Urinary collagen fragments are significantly altered in diabetes: a link to pathophysiology

Maahs, D.M. et al. (2010) Urinary collagen fragments are significantly altered in diabetes: a link to pathophysiology. PLoS ONE, 5(9), e13051. (doi: 10.1371/journal.pone.0013051)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0013051


Background: The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D). Methodology/Principal Findings: Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92-95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81-94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81-88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed. Conclusions/Significance: These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling.

Item Type:Articles
Additional Information:This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glasgow Author(s) Enlighten ID:Dominiczak, Professor Anna and Delles, Professor Christian and Mischak, Professor Harald
Authors: Maahs, D.M., Siwy, J., Argilés, À., Cerna, M., Delles, C., Dominiczak, A.F., Gayrard, N., Iphöfer, A., Jänsch, L., Jerums, G., Medek, K., Mischak, H., Navis, G.J., Roob, J.M., Rossing, K., Rossing, P., Rychlík, I., Schiffer, E., Schmieder, R.E., Wascher, T.C., Winklhofer-Roob, B.M., Zimmerli, L.U., Zürbig, P., and Snell-Bergeon, J.K.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Published Online:01 January 2010
Copyright Holders:© 2010 Maahs et al
First Published:First published in PLoS ONE 2010 5(9): e13051
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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