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Diabetologia. 2017 Jan;60(1):43-49. Epub 2016 Oct 4.

GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis.

Author information

1
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.
2
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.
3
Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
4
Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
5
University of Washington and VA Puget Sound Health Care System, Seattle, WA, USA.
6
Divison of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Abstract

AIMS/HYPOTHESIS:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS/INTERPRETATION:

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.

KEYWORDS:

Bayes methods; Glutamic acid decarboxylase (GAD); Meta-analysis; Type 1 diabetes; Vaccine

PMID:
27704166
PMCID:
PMC5856235
DOI:
10.1007/s00125-016-4122-1
[Indexed for MEDLINE]
Free PMC Article

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