Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy

Aim. The aim of this study was to assess the changes of markers of DNA damage by glycation and oxidation in patients with type 2 diabetes and the association with diabetic nephropathy. Methodology. DNA oxidation and glycation adducts were analysed in plasma and urine by stable isotopic dilution anal...

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Main Authors: Sahar Waris, Brigitte M. Winklhofer-Roob, Johannes M. Roob, Sebastian Fuchs, Harald Sourij, Naila Rabbani, Paul J. Thornalley
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2015/915486
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author Sahar Waris
Brigitte M. Winklhofer-Roob
Johannes M. Roob
Sebastian Fuchs
Harald Sourij
Naila Rabbani
Paul J. Thornalley
author_facet Sahar Waris
Brigitte M. Winklhofer-Roob
Johannes M. Roob
Sebastian Fuchs
Harald Sourij
Naila Rabbani
Paul J. Thornalley
author_sort Sahar Waris
collection DOAJ
description Aim. The aim of this study was to assess the changes of markers of DNA damage by glycation and oxidation in patients with type 2 diabetes and the association with diabetic nephropathy. Methodology. DNA oxidation and glycation adducts were analysed in plasma and urine by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. DNA markers analysed were as follows: the oxidation adduct 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-OxodG) and glycation adducts of glyoxal and methylglyoxal—imidazopurinones GdG, MGdG, and N2-(1,R/S-carboxyethyl)deoxyguanosine (CEdG). Results. Plasma 8-OxodG and GdG were increased 2-fold and 6-fold, respectively, in patients with type 2 diabetes, with respect to healthy volunteers. Median urinary excretion rates of 8-OxodG, GdG, MGdG, and CEdG were increased 28-fold, 10-fold, 2-fold, and 2-fold, respectively, in patients with type 2 diabetes with respect to healthy controls. In patients with type 2 diabetes, nephropathy was associated with increased plasma 8-OxodG and increased urinary GdG and CEdG. In a multiple logistic regression model for diabetic nephropathy, diabetic nephropathy was linked to systolic blood pressure and urinary CEdG. Conclusion. DNA oxidative and glycation damage-derived nucleoside adducts are increased in plasma and urine of patients with type 2 diabetes and further increased in patients with diabetic nephropathy.
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spelling doaj-art-48763359bd7544799ceef787a60696722025-02-03T06:08:32ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/915486915486Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic NephropathySahar Waris0Brigitte M. Winklhofer-Roob1Johannes M. Roob2Sebastian Fuchs3Harald Sourij4Naila Rabbani5Paul J. Thornalley6Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UKHuman Nutrition & Metabolism Research and Training Center Graz, Institute of Molecular Biosciences, Karl Franzens University, 8010 Graz, AustriaClinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, AustriaHuman Nutrition & Metabolism Research and Training Center Graz, Institute of Molecular Biosciences, Karl Franzens University, 8010 Graz, AustriaClinical Division of Endocrinology and Nuclear Medicine, Department of Internal Medicine, Medical University of Graz, 8036 Graz, AustriaWarwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UKWarwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UKAim. The aim of this study was to assess the changes of markers of DNA damage by glycation and oxidation in patients with type 2 diabetes and the association with diabetic nephropathy. Methodology. DNA oxidation and glycation adducts were analysed in plasma and urine by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. DNA markers analysed were as follows: the oxidation adduct 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-OxodG) and glycation adducts of glyoxal and methylglyoxal—imidazopurinones GdG, MGdG, and N2-(1,R/S-carboxyethyl)deoxyguanosine (CEdG). Results. Plasma 8-OxodG and GdG were increased 2-fold and 6-fold, respectively, in patients with type 2 diabetes, with respect to healthy volunteers. Median urinary excretion rates of 8-OxodG, GdG, MGdG, and CEdG were increased 28-fold, 10-fold, 2-fold, and 2-fold, respectively, in patients with type 2 diabetes with respect to healthy controls. In patients with type 2 diabetes, nephropathy was associated with increased plasma 8-OxodG and increased urinary GdG and CEdG. In a multiple logistic regression model for diabetic nephropathy, diabetic nephropathy was linked to systolic blood pressure and urinary CEdG. Conclusion. DNA oxidative and glycation damage-derived nucleoside adducts are increased in plasma and urine of patients with type 2 diabetes and further increased in patients with diabetic nephropathy.http://dx.doi.org/10.1155/2015/915486
spellingShingle Sahar Waris
Brigitte M. Winklhofer-Roob
Johannes M. Roob
Sebastian Fuchs
Harald Sourij
Naila Rabbani
Paul J. Thornalley
Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy
Journal of Diabetes Research
title Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy
title_full Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy
title_fullStr Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy
title_full_unstemmed Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy
title_short Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy
title_sort increased dna dicarbonyl glycation and oxidation markers in patients with type 2 diabetes and link to diabetic nephropathy
url http://dx.doi.org/10.1155/2015/915486
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