Urinary Markers of Nucleic Acid Oxidation and Long-Term Mortality of Newly Diagnosed Type 2 Diabetic Patients

Broedbaek, Kasper; Siersma, Volkert; Henriksen, Trine; Weimann, Allan; Petersen, Morten Aagaard; Andersen, Jón Trærup; Jimenez-Solem, Espen; Stovgaard, Elisabeth Specht; Hansen, Lars; Henriksen, Jan Erik; Bonnema, Steen Joop; Olivarius, Niels de Fine; Poulsen, Henrik E.

doi:10.2337/dc11-1620

Cited by 96 publications

(62 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, we demonstrate that 8‐oxo‐2′‐dG, a marker of oxidative damage, is independently associated with all‐cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial. This finding is consistent with smaller observational studies linking survival of patients with diabetes mellitus to other markers of oxidative stress, including oxidized RNA,10, 11 derivatives of reactive oxygen metabolite,19 advanced autoxidation products,2, 20 and F‐isoprostanes 2, 20. However, this is the first large prospective study to confirm an independent association between mortality and 8‐oxo‐2′‐dG in type 2 diabetes mellitus.…”

Section: Discussionsupporting

confidence: 89%

“…Urinary 8‐oxo‐2′‐dG has been independently associated with cardiovascular disease (CVD) in population cohorts4, 5, 6 and long‐term survival in patients with advanced CKD,7 heart failure (HF),8, 9 or cancer 2, 3. Yet, despite the recognized role of oxidative stress in diabetic complications, previous studies reported that spot urinary levels of 8‐oxo‐2′‐dG at diagnosis were not associated with subsequent mortality in Danish patients with type 2 diabetes mellitus 10, 11. This surprising finding may reflect the challenges of quantitative urinalysis in patients with type 2 diabetes mellitus in the community, especially when patients are poorly controlled (with polyuria and hyperfiltration) or have renal disease.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

View full text Add to dashboard Cite

Background8‐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.Methods and ResultsA 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 (http://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 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; P=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 [P<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.ConclusionsIn 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.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…IsoP and 8-OHdG are among the most commonly reported markers, in part due to their stability in vivo (Akagi et al, 2003; Milne et al, 2007). 8-oxoG is comparatively less common, but increasingly important (Poulsen et al, 2012); for example, urinary 8-oxoG (but not 8-OHdG) predicted long-term mortality from type 2 diabetes in a recent study (Broedbaek et al, 2011). Although all three markers are considered indicators of oxidative stress, they do not always correlate with one another (Watters et al, 2009), and they may differ for several reasons – e.g., DNA, RNA and lipids differ in their proximity to mitochondria, the primarily producer of ROS, they employ different mechanisms of repair or elimination, and each damage signature may have different pathophysiological consequences (Furukawa et al, 2004; Poulsen et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity

Aschbacher

O’Donovan

Wolkowitz

et al. 2013

Psychoneuroendocrinology

368

256

View full text Add to dashboard Cite

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F2α (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-OxoG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as “peak” cortisol reactivity, while the increase from 0 to 15 min was defined as “anticipatory” cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01.) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the Hypothalamic-Pituitary-Adrenal axis. It also supports the less studied model of ‘eustress’ - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.

show abstract

“…Elevated markers of oxidative stress are associated with human obesity (Keaney et al, 2003), diabetes (Keaney et al, 2003), and cardiovascular mortality (Roest et al, 2008). Further, 8-hydroxyguanosine (8-oxoG), a marker of RNA oxidation, prospectively predicts long-term mortality among patients with diabetes (Broedbaek et al, 2011). Chronic psychological stress (e.g., caring for a spouse with dementia) has also been associated with heightened levels of both 8-oxoG and the oxidative byproduct F2-Isoprostanes (Epel et al, 2004b; Aschbacher et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Chronic stress increases vulnerability to diet-related abdominal fat, oxidative stress, and metabolic risk

Aschbacher¹,

Kornfeld²,

Picard³

et al. 2014

Psychoneuroendocrinology

111

View full text Add to dashboard Cite

Summary Background In preclinical studies, the combination of chronic stress and a high sugar/fat diet is a more potent driver of visceral adiposity than diet alone, a process mediated by peripheral Neuropeptide Y (NPY). Methods In a human model of chronic stress, we investigated whether the synergistic combination of highly palatable foods (HPF; high sugar/fat) and stress was associated with elevated metabolic risk. Using a case-control design, we compared 33 post-menopausal caregivers (the chronic stress group) to 28 age-matched low-stress control women on reported HPF consumption (modified Block Food Frequency Questionnaire), waistline circumference, truncal fat ultrasound, and insulin sensitivity using a three-hour oral glucose tolerance test. A fasting blood draw was assayed for plasma NPY and oxidative stress markers (8-hydroxyguanosine and F2-Isoprostanes). Results Among chronically stressed women only, greater HPF consumption was associated with greater abdominal adiposity, oxidative stress, and insulin resistance at baseline (all p’s ≤.01). Furthermore, plasma NPY was significantly elevated in chronically stressed women (p<.01), and the association of HPF with abdominal adiposity was stronger among women with high versus low NPY. There were no significant predictions of change over one-year, likely due to high stability (little change) in the primary outcomes over this period. Discussion Chronic stress is associated with enhanced vulnerability to diet-related metabolic risk (abdominal adiposity, insulin resistance, and oxidative stress). Stress-induced peripheral NPY may play a mechanistic role.

show abstract

Urinary Markers of Nucleic Acid Oxidation and Long-Term Mortality of Newly Diagnosed Type 2 Diabetic Patients

Cited by 96 publications

References 8 publications

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity

Chronic stress increases vulnerability to diet-related abdominal fat, oxidative stress, and metabolic risk

Contact Info

Product

Resources

About