Association between urinary markers of Nucleic Acid Oxidation andMortality in Type 2 Diabetes A population-based cohort study

Abstract

OBJECTIVEdWe 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 ± 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 METHODSdWe used data from the 970 patients who attended the screening for diabetes complications ± 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-29- deoxyguanosine [8-oxodG] [n = 938]) and RNA oxidation (8-oxoGuo [n = 936]) and mortality. RESULTSdDuring a median of 9.8 years of follow-up, 654 patients died. Urinary 8-oxoGuo assessed ± years after the diagnosis was significantly associated with mortality. The multivariateadjusted hazard ratios for all-cause and diabetes-relatedmortality 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 withmortality. 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. CONCLUSIONSdThe 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 ± years after diagnosis are associated with mortality. Copyright © 2013 by the American Diabetes Association.