title: C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study.
abstract: 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.
  
  
  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.
authors: Department of Medicina Interna e Specialità Mediche, Division of Diabetes, University Sapienza, Rome, Italy. raffaella.buzzetti@uniroma1.it
authors: Raffaella
authors: R
authors: Buzzetti
authors: Simona
authors: S
authors: Cernea
authors: Antonio
authors: A
authors: Petrone
authors: Marco
authors: M
authors: Capizzi
authors: Marialuisa
authors: M
authors: Spoletini
authors: Simona
authors: S
authors: Zampetti
authors: Chiara
authors: C
authors: Guglielmi
authors: Chiara
authors: C
authors: Venditti
authors: Paolo
authors: P
authors: Pozzilli
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002096:C-Peptide / Q000097:blood*; D018834:Chaperonin 60 / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005802:Genes, MHC Class II; D056726:Genetic Association Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D002096:C-Peptide; D018834:Chaperonin 60; C447781:DiaPep 277; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D010446:Peptide Fragments