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Meta-Analysis
. 2017 Jan;60(1):43-49.
doi: 10.1007/s00125-016-4122-1. Epub 2016 Oct 4.

GAD Vaccine Reduces Insulin Loss in Recently Diagnosed Type 1 Diabetes: Findings From a Bayesian Meta-Analysis

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Free PMC article
Meta-Analysis

GAD Vaccine Reduces Insulin Loss in Recently Diagnosed Type 1 Diabetes: Findings From a Bayesian Meta-Analysis

Craig A Beam et al. Diabetologia. .
Free PMC article

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.

Conflict of interest statement

Duality of interest The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
PPBE from two-dose GAD vaccine. Histograms of the results from Bayes analysis of the effect of two-dose GAD treatment relative to placebo. Histogram bars are centred at 5% units representing a 5% increase (if positive) or decrease (if negative) in C-peptide change in treated individuals compared with placebo. The width of each bar represents a range of biological effect (change) of ±2.5% of the bar centre. The height of each bar corresponds to the probability of that range of effect. The sum of the areas of the bars above zero gives the PPBE: (a) Ludvigsson (2008) [4], 99.8%; (b) Wherrett (2011) [5], 32.1%; (c) Ludvigsson (2012) [6], 96.6%; (d) meta-analysis, 98.0%
Fig. 2
Fig. 2
Median C-peptide loss in individuals in the placebo groups. Median (95% CI) of the C-peptide AUC change at approximately 1 year from baseline. The change is expressed as the percentage loss from baseline. Estimates have been adjusted for age and baseline differences between the three studies. DW2011, Wherrett (2011) [5]; JL2008, Ludvigsson (2008) [4]; JL2012, Ludvigsson (2012) [6]

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