title: Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose.
abstract: We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function.
  
  
  
  Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixed-meal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained.
  
  
  
  The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individuals with stimulated C-peptide ≥0.2 nmol/L, especially in children.
  
  
  
  Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of disease-modifying therapy on preservation of β-cell function.
authors.affiliation: Diabetes Clinical Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA whao@benaroyaresearch.org.
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, CA.
authors.forename: Steven
authors.initials: S
authors.lastname: Gitelman
authors.affiliation: Department of Pediatrics, Indiana University, Indianapolis, IN.
authors.forename: Linda A
authors.initials: LA
authors.lastname: DiMeglio
authors.affiliation: Department of Pediatrics, University of South Florida, Tampa, FL.
authors.forename: David
authors.initials: D
authors.lastname: Boulware
authors.affiliation: Diabetes Clinical Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D055815:Young Adult
chemical_list: D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin