GABA falls short for type 1 diabetes prevention in children

BARCELONA – Gamma aminobutyric acid (GABA) alone or given in combination with glutamic acid decarboxylase (GAD) had little to no effect on the progression of type 1 diabetes in children, according to early data presented at the annual meeting of the European Association for the Study of Diabetes.

There was no difference between the two active treatment groups and placebo for the primary outcome measure, which was the effect on meal-stimulated C-peptide secretion before and after 1 year of treatment, study investigator Kenneth L. McCormick, MD, reported, nor was there any difference in glycemic control, based on hemoglobin A_1c (HbA_1c) and insulin dose, between the children who received GABA alone (n = 39) or combined with GAD (n = 22), and those who received placebo (n = 30).

“However, the GABA–GAD combination tended to have greater efficacy [than placebo] in terms of the daily insulin dose and the fasting C-peptide–to–glucagon ratio,” said Dr. McCormick, a pediatric endocrinologist at the University of Alabama at Birmingham.

Some beneficial effects on glucagon were seen with the GABA–GAD combination. “At 12 months, fasting glucagon was reduced [P less than .013] in the GABA–GAD group, compared with placebo,” he said. This was a “novel observation,” because stimulated glucagon was also reduced in this cohort. “This could be a potential salutatory metabolic effect in diabetes.”

The data were the first to be reported from the trial, and results of the immunologic analyses should be available by the end of the year and might reveal more positive effects of GABA and GAD, Dr. McCormick suggested. Data from a “proinsulin analysis” will also be available later.

The inspiration for the trial was a study performed in mice showing that GABA exerted a protective and regenerative effect on the islet beta cells and “reversed diabetes” (Proc Natl Acad Sci USA. 2011;108:11692-7). It took almost 4 years from the publication of that study to enroll the first patient for the current study.

“GABA was intriguing ... first of all, it is available in health food stores and in supermarkets in the United States,” said Dr. McCormick. “It has a strong safety profile, it’s tasteless, and can be given orally – what better could you ask for in a trial of children with type 1 diabetes?”

GABA is thought to have multiple effects in the pancreas, from increasing insulin secretion and suppressing glucagon secretion, to altering inflammation and T-cell populations. “That’s what’s so important to emphasize, besides its metabolic effects, this compound also has immunosuppressant action,” Dr. McCormick noted.

 

The study hypothesis was that treatment with oral GABA, or a combination of GABA–GAD, would hinder the progression of new-onset type 1 diabetes. The double-blind trial was designed to run for 1 year (Contemp Clin Trials. 2019;82:93-100) and recruited 97 children with newly diagnosed type 1 diabetes, aged 4-18 years, who were randomized to the three study groups. They were evaluated at baseline and months 1, 5, 8, and 12.

The trial had several limitations, however, which might explain the findings. A key limitation was that the researchers used a low dose of GABA – 1 to 1.5 g/m² a day, given as a twice-daily oral dose, as mandated by the Food and Drug Administration. “For the GABA dose and the response, we are at the threshold. I don’t believe we are overdosing these kids,” Dr. McCormick said, noting that this is the first study done with GABA in humans.

In fact, GABA has a short half-life of around 2.5-5 hours, so the dose may need to be much higher to show an effect and perhaps administered three times a day, he said.

Another limitation was compliance with the twice-daily medication, especially because 35% of the patients were teenagers, and that it was a young population, with about a third of the patients aged younger that 8 years.

GABA and GABA–GAD should still be studied further, Dr. McCormick concluded, but “additional studies with a higher dose of GABA [given] three times a day, and not twice, are warranted.” Such studies also need to have more participants in each group.

The University of Alabama at Birmingham sponsored the study. Collaborators included Diamyd, NOW Foods, Janssen, and the Juvenile Diabetes Research Foundation. Dr. McCormick did not have any disclosures.

SOURCE: McCormick KL et al. EASD 2019, Abstract S05.1.

BARCELONA – Gamma aminobutyric acid (GABA) alone or given in combination with glutamic acid decarboxylase (GAD) had little to no effect on the progression of type 1 diabetes in children, according to early data presented at the annual meeting of the European Association for the Study of Diabetes.

There was no difference between the two active treatment groups and placebo for the primary outcome measure, which was the effect on meal-stimulated C-peptide secretion before and after 1 year of treatment, study investigator Kenneth L. McCormick, MD, reported, nor was there any difference in glycemic control, based on hemoglobin A_1c (HbA_1c) and insulin dose, between the children who received GABA alone (n = 39) or combined with GAD (n = 22), and those who received placebo (n = 30).

“However, the GABA–GAD combination tended to have greater efficacy [than placebo] in terms of the daily insulin dose and the fasting C-peptide–to–glucagon ratio,” said Dr. McCormick, a pediatric endocrinologist at the University of Alabama at Birmingham.

Some beneficial effects on glucagon were seen with the GABA–GAD combination. “At 12 months, fasting glucagon was reduced [P less than .013] in the GABA–GAD group, compared with placebo,” he said. This was a “novel observation,” because stimulated glucagon was also reduced in this cohort. “This could be a potential salutatory metabolic effect in diabetes.”

The data were the first to be reported from the trial, and results of the immunologic analyses should be available by the end of the year and might reveal more positive effects of GABA and GAD, Dr. McCormick suggested. Data from a “proinsulin analysis” will also be available later.

The inspiration for the trial was a study performed in mice showing that GABA exerted a protective and regenerative effect on the islet beta cells and “reversed diabetes” (Proc Natl Acad Sci USA. 2011;108:11692-7). It took almost 4 years from the publication of that study to enroll the first patient for the current study.

“GABA was intriguing ... first of all, it is available in health food stores and in supermarkets in the United States,” said Dr. McCormick. “It has a strong safety profile, it’s tasteless, and can be given orally – what better could you ask for in a trial of children with type 1 diabetes?”

GABA is thought to have multiple effects in the pancreas, from increasing insulin secretion and suppressing glucagon secretion, to altering inflammation and T-cell populations. “That’s what’s so important to emphasize, besides its metabolic effects, this compound also has immunosuppressant action,” Dr. McCormick noted.

 

The study hypothesis was that treatment with oral GABA, or a combination of GABA–GAD, would hinder the progression of new-onset type 1 diabetes. The double-blind trial was designed to run for 1 year (Contemp Clin Trials. 2019;82:93-100) and recruited 97 children with newly diagnosed type 1 diabetes, aged 4-18 years, who were randomized to the three study groups. They were evaluated at baseline and months 1, 5, 8, and 12.

The trial had several limitations, however, which might explain the findings. A key limitation was that the researchers used a low dose of GABA – 1 to 1.5 g/m² a day, given as a twice-daily oral dose, as mandated by the Food and Drug Administration. “For the GABA dose and the response, we are at the threshold. I don’t believe we are overdosing these kids,” Dr. McCormick said, noting that this is the first study done with GABA in humans.

In fact, GABA has a short half-life of around 2.5-5 hours, so the dose may need to be much higher to show an effect and perhaps administered three times a day, he said.

Another limitation was compliance with the twice-daily medication, especially because 35% of the patients were teenagers, and that it was a young population, with about a third of the patients aged younger that 8 years.

GABA and GABA–GAD should still be studied further, Dr. McCormick concluded, but “additional studies with a higher dose of GABA [given] three times a day, and not twice, are warranted.” Such studies also need to have more participants in each group.

The University of Alabama at Birmingham sponsored the study. Collaborators included Diamyd, NOW Foods, Janssen, and the Juvenile Diabetes Research Foundation. Dr. McCormick did not have any disclosures.

SOURCE: McCormick KL et al. EASD 2019, Abstract S05.1.

BARCELONA – Gamma aminobutyric acid (GABA) alone or given in combination with glutamic acid decarboxylase (GAD) had little to no effect on the progression of type 1 diabetes in children, according to early data presented at the annual meeting of the European Association for the Study of Diabetes.

There was no difference between the two active treatment groups and placebo for the primary outcome measure, which was the effect on meal-stimulated C-peptide secretion before and after 1 year of treatment, study investigator Kenneth L. McCormick, MD, reported, nor was there any difference in glycemic control, based on hemoglobin A_1c (HbA_1c) and insulin dose, between the children who received GABA alone (n = 39) or combined with GAD (n = 22), and those who received placebo (n = 30).

“However, the GABA–GAD combination tended to have greater efficacy [than placebo] in terms of the daily insulin dose and the fasting C-peptide–to–glucagon ratio,” said Dr. McCormick, a pediatric endocrinologist at the University of Alabama at Birmingham.

Some beneficial effects on glucagon were seen with the GABA–GAD combination. “At 12 months, fasting glucagon was reduced [P less than .013] in the GABA–GAD group, compared with placebo,” he said. This was a “novel observation,” because stimulated glucagon was also reduced in this cohort. “This could be a potential salutatory metabolic effect in diabetes.”

The data were the first to be reported from the trial, and results of the immunologic analyses should be available by the end of the year and might reveal more positive effects of GABA and GAD, Dr. McCormick suggested. Data from a “proinsulin analysis” will also be available later.

The inspiration for the trial was a study performed in mice showing that GABA exerted a protective and regenerative effect on the islet beta cells and “reversed diabetes” (Proc Natl Acad Sci USA. 2011;108:11692-7). It took almost 4 years from the publication of that study to enroll the first patient for the current study.

“GABA was intriguing ... first of all, it is available in health food stores and in supermarkets in the United States,” said Dr. McCormick. “It has a strong safety profile, it’s tasteless, and can be given orally – what better could you ask for in a trial of children with type 1 diabetes?”

GABA is thought to have multiple effects in the pancreas, from increasing insulin secretion and suppressing glucagon secretion, to altering inflammation and T-cell populations. “That’s what’s so important to emphasize, besides its metabolic effects, this compound also has immunosuppressant action,” Dr. McCormick noted.

 

The study hypothesis was that treatment with oral GABA, or a combination of GABA–GAD, would hinder the progression of new-onset type 1 diabetes. The double-blind trial was designed to run for 1 year (Contemp Clin Trials. 2019;82:93-100) and recruited 97 children with newly diagnosed type 1 diabetes, aged 4-18 years, who were randomized to the three study groups. They were evaluated at baseline and months 1, 5, 8, and 12.

The trial had several limitations, however, which might explain the findings. A key limitation was that the researchers used a low dose of GABA – 1 to 1.5 g/m² a day, given as a twice-daily oral dose, as mandated by the Food and Drug Administration. “For the GABA dose and the response, we are at the threshold. I don’t believe we are overdosing these kids,” Dr. McCormick said, noting that this is the first study done with GABA in humans.

In fact, GABA has a short half-life of around 2.5-5 hours, so the dose may need to be much higher to show an effect and perhaps administered three times a day, he said.

Another limitation was compliance with the twice-daily medication, especially because 35% of the patients were teenagers, and that it was a young population, with about a third of the patients aged younger that 8 years.

GABA and GABA–GAD should still be studied further, Dr. McCormick concluded, but “additional studies with a higher dose of GABA [given] three times a day, and not twice, are warranted.” Such studies also need to have more participants in each group.

The University of Alabama at Birmingham sponsored the study. Collaborators included Diamyd, NOW Foods, Janssen, and the Juvenile Diabetes Research Foundation. Dr. McCormick did not have any disclosures.

SOURCE: McCormick KL et al. EASD 2019, Abstract S05.1.