An improved clinical model to predict stimulated C-peptide in children with recent-onset type 1 diabetes

Pediatr Diabetes. 2019 Mar;20(2):166-171. doi: 10.1111/pedi.12808. Epub 2019 Jan 8.

Abstract

Background: Stimulated C-peptide measurement after a mixed meal tolerance test (MMTT) is the accepted gold standard for assessing residual beta-cell function in type 1 diabetes (T1D); however, this approach is impractical outside of clinical trials.

Objective: To develop an improved estimate of residual beta-cell function in children with T1D using commonly measured clinical variables.

Subjects/methods: A clinical model to predict 90-minute MMTT stimulated C-peptide in children with recent-onset T1D was developed from the combined AbATE, START, and TIDAL placebo subjects (n = 46) 6 months post-recruitment using multiple linear regression. This model was then validated in a clinical cohort (Hvidoere study group, n = 262).

Results: A model of estimated C-peptide at 6 months post-diagnosis, which included age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), and insulin dose predicted 90-minute stimulated C-peptide measurements (adjusted R2 = 0.63, P < 0.0001). The predictive value of insulin dose and HbA1c alone (IDAA1c) for 90-minute stimulated C-peptide was significantly lower (R2 = 0.37, P < 0.0001). The slopes of linear regression lines of the estimated and stimulated 90-minute C-peptide levels obtained at 6 and 12 months post diagnosis in the Hvidoere clinical cohort were R2 = 0.36, P < 0.0001 at 6 months and R2 = 0.37, P < 0.0001 at 12 months.

Conclusions: A clinical model including age, gender, BMI, HbA1c, and insulin dose predicts stimulated C-peptide levels in children with recent-onset T1D. Estimated C-peptide is an improved surrogate to monitor residual beta-cell function outside clinical trial settings.

Keywords: C-peptide; beta cell function; partial remission; type 1 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • C-Peptide / metabolism*
  • Child
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Insulin Secretion / physiology
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Male
  • Models, Biological*
  • Prognosis
  • Remission Induction
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • C-Peptide
  • teplizumab