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Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes
J J Cook1, I Hudson, L C Harrison
1Department of Endocrinology and Diabetes, Royal Children's Hospital, Victoria, Australia.
Insights
Azathioprine did not improve remission rates in children with new-onset type I diabetes. While showing early effects on insulin secretion, the drug did not significantly alter metabolic control or antibody levels over 12 months.
Area of Science:
- Immunology
- Endocrinology
- Pediatrics
Background:
- Type I diabetes (T1D) is an autoimmune disease characterized by pancreatic beta-cell destruction.
- Preserving residual beta-cell function is crucial for improving T1D management and long-term outcomes.
- Immunosuppressive agents are being investigated to halt or slow the autoimmune process in T1D.
Purpose of the Study:
- To evaluate the efficacy of azathioprine in preserving beta-cell function and achieving remission in newly diagnosed pediatric patients with type I diabetes.
- To assess the impact of azathioprine on metabolic control, autoantibody levels, and clinical outcomes over a 12-month period.
Main Methods:
- A double-blind, placebo-controlled trial involving 49 pediatric patients (aged 2-20 years) with newly diagnosed type I diabetes.
- Patients received either azathioprine (2 mg/kg/day) or a placebo for 12 months, starting within 20 days of diagnosis.
- Outcomes assessed included complete and partial remission, fasting plasma C-peptide levels, C-peptide response to a meal, and autoantibody titers.
Main Results:
- No significant difference in complete or partial remission rates between the azathioprine and placebo groups at 6 or 12 months.
- Fasting plasma C-peptide levels were transiently higher in the azathioprine group at 3 and 6 months, but this difference was not sustained.
- No significant differences were observed in C-peptide response to a meal or in the frequency of islet cell and insulin antibodies between groups.
- Azathioprine was well-tolerated with no significant side effects reported.
Conclusions:
- Azathioprine, at the dosage used, did not significantly influence the remission phase in children with newly diagnosed type I diabetes.
- Despite potential early effects on endogenous insulin secretion, azathioprine monotherapy is not effective in preserving beta-cell function or improving remission rates in this population.
- Further research may explore combination therapies or different immunomodulatory strategies for T1D treatment.
Abstract:
A double-blind controlled trial of azathioprine (2 mg.kg-1.day-1) was conducted with 49 patients aged 2-20 yr (mean 10.8 yr) who had newly diagnosed type I (insulin-dependent) diabetes. Patients were randomly assigned to receive either azathioprine (n = 24) or placebo (n = 25) for 12 mo, beginning within the 20-day period after diagnosis. Baseline clinical and metabolic characteristics did not differ between the two groups. No patient experienced complete remission, defined as restoration of normal carbohydrate tolerance without other treatment. Partial remission, defined as good metabolic control (hemoglobin A1c less than or equal to 7.9%, preprandial blood glucose less than or equal to 8 mM with an insulin dose of less than 0.5 U.kg-1.day-1), occurred in 10 placebo (40%) and 7 azathioprine (29%) patients at 6 mo and in 4 placebo (16%) and 4 azathioprine (17%) patients at 12 mo (differences not significant). Fasting plasma C-peptide was significantly greater in the azathioprine-treated group at 3 and 6 mo, but this difference was not sustained. C-peptide responses to a standard meal and the frequency of islet cell and insulin antibodies did not differ between the two groups over the 12-mo period. Azathioprine caused no significant side effects. We conclude that in the dosage used, and despite early effects on endogenous insulin secretion, azathioprine alone does not influence the remission phase in children with newly diagnosed type I diabetes.