Practice Update: Diabetes

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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.
Helena Elding Larsson, MD, PhD, of
Lund University, Sweden, explained
that glutamate decarboxylase, or
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
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
participants receiving placebo vs alum-for-
mulated glutamic acid decarboxylase.
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.”
PracticeUpdate Editorial team.
© ADA/Rodney White 2017
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