For patients with type 2 diabetes, increased levels of 8-Oxo-2′-deoxyguanosine (8-oxo-2′-dG) are associated with both all-cause mortality and cardiovascular (CV) mortality, according to results published in the Journal of the American Heart Association. This represents the prospective study confirming an independent relationship between CV mortality and oxidative DNA damage in type 2 diabetes.
A biomarker of oxidative DNA damage, 8-oxo-2′-dG has already been associated with CV disease (CVD) and premature mortality in the general population.
The study included participants with prevalent diabetes mellitus (n=3766) in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ClinicalTrials.gov Identifier: NCT00145925).
The researchers derived hazard ratios for mortality and major acute CV events using Cox regression models.
During a median 5 years of follow-up, 18.4% (n=695) of participants died. Of these, 354 deaths were from CVD. Participants with higher levels of 8-oxo-2′-dG had an increased risk for death.
After adjusting for CVD risk factors, the researchers found that the hazard ratio for a 1-standard deviation increase in plasma 8-oxo-2′-dG was 1.10 (95% CI, 1.01-1.20; P =.03).
They also found that 8-oxo-2′-dG was independently associated with CV death (hazard ratio, 1.23; 95% confidence interval, 1.10-1.37 [P <.001]).
The researchers did not find an association between 8-oxo-2′-dG and non-CVD death, nonfatal myocardial infarction, or nonfatal stroke.
“This observation supports the call for better-targeted antioxidant therapies and well-designed appropriately powered human studies, especially in those with elevated CVD risk, in whom oxidative stress is usually particularly high and remains untreated,” the researchers wrote.
Thomas MC, Woodward M, Li Q, et al. Relationship between plasma 8-OH-deoxyguanosine and cardiovascular disease and survival in type 2 diabetes mellitus: results from the ADVANCE trial [published online June 30, 2018]. J Am Heart Assoc. doi:10.1161/JAHA.117.008226