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

• Published in: Journal of diabetes research 2015-01, Vol.2015 (2015), p.1-10
• Main Authors: Thornalley, Paul J., Sourij, Harald, Fuchs, Sebastian, Roob, Johannes M., Winklhofer-Roob, Brigitte M., Waris, Sahar, Rabbani, Naila
• Format: Article
• Language: English
• Subjects: Age; Aged; Biomarkers; Biomarkers - metabolism; Biopsy; Cholesterol; Chromatography; Creatinine; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Deoxyribonucleic acid; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetic Nephropathies - metabolism; Diabetic nephropathy; Diabetic retinopathy; DNA; DNA damage; DNA Damage - physiology; Female; Glucose; Glycation End Products, Advanced - metabolism; Humans; Male; Metabolism; Metabolites; Middle Aged; Oxidation-Reduction; Plasma; Statistical analysis; Studies; Urine
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2015/915486

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.