Practice Update: Diabetes

CONFERENCE COVERAGE 12

Autoantigen GADVaccine is Safe for Children at High Risk of Type 1 Diabetes Treatment with autoantigen-specific therapies such as alum-formulated glutamic acid decarboxylase is safe in children at increased risk of developing type 1 diabetes, yet the vaccine does not prevent the development of the disease. This conclusion, based on results of a randomized, double-blind, investigator-initiated trial, was presented at the American Diabetes Association’s 77th Scientific Sessions, from June 9–13. H elena Elding Larsson, MD, PhD, of Lund University, Sweden, explained that glutamate decarboxylase, or participants receiving placebo vs alum-for- mulated glutamic acid decarboxylase.

every 3 months for 5 years, with the oral glucose tolerance test repeated every 6 months and the intravenous glucose tol- erance test repeated at each annual visit during the study. Oral glucose tolerance tests were also performed annually, and intravenous and oral glucose tolerance tests were alternated every 6 months. Results indicated that it is safe to administer alum-formulated glutamic acid decarbox- ylase to children at high risk of type 1 diabetes. No significant preventive effect was observed, however, in the small study sample. The group was composed of children with both normal and impaired glucose toler- ance on enrollment. These subjects were known to progress to type 1 diabetes at different rates, so it was not possible to perform specific subgroup analyses. No difference in adverse events or serious adverse events were observed between

Dr Larsson concluded, “Since our study showed that alum-formulated glutamic acid decarboxylase treatment is safe, we want to explore this treatment further, either in different doses or in combination with other drugs, in prevention studies that may impact patient care. For example, an option is to use repeated, increasingly small doses, as is common in classic immune tolerance treatment for allergic symptoms.” She added, “We collected a large number of immunological samples from the study that have yet to be analyzed to under- stand the possible mechanistic effects of alum-formulated glutamic acid decarbox- ylase. These results will be important to consider in developing new studies with combination therapies.” www.practiceupdate.com/c/54557

glutamic acid decarboxylase, is an enzyme targeted by autoantibodies in individuals who go on to develop type 1 diabetes. Research has reported that injections of glutamic acid decarboxylase may preserve some insulin production for 30 months in those with type 1 diabetes, yet this insulin preservation had not been confirmed in larger-scale studies. Dr Larsson and colleagues set out to eval- uate the effect of alum-formulated glutamic acid decarboxylase on progression to type 1 diabetes in children with ongoing persis- tent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies. Diabetes Prevention-Immune Tolerance (DIAPREV-IT) was the first prevention study where alum-formulated glutamic acid decarboxylase was given before the onset of type 1 diabetes. Its goal was to determine whether alum-formulated glu- tamic acid decarboxylase is safe in children at high risk of developing type 1 diabetes, as an attempt to induce immune tolerance earlier during the autoimmune process, preventing or delaying the process lead- ing to clinical type 1 diabetes. Known risk factors for type 1 diabetes include family history, genetics, geogra- phy and age, with the highest incidence of onset occurring in children 4 to 7 and 10 to 14 years of age. The study was conducted from 2009 to 2017. The trial enrolled 50 children age 4-18 years, without type 1 diabetes, and who harboured positive glutamic acid decarbox- ylase antibodies and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/QAb, or IAA). The children were randomized to either two injections of the previously tested dose of 20 μg alum-formulated glutamic acid decarboxylase administered as a prime- and-boost at days 1 and 30 (no serious adverse reactions have been observed with this regimen) or two injections of placebo. Both intravenous and oral glucose toler- ance tests were performed before the first injection. Follow-up visits were conducted

PracticeUpdate Editorial team.

© ADA/Rodney White 2017

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