Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial

Abstract

Context: The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear.

Objective: This work aimed to determine the effect of adjunctive ergocalciferol on residual β-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR.

Methods: A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ± 2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ± 2.9 years.

Results: The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P = .08), glycated hemoglobin A_1c (HbA_1c) (P = .09), insulin dose-adjusted A_1c (IDAA_1c), or total daily dose of insulin. Temporal trends for rising HbA_1c (P = .04) and IDAA_1c (P = .02) were statistically significantly blunted in the ergocalciferol group.

Conclusion: Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A_1c and IDAA_1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.

Keywords: C-peptide; ergocalciferol; partial clinical remission; pediatrics; type 1 diabetes.

Figure 1.

CONSORT (Consolidated Standards of Reporting Trials) flow diagram.

Figure 2.

A graph of the changes in 25-hyroxyvitamin D concentration in a 12-month randomized controlled trial (RCT) of ergocalciferol in youth with new-onset type 1 diabetes. The graph shows a statistically significantly higher 25-hydroxyvitamin D concentration in the ergocalciferol group compared to the placebo at 6 months (P = .01) and at 9 months (P = .02). All P values were adjusted for multiple comparisons.

Figure 3.

A, Trend analysis of the least square estimates (LSE) of the means for fasting C-peptide showing no statistically significant difference in the changes in fasting C-peptide concentration between the ergocalciferol- and placebo-treated patients with type 1 diabetes during the 12-month trial (P = .72). B, Trend analysis of the LSEs of the means for stimulated C-peptide showing no statistically significant difference in the change in stimulated C-peptide concentration at 90 minutes between the ergocalciferol- and placebo-treated patients with type 1 diabetes during the 12-month trial (P = .31). C, LSEs of the means for glycated hemoglobin A_1c (HbA_1c) showing the change in HbA_1c between the ergocalciferol and placebo groups during the trial. Trend analysis shows an increase in HbA_1c value for the combined groups (P < .0001). There was evidence of a faster rate of increase in HbA_1c in the placebo compared to the vitamin group (P = .044). D, LSEs of the means for insulin dose–adjusted A_1c (IDAA_1c) showing the changes in IDAA_1c between the ergocalciferol and placebo groups during the trial. Trend analysis shows an increase in IDAA_1c value for the combined groups (P < .0001). Though IDAA_1c was statistically significantly lower in the placebo group at 3 months, it subsequently rose sharply when compared to the vitamin group (P = .015), suggesting that individuals in the placebo group had greater residual β-cell function at the beginning of the study but lost this function at a faster rate than individuals in the ergocalciferol group.

Figure 4.

Least square estimates of the means for serum tumor necrosis factor α (TNF-α) concentration showing the changes in TNF-α between the ergocalciferol and placebo groups during the trial. The mean of rates of change in TNF-α was 0.03 per 3 months for the placebo group, and 0.01 per 3 months for the ergocalciferol group. Serum TNF-α concentration was statistically significantly lower in the ergocalciferol group at 12 months.