title: Increased DNA dicarbonyl glycation and oxidation markers in patients with type 2 diabetes and link to diabetic nephropathy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Waris
authors.affiliation: Human Nutrition & Metabolism Research and Training Center Graz, Institute of Molecular Biosciences, Karl Franzens University, 8010 Graz, Austria.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Winklhofer-Roob
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Roob
authors.affiliation: Human Nutrition & Metabolism Research and Training Center Graz, Institute of Molecular Biosciences, Karl Franzens University, 8010 Graz, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Clinical Division of Endocrinology and Nuclear Medicine, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Sourij
authors.affiliation: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UK ; Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Naila
authors.initials: N
authors.lastname: Rabbani
authors.affiliation: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UK ; Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine