title: Association between urinary markers of nucleic acid oxidation and mortality in type 2 diabetes: a population-based cohort study.
abstract: OBJECTIVE
  We recently showed that RNA oxidation, estimated by urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo), independently predicted mortality in a cohort of 1,381 treatment-naive patients with newly diagnosed type 2 diabetes. In the present investigation, we analyzed urine collected 6 years after the diagnosis to assess the association between urinary markers of nucleic acid oxidation and mortality in patients with established and treated diabetes.
  
  
  METHODS
  We used data from the 970 patients who attended the screening for diabetes complications 6 years after the diagnosis. Cox proportional hazards regression was used to examine the relationship between urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG] [n = 938]) and RNA oxidation (8-oxoGuo [n = 936]) and mortality.
  
  
  RESULTS
  During a median of 9.8 years of follow-up, 654 patients died. Urinary 8-oxoGuo assessed 6 years after the diagnosis was significantly associated with mortality. The multivariate-adjusted hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.86 (95% CI 1.34-2.58) and 1.72 (1.11-2.66), respectively. Conversely, 8-oxodG was not associated with mortality. In addition, we found an association between changes in 8-oxoGuo from diagnosis to 6-year follow-up and mortality, with increased risk in patients with an increase and decreased risk in patients with a decrease in 8-oxoGuo.
  
  
  CONCLUSIONS
  The RNA oxidation marker 8-oxoGuo is an independent predictor of mortality in patients with established and treated type 2 diabetes, and changes in 8-oxoGuo during the first 6 years after diagnosis are associated with mortality.
authors.affiliation: Laboratory of Clinical Pharmacology, Rigshospitalet, Copenhagen, Denmark. kasper.broedbaek@rh.regionh.dk
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.forename: Volkert
authors.initials: V
authors.lastname: Siersma
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.forename: Jon T
authors.initials: JT
authors.lastname: Andersen
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Hansen
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Henriksen
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Bonnema
authors.forename: Niels
authors.initials: N
authors.lastname: de Fine Olivarius
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000401:mortality* / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000378:metabolism* / Q000652:urine*; D010084:Oxidation-Reduction
chemical_list: D009696:Nucleic Acids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine