02842nas a2200229   4500000000100000008004100001100001700042700003200059700001300091700001800104700001700122700001900139700001800158700001600176700001800192700002200210700002200232245015300254490000600407520218500413022001402598       2018                            d1 aMarre Michel1 aADVANCE Collaborative Group1 aLi Qiang1 aWoodward Mark1 aPoulter Neil1 aZoungas Sophia1 aChalmers John1 aCooper Mark1 aThomas Merlin1 aPickering Raelene1 aTikellis Christos00aRelationship Between Plasma 8-OH-Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial.0 v73 a<p>
<b>BACKGROUND: </b>8-Oxo-2'-deoxyguanosine (8-oxo-2'-dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8-oxo-2'-dG and major cardiovascular outcomes in diabetes mellitus is weak.
</p>

<p>
<b>METHODS AND RESULTS: </b>A case-cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5&nbsp;years of follow-up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8-oxo-2'-dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1-SD increase in plasma 8-oxo-2'-dG was 1.10 (95% confidence interval, 1.01-1.20; =0.03). This was driven by an independent association between plasma 8-oxo-2'-dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10-1.37 [&lt;0.001]). By contrast, no association was seen between 8-oxo-2'-dG and noncardiovascular disease death (of which cancer was the major single cause). 8-Oxo-2'-dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke.
</p>

<p>
<b>CONCLUSIONS: </b>In adults with type 2 diabetes mellitus, increased levels of 8-oxo-2'-dG are independently associated with all-cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus.
</p>

<p>
<b>CLINICAL TRIAL REGISTRATION: </b>URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.
</p>
  a2047-9980