GAD-Alum Treatment Seems Effective in Slowing ResidualBeta-Cell Function Loss: Significant C-peptide level preservation was found among treated patients.
2009 (English)In: Review of Endocrinology, ISSN 1944-9895 (print); 1944-9909 (online), Vol. 01, 28-32 p.Article in journal (Refereed) Published
Stimulated C-peptide levels have been considered an endpoint for assessing beta-cell function preservation early in type 1 diabetes. These levels correlate with improved glycemic control and fewer microvascular complications.13,14,29 We found no significant effect of GAD-alum treatment on the change in the primary endpoint of fasting C-peptide, but an effect was seen on stimulated C-peptide level. Both fasting and stimulated C-peptide levels declined to a significantly smaller degree in the GAD-alum group than in the placebo group after 30 months. The observed protective effect of treatment on C-peptide secretion was seen only in patients treated <6 months after diagnosis.
In our study, the duration and magnitude of the GAD-alum treatment effect appears similar to that reported for anti-CD3 treatment13,14 but without the related adverse events. Especially over the long term, residual insulin secretion affects key clinical outcomes.3 Possible explanations include improved overall metabolic control, reduced fluctuation in blood glucose levels and perhaps increased exposure to C-peptide.30 Our results indicate that two injections of 20 µg GAD-alum may help preserve residual insulin secretion in patients with recent-onset type 1 diabetes. How GAD-alum treatment may work to alter disease progression in type 1 diabetes is unclear. Therapy was otherwise similar in the two study groups, therefore differences in preserved beta-cell function do not appear to be related to more intense insulin treatment or better metabolic control in the GAD-alum group. Although fasting C-peptide level may be influenced by blood glucose level, we found significant C-peptide level preservation before and after adjustment for blood glucose level.
Treatment with GAD-alum had an effect on slowing the loss of residual beta-cell function up to 30 months after intervention and was associated with GAD-specific immune modulation. This did not, however, change the insulin requirement. Our study provides preliminary proof of concept; large-scale confirmatory studies with GAD-alum are under way in the United States and Europe.
Place, publisher, year, edition, pages
Wayne, PA, United States: Bryn Mawr Communications, LLC , 2009. Vol. 01, 28-32 p.
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:liu:diva-52643OAI: oai:DiVA.org:liu-52643DiVA: diva2:284397