C-Peptide Response and HLA Genotypes in Subjects With Recent-Onset Type 1 Diabetes After Immunotherapy With DiaPep277: An Exploratory Study

✍ Scribed by Buzzetti, R.; Cernea, S.; Petrone, A.; Capizzi, M.; Spoletini, M.; Zampetti, S.; Guglielmi, C.; Venditti, C.; Pozzilli, P.

• Book ID: 111873209
• Publisher: American Diabetes Association
• Year: 2011
• Tongue: English
• Weight: 634 KB
• Volume: 60
• Category: Article
• ISSN: 0012-1797
• DOI: 10.2337/db10-0560

✦ Synopsis

OBJECTIVE

To investigate whether lower risk HLA class II genotypes would influence the efficacy of DiaPep277 therapy in protecting β-cell function evaluated by C-peptide secretion in recent-onset type 1 diabetic subjects.

RESEARCH DESIGN AND METHODS

Data were collected from type 1 diabetic subjects enrolled in multicenter phase II studies with a randomized, double-blind, and placebo-controlled design in whom fasting and stimulated C-peptide levels were measured. HLA genotypes were classified in high, moderate, and low risk categories.

RESULTS

A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults. At baseline, there was a significant increase in fasting, maximal, and area under the curve (AUC) C-peptide from high to moderate and low risk HLA genotypes in adults (P for trend <0.04) but not in children. Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype. DiaPep277-treated adults with low risk genotype had significantly higher maximal and AUC C-peptide versus placebo at 12 months (0.04 ± 0.07 vs. −0.28 ± 0.09 nmol/L, P < 0.01, and 0.53 ± 1.3 vs. −4.59 ± 1.5 nmol/L, P < 0.05, respectively). In the moderate risk genotype group, Δmaximal and AUC C-peptide values were significantly higher in DiaPep277-treated versus placebo-treated patients (P < 0.01 and P < 0.05, respectively).

CONCLUSIONS

This exploratory study demonstrates that type 1 diabetic adults with low and moderate risk HLA genotypes benefit the most from intervention with DiaPep277; the only subgroup with an increase of C-peptide at 12 months after diagnosis was the low risk DiaPep277-treated subgroup.