Effect of ingested interferon-alpha on beta-cell function in children with new-onset type 1 diabetes

Diabetes Care. 2009 Jul;32(7):1250-5. doi: 10.2337/dc08-2029.

Abstract

Objective: To evaluate the safety and efficacy of ingested human recombinant interferon-alpha (hrIFN-alpha) for preservation of beta-cell function in young patients with recent-onset type 1 diabetes.

Research design and methods: Subjects aged 3-25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-alpha at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal.

Results: Individuals in the placebo group (n = 30) lost 56 +/- 29% of their C-peptide secretion from 0 to 12 months, expressed as area under the curve (AUC) in response to a mixed meal. In contrast, children treated with hrIFN-alpha lost 29 +/- 54 and 48 +/- 35% (for 5,000 [n = 27] and 30,000 units [n = 31], respectively, P = 0.028, ANOVA adjusted for age, baseline C-peptide AUC, and study site). Bonferroni post hoc analyses for placebo versus 5,000 units and placebo versus 30,000 units demonstrated that the overall trend was determined by the 5,000-unit treatment group. Adverse events occurred at similar rates in all treatment groups.

Conclusions: Ingested hrIFN-alpha was safe at the doses used. Patients in the 5,000-unit hrIFN-alpha treatment group maintained more beta-cell function 1 year after study enrollment than individuals in the placebo group, whereas this effect was not observed in patients who received 30,000 units hrIFN-alpha. Further studies of low-dose ingested hrIFN-alpha in new-onset type 1 diabetes are needed to confirm this effect.

Trial registration: ClinicalTrials.gov NCT00024518.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / drug effects
  • C-Peptide / blood*
  • C-Peptide / metabolism
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Nephropathies / prevention & control
  • Double-Blind Method
  • Eating / physiology
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology*
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Placebos
  • Young Adult

Substances

  • Antibodies, Antinuclear
  • C-Peptide
  • Immunologic Factors
  • Interferon-alpha
  • Placebos

Associated data

  • ClinicalTrials.gov/NCT00024518