Study suggests protective effect of ergocalciferol on beta cells in new-onset type 1 diabetes
USA: A secondary analysis of a randomized clinical trial (RCT) published as a research letter in JAMA Network Open has shed light on the effect of ergocalciferol, an inactivated vitamin D analog, on β-cell function in new-onset type 1 diabetes (T1D).
The researchers showed that high-dose ergocalciferol, also known as vitamin D2, may help preserve β-cell function in kids with new-onset T1D and prolong the partial remission phase.
In the study, ergocalciferol significantly reduced the ratio of fasting proinsulin to C-peptide (PI: C) and slowed the decrease in the percent change from baseline in the area under the curve (%∆AUC) of C-peptide among youths with type 1 diabetes.
The results suggest a protective action of ergocalciferol on β cells and possible mechanisms of action to prolong the partial remission (PR) phase of T1D. Ergocalciferol’s ∆ effect size for β-cell protection (15%) is comparable to that of verapamil, imatinib, and other agents (15%-19.4%). Thus, vitamin D may be combined with other treatments (eg, baricitinib and teplizumab) to prolong PR.
About 30% to 50% residual β-cell function may remain at the time of T1D diagnosis, and this may persist for months or years. A prolonged partial remission phase of T1D leads to decreased long-term complications and improved glycemic control. Previous studies have shown a significant decrease with ergocalciferol, in circulating tumor necrosis factor (TNF)-α and temporal trends in both hemoglobin A1c (HbA1c) and insulin dose–adjusted A1c (IDAA1c), a marker of PR, compared with placebo.
Benjamin Udoka Nwosu, Cohen Children’s Medical Center, New Hyde Park, New York, and colleagues report the effect size of high-dose ergocalciferol (50 000 IU/wk for two months, then biweekly for ten months) versus placebo on β-cell function, denoted by the ratio of fasting proinsulin to C-peptide and the percent change from baseline in the area under the curve of C-peptide.
For this purpose, the researchers conducted a post hoc secondary analysis of a double-blind, single-center, placebo-controlled, parallel-group randomized clinical trial of ergocalciferol vs placebo in youths (aged 10-21 years) with newly diagnosed T1D. They obtained written informed consent from adults and parents and assent from youths (aged <18 years). The study followed the CONSORT reporting guideline.
Exclusion and inclusion criteria included fasting C-peptide (>0.1 nmol/L) or stimulated C-peptide (≥0.2 nmol/L) and a positive diabetes-associated autoantibody profile. Participants entered a run-in phase of 1 to 2 months, maintained a treat-to-target insulin regimen, and were randomized to ergocalciferol or placebo. Participants completed mixed-meal tolerance tests to estimate fasting glucose, C-peptide, and proinsulin (normal range, 3.6-22 pmol/L) at 0, 3, 6, 9, and 12 months.
Of 48 youths with type 1 diabetes eligible for the 12-month trial, 36 were randomized to ergocalciferol or placebo. Their mean age was 13.5 years.
Based on the analysis, the researchers reported the following findings:
- Ergocalciferol significantly decreased fasting PI: C vs placebo (mean [SE], −0.0009 versus 0.0011) for the monthly overall difference in trends.
- · The mean decrease in %∆AUC C-peptide was similar for both groups in the first three months (−10.9 versus −8.2) but subsequently decreased more slowly with ergocalciferol vs placebo (−28.4 versus −41.5), with a significant reduction in monthly overall temporal trends (mean [SE], −2.8% vs −4.7 %).
"Although this RCT was limited by its single-center setting, the results suggest a protective action of ergocalciferol on β cells and possible mechanisms of action to prolong PR," the researchers concluded.
Reference:
Nwosu BU, Parajuli S, Sharma RB, Lee AF. Effect of Ergocalciferol on β-Cell Function in New-Onset Type 1 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(3):e241155. doi:10.1001/jamanetworkopen.2024.1155
