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

An Exploratory Study

  1. on behalf of the Diapep Trialists Group*
  1. 1Endocrinology, Department of Medicina Interna e Specialità Mediche, University Sapienza, Rome, Italy
  2. 2Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy
  3. 3Centre of Diabetes and Metabolic Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary, London, U.K.
  1. Corresponding author: Raffaella Buzzetti, raffaella.buzzetti{at}


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.

  • Received April 21, 2010.
  • Accepted July 7, 2011.

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