Glutamic acid decarboxylase may help to preserve residual insulin secretion

Treatment with alum-formulated glutamic acid decarboxylase contributed to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, but did not change the insulin requirement in a recent study.

The researchers from Linköping University in Sweden and other sites randomly assigned 70 patients with type 1 diabetes to injections of 20 mcg of glutamic acid decarboxylase–alum (n=35) or placebo/alum alone (n=35). Patients had fasting C-peptide levels >0.1 nmol/L and glutamic acid decarboxylase autoantibodies. They were enrolled within 18 months after receiving the diagnosis of diabetes, according to the researchers.

Insulin secretion gradually decreased in both groups, but the treatment had no significant effect on change in fasting C-peptide after 15 months, according to the researchers.

After 30 months, C-peptide levels decreased by –0.21 nmol/L in the glutamic acid decarboxylase-alum group vs. the placebo group (–0.27 nmol/L; P=.045). Stimulated secretion measured as area under the curve was –0.72 nmol/L/two hours in the glutamic acid decarboxylase–alum group compared with the placebo group (–1.02 nmol/L/two hours; P=.04).

“Our results provide preliminary proof of concept; large-scale confirmatory studies with glutamic acid decarboxylase–alum are underway in Europe and the United States,” the researchers wrote. – by Christen Haigh

N Engl J Med. 2008;doi:10.1056/NEJMoa0804328.

The concept of immune therapy of type 1 diabetes has been of great interest for decades, with a great deal of evidence that it is an autoimmune disease, but the dilemma has been the toxicity of immunosuppression. To avoid this, various studies have been conducted to manipulate the immune system in a more beta cell–specific fashion. This represents one in a series of efforts to immunize people with early diabetes or prediabetes with beta-cell antigens to induce regulatory T cells, which will reduce the cytotoxic T-cell response that leads to islet destruction. Almost certainly, single treatments will not be effective, as shown by the study, but the important approaches to be developed will involve combination approaches, perhaps including insulin, glutamic acid decarboxylase, proinsulin, etc as beta-cell antigens to modify the immune process with other treatments such as anti-CD3 antibody.

– Zachary T. Bloomgarden, MD

Endocrine Today Editorial Board member