Age-dependent decline of β-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study

Diabetes Obes Metab. 2014 Mar;16(3):262-7. doi: 10.1111/dom.12216. Epub 2013 Oct 29.

Abstract

Aims: C-peptide secretion is currently the only available clinical biomarker to measure residual β-cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose.

Methods: We analysed data from 3929 type 1 diabetes patients recruited from seven European centres representing all age groups at disease onset (childhood, adolescence and adulthood). The influence of the age at onset on β-cell function was investigated in a longitudinal analysis at diagnosis and up to 5-years follow-up.

Results: Fasting C-peptide (FCP) data at diagnosis were available in 3668 patients stratified according to age at diagnosis in four groups (<5 years, n = 344; >5 years < 10 years, n = 668; >10 years < 18 years, n = 991; >18 years, n = 1655). FCP levels were positively correlated with age (p < 0.001); the subsequent decline in FCP over time was log-linear with a greater decline rate in younger age groups (p < 0.0001).

Conclusions: This study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of β-cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.

Keywords: clinical trial; type 1 diabetes; β cell.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Age of Onset
  • Aging* / metabolism
  • Biomarkers / blood
  • C-Peptide / blood*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism*
  • Dose-Response Relationship, Drug
  • Europe
  • Fasting
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Insulin Antibodies / blood*
  • Insulin-Secreting Cells / metabolism*
  • Longitudinal Studies
  • Male

Substances

  • Biomarkers
  • C-Peptide
  • Hypoglycemic Agents
  • Insulin
  • Insulin Antibodies