Inside Pediatrics Spring/Summer 2024

ENDOCRINOLOGY

GABA + GAD COMBINATION SHOWS PROMISE FOR TREATING NEW-ONSET TYPE 1 DIABETES C ould an over-the-counter supplement help save insulin production in new-onset type 1 diabetes? That’s the question pediatric

“It took a lot of luck, hope and a dream we were going to cure diabetes with something safe and oral” to get FDA approval for the trial, she said. The study randomized 97 children (average age of 11) within five weeks of their diagnosis to oral GABA with or without a GAD-alum injection. However, the researchers were constrained to low doses of the compounds, given the FDA’s concern about potential side effects. Although the study didn’t meet its primary goal of preserving beta cell insulin production, the GABA/GAD combination significantly reduced glucagon levels, improving blood sugar levels. The study also found lower levels of the inflammatory cytokine expression implicated in the pathogenesis of type 1 diabetes. There were no adverse effects.

endocrinologists Gail J. Mick, M.D., Kenneth McCormick, M.D. (now retired) and colleagues at Children’s of Alabama set out to explore. The answer, according to their recently published article in the journal Nature Communications , is, quite possibly. The study explored the potential of the amino acid gamma-aminobutyric acid (GABA), found in health food stores, and glutamic acid decarboxylase (GAD), an enzyme that acts on glutamate to form GABA, to preserve pancreatic islet function. GABA is an important neurotransmitter in the brain. However, it is also critical to insulin production, with GABA receptors found within the islet beta cells responsible for insulin production. Meanwhile, GAD converts abundant circulating glutamate from dietary protein and intestinal microbiota into GABA. Animal studies showed their potential to stimulate insulin secretion, inhibit glucagon overproduction, dampen inflammation and promote beta cell regeneration. Still, getting a clinical trial approved in a pediatric population took years. “Nobody does first-line studies in children,” Mick said. “For safety reasons, studies are typically conducted in adults, but in type 1 diabetes, adults differ from children. In children, the autoimmune destruction of insulin secretion is faster.

It’s fascinating, just fascinating. GAIL J. MICK, M.D. “ ”

“Not only did we see reduced glucagon, but there were also beneficial immunologic effects,” Mick said. “We’re delighted by that.” The immunology results were recently published in the journal Biomedicines .

The positive outcomes show enough promise that further studies with higher GABA doses are warranted, Mick said, perhaps in combination with other agents, such as GLP-1 receptor agonists, which also have beta-cell regeneration effects. ●

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