No effect of the 1alpha,25-dihydroxyvitamin D3 on beta-cell residual function and insulin requirement in adults with new-onset type 1 diabetes

Abstract

Objective: To determine whether daily intake of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is safe and improves beta-cell function in patients with recently diagnosed type 1 diabetes.

Research design and methods: Safety was assessed in an open study of 25 patients aged 18-39 years with recent-onset type 1 diabetes who received 0.25 microg 1,25(OH)(2)D(3) daily for 9 months. An additional 40 patients were randomly assigned to 0.25 microg 1,25(OH)(2)D(3) or placebo daily for 9 months and followed for a total of 18 months for safety, beta-cell function, insulin requirement, and glycemic control.

Results: Safety assessment showed values in the normal range in nearly all patients, regardless of whether they received 1,25(OH)(2)D(3) or placebo. No differences in AUC C-peptide, peak C-peptide, and fasting C-peptide after a mixed-meal tolerance test between the treatment and placebo groups were observed at 9 and 18 months after study entry, with approximately 40% loss for each parameter over the 18-month period. A1C and daily insulin requirement were similar between treatment and placebo groups throughout the study follow-up period.

Conclusions: Treatment with 1,25(OH)(2)D(3) at a daily dose of 0.25 microg was safe but did not reduce loss of beta-cell function.

Trial registration: ClinicalTrials.gov NCT00960635.

Figure 1

Flow of participants. A: Participation in the open study designed to assess safety of 1,25(OH)₂D₃ (n = 25). B: Random assignment into the phase II, randomized, double-blind, placebo-controlled study to assess efficacy of study drug (n = 22 study drug, n = 18 placebo).

Figure 2

Safety parameters. Plasma calcium concentrations (A) and 24-h urinary calcium excretion values (B) for patients who received study drug (n = 47, ■) and patients who received placebo (n = 18, □) over 18 months of follow-up. Data are means ± SEM. The reference calcium plasma levels (2.1–2.6 mmol/l) and urine secretion (<10 mmol/24 h) are indicated by the dotted line. VitD₃, 1α,25-dihydroxyvitamin D₃.

Figure 3

Efficacy parameters. Fasting (A) and AUC C-peptide after mixed-meal stimulation (B), mean A1C (C), and mean insulin requirement per kilogram body weight (D) in the 1,25(OH)₂D₃ treatment group (■) and the placebo group (□). Data are means ± SEM. VitD₃, 1α,25-dihydroxyvitamin D₃.