Association Between Urinary Markers of Nucleic Acid Oxidation and Mortality in Type 2 Diabetes A population-based cohort study

作者：Broedbaek Kasper^*; Siersma Volkert; Henriksen Trine; Weimann Allan; Petersen Morten; Andersen Jon T; Jimenez Solem Espen; Hansen Lars J; Henriksen Jan Erik; Bonnema Steen J; Olivarius Niels de Fine; Poulsen Henrik E

来源：Diabetes Care, 2013, 36(3): 669-676.

DOI：10.2337/dc12-0998

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 18-oxodG1 1n = 9381) and RNA oxidation (8-oxoGuo 1n = 9361) 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 multivariateadjusted 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. Diabetes Care 36:669-676, 2013

• 出版日期2013-3