Association between urinary markers of nucleic acid oxidation and mortality in type 2 diabetes: a population-based cohort study

Diabetes Care. 2013 Mar;36(3):669-76. doi: 10.2337/dc12-0998. Epub 2012 Nov 12.

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.

Research design and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetes Mellitus, Type 2 / urine*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nucleic Acids / metabolism*
  • Nucleic Acids / urine*
  • Oxidation-Reduction

Substances

  • Nucleic Acids
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine