Pursuing type 1 diabetes mellitus and related complications through urinary proteomics

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 163; no. 3; pp. 188 - 199
• Main Authors: Caseiro, Armando, Barros, António, Ferreira, Rita, Padrão, Ana, Aroso, Miguel, Quintaneiro, Cláudio, Pereira, Amélia, Marinheiro, Rosário, Vitorino, Rui, Amado, Francisco
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.03.2014
• Subjects: Biomarkers - urine; Diabetes Complications - urine; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - urine; Diabetic Nephropathies - urine; Diabetic Retinopathy - urine; Electrophoresis, Polyacrylamide Gel; Female; Gas Chromatography-Mass Spectrometry; Humans; Internal Medicine; Male; Proteins - chemistry; Proteins - genetics; Proteinuria; Proteomics; Urinalysis; Gel electrophoresis combined to liquid chromatography-tandem mass spectrometry; SDS; Liquid chromatography- matrix assisted laser desorption ionization; Sodium dodecylsulphate; LC-MALDI; Liquid chromatography-tandem mass spectrometry; Identification; TOF; ACN; TFA; Signal/noise; GeLC-MS/MS; SDS-PAGE; LC-MS/MS; S/N; Trifluoroacetic acid; Sodium dodecylsulphate-polyacrylamide gel electrophoresis; Acetonitrile; alpha-Cyano-4-hydroxycinnamic acid; ID; CHCA; Time-of-flight
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2013.09.005

Diabetes mellitus is a chronic metabolic disease with multiple complications, and its successful management requires early diagnosis, to allow timely interventions. Here, we have comprehensively analyzed the proteome changes in urine of type 1 diabetic subjects with and without complications such as retinopathy and nephropathy. gel electrophoresis combined to liquid chromatography-tandem mass spectrometry (GeLC-MS/MS) analysis of midstream urine highlighted the mechanisms involved in disease pathogenesis as, for instance wound healing and blood coagulation in all diabetics or altered ganglioside metabolism in retinopathy, and also some urinary proteins with potential diagnosis value. From these, gelsolin and antithrombin-III appear as promising diagnosis markers for type 1 diabetes mellitus (T1DM), whereas ephrin type-B receptor 4 and vitamin K-dependent protein Z seem to be promising markers for advanced T1DM disease state presenting retinopathy and nephropathy (T1DM-R + N). Data also suggest urinary ganglioside GM2 activator and beta-hexosaminidase subunit beta as potential urinary markers of retinopathy in diabetics. Taken together, the present exploratory urinary proteomic analysis might be seen as an important starting point for studies targeting specific urinary proteins aimed at the implementation of new biomarkers for the early detection of T1DM-related microvascular complications.