GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixedmeal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P = 0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.)

Details

Authors
  • Johnny Ludvigsson
  • David Krisky
  • Rosaura Casas
  • Tadej Battelino
  • Luis Castaño
  • James Greening
  • Olga Kordonouri
  • Timo Otonkoski
  • Paolo Pozzilli
  • Jean-Jacques Robert
  • Henk J Veeze
  • Jerry Palmer
  • Co-authors
Organisations
External organisations
  • Linköping University
  • University of the Basque Country
  • Leicester Royal Infirmary
  • University of Helsinki
  • Paris Descartes University
  • University of Washington
  • Diamyd Medical, US
  • University Children's Hospital, Ljubljana
  • Children's Hospital Auf der Bult
  • University Campus Bio-Medico
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)433-442
Number of pages10
JournalNew England Journal of Medicine
Volume366
Issue number5
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes