Author/Editor		Buzzetti, Raffaella; Cernea, Simona; Petrone, Antonio; Capizzi, Marco; Spoletini, Marlaluisa; Zampetti, Simona; Guglielmi, Chiara; Venditti, Chiara; Pozzilli, Paolo; Battelino, Tadej
Title		C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study
Type		članek
Source		Diabetes
Vol. and No.		Letnik 60, št. 11
Publication year		2011
Volume		str. 3067-72
Language		eng
Abstract		OBJECTIVE: To investigate whether lower risk HLA class II genotypes would influence the efficacy of DiaPep277 therapy in protecting beta-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, Deltamaximal 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.
Descriptors		GENES, MHC CLASS II DIABETES MELLITUS, INSULIN-DEPENDENT C-PEPTIDE IMMUNOTHERAPY GENOTYPE AUTOANTIGENS RANDOMIZED CONTROLLED TRIALS MULTICENTER STUDIES AGE FACTORS CHAPERONIN 60 DOUBLE-BLIND METHOD HYPOGLYCEMIC AGENTS KINETICS PEPTIDE FRAGMENTS