Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose

Diabetes Care. 2016 Oct;39(10):1664-70. doi: 10.2337/dc16-0360. Epub 2016 Jul 15.


Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • C-Peptide / blood*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy
  • Dose-Response Relationship, Drug
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / pharmacology
  • Insulin / therapeutic use*
  • Insulin-Secreting Cells / drug effects
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Young Adult


  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin