The rise and fall of insulin secretion in type 1 diabetes mellitus

Diabetologia. 2006 Feb;49(2):261-70. doi: 10.1007/s00125-005-0100-8. Epub 2006 Jan 11.


An understanding of the natural history of beta cell responses is an essential prerequisite for interventional studies designed to prevent or treat type 1 diabetes. Here we review published data on changes in insulin responses in humans with type 1 diabetes. We also describe a new analysis of C-peptide responses in subjects who are at risk of type 1 diabetes and enrolled in the Diabetes Prevention Trial-1 (DPT-1). C-peptide responses to a mixed meal increase during childhood and through adolescence, but show no significant change during adult life; responses are lower in adults who progress to diabetes than in those who do not. The age-related increase in C-peptide responses may account for the higher levels of C-peptide observed in adults with newly diagnosed type 1 diabetes compared with those in children and adolescents. Based on these findings, we propose a revised model of the natural history of the disease, in which an age-related increase in functional beta cell responses before the onset of autoimmune beta cell damage is an important determinant of the clinical features of the disease.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aging*
  • Autoimmunity
  • Body Mass Index
  • C-Peptide / blood
  • Child
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology
  • Prediabetic State


  • C-Peptide
  • Insulin