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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2015-01-01
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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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institution | Kabale University |
issn | 2314-6745 2314-6753 |
language | English |
publishDate | 2015-01-01 |
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series | Journal of Diabetes Research |
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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