title: Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
abstract: BACKGROUND
  The inability to produce insulin endogenously precipitates the clinical symptoms of type 1 diabetes mellitus. However, the dynamic trajectory of beta cell destruction following onset remains unclear. Using model-based inference, the severity of beta cell destruction at onset decreases with age where, on average, a 40% reduction in beta cell mass was sufficient to precipitate clinical symptoms at 20 years of age. While plasma C-peptide provides a surrogate measure of endogenous insulin production post-onset, it is unclear as to whether plasma C-peptide represents changes in beta cell mass or beta cell function. The objective of this paper was to determine the relationship between beta cell mass and endogenous insulin production post-onset.
  
  
  RESULTS
  Model-based inference was used to compare direct measures of beta cell mass in 102 patients against contemporary measures of plasma C-peptide obtained from three studies that collectively followed 834 patients post-onset of clinical symptoms. An empirical Bayesian approach was used to establish the level of confidence associated with the model prediction. Age-corrected estimates of beta cell mass that were inferred from a series of landmark pancreatic autopsy studies significantly correlate (p>0.9995) with contemporary measures of plasma C-peptide levels following onset.
  
  
  CONCLUSIONS
  Given the correlation between beta cell mass and plasma C-peptide following onset, plasma C-peptide may provide a surrogate measure of beta cell mass in humans. The clinical relevance of this study is that therapeutic strategies that provide an increase in plasma C-peptide over the predicted value for an individual may actually improve beta cell mass. The model predictions may establish a standard historical "control" group - a prior in a Bayesian context - for clinical trials.
authors.affiliation: Department of Chemical Engineering, West Virginia University, Morgantown, West Virginia, United States of America. david.klinke@mail.wvu.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Klinke
mesh_terms: D001499:Bayes Theorem; D002096:C-Peptide / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology*; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology*
chemical_list: D002096:C-Peptide
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