C-Peptide Levels in Subjects Followed Longitudinally Before and After Type 1 Diabetes Diagnosis in TrialNet

Diabetes Care. 2020 Aug;43(8):1836-1842. doi: 10.2337/dc19-2288. Epub 2020 May 26.


Objective: Insulin secretion declines rapidly after diagnosis of type 1 diabetes, followed by a slower rate of change. Previous studies have demonstrated that the C-peptide decline begins before the clinical diagnosis. Changes in insulin secretion in the same individuals studied from preclinical stages through and after clinical diagnosis have not been previously reported.

Research design and methods: Antibody-positive relatives undergo sequential oral glucose tolerance testing (OGTT) as part of TrialNet's Pathway to Prevention study and continue both OGTT and mixed-meal tolerance testing (MMTT) as part of the Long-term Investigational Follow-up in TrialNet study if they develop type 1 diabetes. We analyzed glucose and C-peptide data obtained from 80 TrialNet subjects who had OGTT before and after clinical diagnosis. Separately, we compared C-peptide response to OGTT and MMTT in 127 participants after diagnosis.

Results: C-peptide did not change significantly until 6 months before the clinical diagnosis of type 1 diabetes and continued to decline postdiagnosis, and the rates of decline for the first 6 months postdiagnosis were similar to the 6 months prediagnosis. There were no significant differences in MMTT and OGTT C-peptide responses in paired tests postdiagnosis.

Conclusions: This is the first analysis of C-peptide levels in longitudinally monitored patients with type 1 diabetes studied from before diagnosis and continuing to the postdiagnosis period. These data highlight the discordant timing between accelerated β-cell dysfunction and the current glucose thresholds for clinical diagnosis. To preserve β-cell function, disease-modifying therapy should start at or before the acute decline in C-peptide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / metabolism
  • C-Peptide / analysis
  • C-Peptide / blood*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / pathology
  • Diagnostic Techniques, Endocrine
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Humans
  • Insulin Secretion / physiology
  • Longitudinal Studies
  • Male
  • Meals
  • Middle Aged
  • Monitoring, Physiologic
  • Young Adult


  • Blood Glucose
  • C-Peptide