Vitamin D Supplementation in Patients With Type 2 Diabetes

The Vitamin D for Established Type 2 Diabetes (DDM2) Study

Edith Angellotti; David D'Alessio; Bess Dawson-Hughes; Jason Nelson; Robert M. Cohen; Amalia Gastaldelli; Anastassios G. Pittas

Disclosures

J Endo Soc. 2018;2(4):310-321. 

In This Article

Abstract and Introduction

Abstract

Context Observational data support a role for vitamin D in type 2 diabetes, but evidence from trials is inconclusive.

Objective To evaluate the effect of vitamin D supplementation on β-cell function and hemoglobin A1c (HbA1c) in patients with well-controlled type 2 diabetes.

Design Double-blind, randomized, placebo-controlled clinical trial.

Setting Tufts Medical Center, Boston, MA; VA Medical Center, Cincinnati, OH.

Participants A total of 127 patients (mean age, 60 years) with stable (HbA1c ≤7.5%) diabetes managed with lifestyle only or lifestyle plus metformin.

Intervention Subjects were given 4000 units of vitamin D3 (cholecalciferol) daily or placebo for 48 weeks.

Main Outcome Measure Insulin secretion rate (ISR) was estimated from peripheral plasma C-peptide levels after a 3-hour 75-g oral glucose tolerance test done at baseline and week 24. Changes in HbA1c were assessed at 16, 24, 36, and 48 weeks.

Results Baseline mean plasma 25-hydroxyvitamin D [25(OH)D] concentration was 26.6 ng/mL, mean HbA1c was 6.6%, and 78% of patients were on metformin. At week 24, mean 25(OH)D changed by 20.5 and −1.6 ng/mL in the vitamin D and placebo groups, respectively (P < 0.001). The vitamin D and placebo groups did not differ in change in ISR or HbA1c. Among patients treated with lifestyle only (n = 28), vitamin D supplementation reduced HbA1c compared with placebo (−0.1% vs 0.3%, respectively; P = 0.034) at week 24. This result was not observed at the other time points and could be due to chance.

Conclusion Vitamin D3 at 4000 IU/d did not change ISR or HbA1c in patients with well-controlled type 2 diabetes on metformin not selected for vitamin D deficiency.

Introduction

Although type 2 diabetes–specific pharmacotherapy is well studied and efficacious, it is associated with poor long-term adherence, potential side effects, and high costs. Therefore, identification of alternative therapeutic options that can be applied at the public health level are needed to decrease diabetes-related burdens and costs.

Suboptimal vitamin D status has emerged as a potential contributor to the pathophysiology of type 2 diabetes, with several lines of evidence supporting a role for vitamin D in pancreatic β-cell function and insulin sensitivity.[1,2] Several trials have examined the effect of vitamin D supplementation (with or without calcium) on glycemia and insulin sensitivity in patients with type 2 diabetes; results are summarized in recent meta-analyses.[3–7] George et al.[3] performed a meta-analysis of trials among patients with type 2 diabetes or impaired glucose tolerance and noted a significant reduction of fasting glucose (~6 mg/dL) and improvement in insulin sensitivity in patients given vitamin D supplementation vs placebo. A meta-analysis by Seida et al.[4] reported nonstatistically significant improvements in hemoglobin A1c (HbA1c), fasting glucose, and insulin sensitivity. In 2017, three meta-analyses of trials using vitamin D in patients with type 2 diabetes reported concordant results.[5–7] In the first study, Wu et al.[5] found that vitamin D supplementation reduced HbA1c significantly (24 trials) and reduced fasting glucose nonsignificantly (18 trials). Among patients with baseline 25-hydroxyvitamin D [25(OH)D] <20 ng/mL, reductions in HbA1c and fasting glucose were significant. In the second study, Mirhosseini et al.[6] reported statistically significant reductions in HbA1c, fasting glucose, and insulin resistance (assessed by Homeostatic Model Assessment of Insulin Resistance) after vitamin D supplementation compared with placebo in an analysis of 24 trials. Finally, Krul-Poel et al.[7] reported no statistically significant improvements in HbA1c and fasting glucose favoring vitamin D. Although the summary results from these meta-analyses support a beneficial effect of vitamin D supplementation on glycemia and insulin sensitivity in patients with type 2 diabetes, the available trials were short term and of varied quality, had small sample sizes, and had a varied mode of vitamin D administration; therefore, definitive conclusions cannot be drawn from individual trials and meta-analyses. Only two small, short-term trials (n = 24 patients, 16 weeks;[8] n = 37 patients, 12 weeks[9] have been conducted in the United States; therefore, the effect of vitamin D supplementation among American adults with type 2 diabetes is not known.

The aim of this study was to evaluate the effectiveness of oral daily vitamin D supplementation on pancreatic β-cell function and glycemia and its safety in US adults with well-controlled type 2 diabetes.

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