Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.

<h4>Background</h4>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...

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Autor principal:	David J Klinke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfbd0a34da9a4147ba228d9099c24652
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spelling	oai:doaj.org-article:cfbd0a34da9a4147ba228d9099c246522021-11-18T07:35:10ZAge-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.1932-620310.1371/journal.pone.0026873https://doaj.org/article/cfbd0a34da9a4147ba228d9099c246522011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22073210/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.David J KlinkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e26873 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David J Klinke Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
description	<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	David J Klinke
author_facet	David J Klinke
author_sort	David J Klinke
title	Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
title_short	Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
title_full	Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
title_fullStr	Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
title_full_unstemmed	Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.
title_sort	age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma c-peptide in humans.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/cfbd0a34da9a4147ba228d9099c24652
work_keys_str_mv	AT davidjklinke agecorrectedbetacellmassfollowingonsetoftype1diabetesmellituscorrelateswithplasmacpeptideinhumans
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Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans.

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