title: GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis.
abstract: GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results.
  
  
  
  In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine).
  
  
  
  We estimate that there is a 98% probability that 20 μg GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients.
  
  
  
  The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Biomedical Sciences, Western Michigan University Homer Stryker M.D. School of Medicine, 1000 Oakland Drive, Kalamazoo, MI, 49008-8071, USA. craig.beam@med.wmich.edu.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Beam
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Biomedical Sciences, Western Michigan University Homer Stryker M.D. School of Medicine, 1000 Oakland Drive, Kalamazoo, MI, 49008-8071, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: MacCallum
authors.affiliation: Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.affiliation: Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
authors.forename: Diane K
authors.initials: DK
authors.lastname: Wherrett
authors.affiliation: University of Washington and VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Divison of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
mesh_terms: D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014612:Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D007328:Insulin; D014612:Vaccines; D005968:Glutamate Decarboxylase
keywords: Bayes methods; Glutamic acid decarboxylase (GAD); Meta-analysis; Type 1 diabetes; Vaccine