participants were stratified according to BMI (30 or greater and lower than 30), site of trial data, and race (white or nonwhite). Eligible patients were randomly assigned to receive 4000 IU of vitamin D3 daily or placebo daily. During the study period, patients were counseled to avoid weight loss or diabetic medications as well as to limit vitamin D and calcium intake to less than 1000 units and 600 mg, respectively, from all sources, including multivitamins. Patients part of this study were followed up at month 3 and 6, then every 6 months thereafter.

A total of 2423 patients were included in primary analysis. Patient demographics showed 55.2% of the population was male and two thirds of the population were white in race. The average patient was 60 years old with a BMI of 32.1 m2 and HbA1c of 5.9%. There were no significant differences in baseline serum 25-hydroxyvitamin D levels between the two study groups.

The primary outcome observed in this study was a time to event of new onset type 2 diabetes as outlined by the diagnostic ADA criteria. The primary outcome was met in a total of 616 (25.4%) patients: 293 (24.2%) in the vitamin D group and 323 (26.7%) in the placebo group, with an average follow up time of 2.5 years. After stratification, patients in the vitamin D group demonstrated an insignificant hazard ratio of 0.88 (95% CI 0.75 – 1.04); sensitivity analyses showed similar trends in results.

Although there was a generally high adherence to study medication (85.5%), more patients randomized to the vitamin D group stopped the study medication than those randomized to placebo (11.2% vs 8.9%). Also, a greater number of patients randomized to the placebo group reported that they were taking greater than the limit of 1000 daily units of vitamin D, received from an outside source, than those in the vitamin D group (5% vs 2.6%). There were no significant differences in safety profiles between the two study medications.

In conclusion, supplementation of vitamin D does not significantly reduce the risk of developing type 2 diabetes in high risk patients with prediabetes and vitamin D insufficiency versus placebo. Although not statistically significant, hazard ratios leaned favorably towards the vitamin D group. Along with the fact that more patients in the placebo group were receiving above threshold doses of outsourced vitamin D, supplementation of vitamin D in deficient patients may not be an inappropriate recommendation.

Practice Pearls

• Vitamin D supplementation alone does not significantly reduce the risk of developing type 2 diabetes when compared to placebo.
• Large sample sizes and diverse patient demographics allow the possibility of results from this study to be generalized to the public.
• In patients that are vitamin D deficient, supplementation of vitamin D can be used with other methods of reducing type 2 diabetes risk for greater effects.

Pittas AG, Dawson-Hughes B, Sheehan P, et al. Vitamin D supplementation and prevention of type 2 diabetes. NEJM 2019; [Epub ahead of print]. DOI: 10..1056/NEJMoa1900906.

Adam Chalela B.S., PharmD Candidate, USF College of Pharmacy Class of 2020

Reported at the American Diabetes Association 79th Scientific Sessions June, 2019