title: Persistent C-peptide: what does it mean?
abstract: OBJECTIVE
  The assumption that patients with an extended duration of type 1 diabetes mellitus (T1D) do not retain residual functional β cells and endogenous insulin production has recently been challenged. The purpose to this review is to highlight some of the key emerging evidence supporting residual insulin and C-peptide secretion in long-standing T1D.
  
  
  RESULTS
  Recent investigations conducted in a group of type 1 diabetics of long-term duration, characterized clinically and histologically, provided solid evidence to suggest that pancreatic β cells are still present even after 50 years in a majority of these individuals. These residual β cells can secrete insulin in a physiologically regulated manner. Several published reports showed promising effects of glucagon-like peptide 1 (GLP-1) agonists on the glycemic control and residual C-peptide production in long-term T1D, although prospective studies are needed to rule out the potential long-term adverse effects of these drugs.
  
  
  CONCLUSIONS
  C-peptide is no longer considered an irrelevant by-product of insulin biosynthesis. In-depth basic and translational investigations aimed at understanding the molecular immunology and the pathophysiology are needed to elucidate the mechanisms underlying the residual insulin and C-peptide production in long-term T1D. This may shed light on to the regenerative capacity of β cells, the genetic susceptibility of the mechanisms of resistance to β-cell destruction, and possibly identifying new therapeutic strategies for T1D. Studies evaluating the long-term effects of insulin secretogogue agents along with immune intervention hold promise for their use in future clinical trials for long-term T1D.
authors.affiliation: Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, The Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA. maxtp@umich.edu
authors.forename: Massimo
authors.initials: M
authors.lastname: Pietropaolo
mesh_terms: D002096:C-Peptide / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism
chemical_list: D002096:C-Peptide; D007328:Insulin; D052216:Glucagon-Like Peptide 1