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- Title
A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes.
- Authors
Martin, Alexandra; Mick, Gail J.; Choat, Heather M.; Lunsford, Alison A.; Tse, Hubert M.; McGwin Jr., Gerald G.; McCormick, Kenneth L.
- Abstract
Gamma aminobutyric acid(GABA) is synthesized by glutamate decarboxylase(GAD) in β-cells. Regarding Type 1 diabetes(T1D), animal/islet-cell studies found that GABA promotes insulin secretion, inhibits α-cell glucagon and dampens immune inflammation, while GAD immunization may also preserve β-cells. We evaluated the safety and efficacy of oral GABA alone, or combination GABA with GAD, on the preservation of residual insulin secretion in recent-onset T1D. Herein we report a single-center, double-blind, one-year, randomized trial in 97 children conducted March 2015 to June 2019(NCT02002130). Using a 2:1 treatment:placebo ratio, interventions included oral GABA twice-daily(n = 41), or oral GABA plus two-doses GAD-alum(n = 25), versus placebo(n = 31). The primary outcome, preservation of fasting/meal-stimulated c-peptide, was not attained. Of the secondary outcomes, the combination GABA/GAD reduced fasting and meal-stimulated serum glucagon, while the safety/tolerability of GABA was confirmed. There were no clinically significant differences in glycemic control or diabetes antibody titers. Given the low GABA dose for this pediatric trial, future investigations using higher-dose or long-acting GABA formulations, either alone or with GAD-alum, could be considered, although GABA alone or in combination with GAD-alum did nor preserve beta-cell function in this trial. Based on preclinical studies, gamma aminobutyric acid (GABA) and immunization for the enzyme that produces GABA glutamate decarboxylase (GAD) could be a potential therapy for type 1 diabetes. Here the authors report that in a placebo-controlled, double blind trial in children with new onset type 1 diabetes oral GABA plus GAD did not preserve beta-cell function measured as fasting/meal-stimulated c-peptide levels.
- Subjects
ISLANDS of Langerhans; GLUTAMATE decarboxylase; TYPE 1 diabetes; GLYCEMIC control; ANTIBODY titer
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35544-3