C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 11; pp. 3067 - 3072
• Main Authors: Buzzetti, Raffaella, Cernea, Simona, Petrone, Antonio, Capizzi, Marco, Spoletini, Marialuisa, Zampetti, Simona, Guglielmi, Chiara, Venditti, Chiara, Pozzilli, Paolo
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.11.2011
• Subjects: Adolescent; Adult; Age Factors; C-Peptide - blood; Chaperonin 60 - therapeutic use; Child; Child, Preschool; Development and progression; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Double-Blind Method; Drug therapy; Fasting; Female; Genes, MHC Class II; Genetic aspects; Genetic Association Studies; Genetics; Genotype; Genotype & phenotype; Genotypes; Health aspects; Histocompatibility antigens; HLA antigens; HLA histocompatibility antigens; Humans; Hypoglycemic Agents - therapeutic use; Immunologic Factors - therapeutic use; Immunotherapy; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Kinetics; Male; Metabolism; Middle Aged; Peptide Fragments - therapeutic use; Peptides; Physiological aspects; Research design; Risk factors; Type 1 diabetes; Young Adult; Italy
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db10-0560

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. 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. 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). 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.