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

Abstract

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.