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


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.
Rother
Kristina I
KI
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA. kr58q@nih.gov
Brown
Rebecca J
RJ
Morales
Miriam M
MM
Wright
Elizabeth
E
Duan
Zhigang
Z
Campbell
Carol
C
Hardin
Dana S
DS
Popovic
Jadranka
J
McEvoy
Robert C
RC
Harlan
David M
DM
Orlander
Philip R
PR
Brod
Staley A
SA
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000187:drug effects; D002096:C-Peptide / Q000097:blood* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D004311:Double-Blind Method; D004435:Eating / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D055815:Young Adult
D000974:Antibodies, Antinuclear; D002096:C-Peptide; D007155:Immunologic Factors; D016898:Interferon-alpha; D010919:Placebos