Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology
Open Access
- 28 September 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (9), e13051
- https://doi.org/10.1371/journal.pone.0013051
Abstract
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). 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. 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.Keywords
This publication has 53 references indexed in Scilit:
- Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney DiseaseMolecular & Cellular Proteomics, 2010
- Haptoglobin Genotype and Renal Function Decline in Type 1 DiabetesDiabetes, 2009
- The human urinary proteome reveals high similarity between kidney aging and chronic kidney diseaseProteomics, 2009
- Evaluation of Urinary Biomarkers for Coronary Artery Disease, Diabetes, and Diabetic Kidney DiseaseDiabetes Technology & Therapeutics, 2009
- Capillary electrophoresis–mass spectrometry as a powerful tool in biomarker discovery and clinical diagnosis: An update of recent developmentsMass Spectrometry Reviews, 2008
- Urinary Proteomics in Diabetes and CKDJournal of the American Society of Nephrology, 2008
- Tubular function in diabetic children assessed by Tamm-Horsfall protein and glutathione S-transferasePediatric Nephrology, 2008
- Discovery and validation of urinary biomarkers for prostate cancerProteomics – Clinical Applications, 2008
- Urinary Proteomic Biomarkers in Coronary Artery DiseaseMolecular & Cellular Proteomics, 2008
- Mass spectrometry for the detection of differentially expressed proteins: a comparison of surface‐enhanced laser desorption/ionization and capillary electrophoresis/mass spectrometryRapid Communications in Mass Spectrometry, 2003