age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma c-peptide in humansage-correctedβ细胞群在1型糖尿病的发病与人类血浆c -肽.pdfVIP

Age-Corrected Beta Cell Mass Following Onset of Type 1 Diabetes Mellitus Correlates with Plasma C-Peptide in Humans David J. Klinke II1,2* 1 Department of Chemical Engineering, West Virginia University, Morgantown, West Virginia, United States of America, 2 Department of Immunology, Microbiology, and Cell Biology, West Virginia University, Morgantown, West Virginia, United States of America 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. Methods and Findings: 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 correla