Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A Prospective Cohort Study

Kjær, Laura Kofoed; Cejvanovic, Vanja; Henriksen, Trine; Petersen, Karsten; Hansen, Torben; Pedersen, Oluf; Christensen, Cramer; Torp‐Pedersen, Christian; Gerds, Thomas Alexander; Brandslund, Ivan; Mandrup‐Poulsen, Thomas; Poulsen, Henrik Enghusen

doi:10.2337/dc17-1150

Cited by 53 publications

(23 citation statements)

References 38 publications

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“…In the ADVANCE prospective trial, increased levels of 8-OHdG were independently associated with all-cause and cardiovascular mortality in 3766 T2DM [95]. In a recent prospective cohort study involving 1863 patients with T2DM, 8-oxoGuo was associated with all-cause mortality and cardiovascular death after multiple regression analysis [96]. Moreover, recent findings suggest that urinary 8-oxoGuo provides additional information about risk to that obtained from urinary albumin and that the combined use of 8-oxoGuo and urinary albumin could be useful for a better identification of patients at risk of CVD and death over a period of 19 years of follow-up [97] (Table 3).…”

Section: Biomarkers Of Oxidative Dna and Rna Damagementioning

confidence: 99%

Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications

Bigagli

Lodovici

2019

Oxidative Medicine and Cellular Longevity

152

103

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Type 2 diabetes (T2DM) and its complications constitute a major worldwide public health problem, with high rates of morbidity and mortality. Biomarkers for predicting the occurrence and development of the disease may therefore offer benefits in terms of early diagnosis and intervention. This review provides an overview of human studies on circulating biomarkers of oxidative stress and antioxidant defence systems and discusses their usefulness from a clinical perspective. Most case-control studies documented an increase in biomarkers of oxidative lipid, protein, and nucleic acid damage in patients with prediabetes and in those with a diagnosis of T2DM compared to controls, and similar findings were reported in T2DM with micro- and macrovascular complications compared to those without. The inconsistence of the results regarding antioxidant defence systems renders difficulty to draw a general conclusion. The clinical relevance of biomarkers of oxidative lipid and protein damage for T2DM progression is uncertain, but prospective studies suggest that markers of oxidative nucleic acid damage such as 8-hydroxy-2′-deoxyguanosine and 8-hydroxyguanosine are promising for predicting macrovascular complications of T2DM. Emerging evidence also points out the relationship between serum PON1 and serum HO1 in T2DM and its complications. Overall, enhanced oxidative damage represents an underlying mechanism of glucose toxicity in T2DM and its related micro- and macrovascular complications suggesting that it may be considered as a potential additional target for pharmacotherapy. Therefore, further studies are needed to understand whether targeting oxidative stress may yield clinical benefits. In this view, the measurement of oxidative stress biomarkers in clinical trials deserves to be considered as an additional tool to currently used parameters to facilitate a more individualized treatment of T2DM in terms of drug choice and patient selection.

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Section: Biomarkers Of Oxidative Dna and Rna Damagementioning

confidence: 99%

Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications

Bigagli

Lodovici

2019

Oxidative Medicine and Cellular Longevity

152

103

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“…The ADVANCE Trial revealed that 8-oxo-2'-deoxyguanosine levels were correlated with all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus (T2DM) (n = 3766) [110]. Likewise, an independent prospective cohort study revealed a correlation of RNA oxidation with all-cause and cardiovascular mortality risk in patients with T2DM [111]. Dapagliflozin therapy conferred better glycemic control, endothelial function, which was associated with lower 8-oxo-2'-deoxyguanosine urine levels in T2DM patients [112].…”

Section: Clinical Evidence For a Role Of Oxidative Stress In Cardiovamentioning

confidence: 99%

Regulation of Vascular Function and Inflammation via Cross Talk of Reactive Oxygen and Nitrogen Species from Mitochondria or NADPH Oxidase—Implications for Diabetes Progression

Daiber

Steven

Kalinovic

et al. 2020

IJMS

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Oxidative stress plays a key role for the development of cardiovascular, metabolic, and neurodegenerative disease. This concept has been proven by using the approach of genetic deletion of reactive oxygen and nitrogen species (RONS) producing, pro-oxidant enzymes as well as by the overexpression of RONS detoxifying, antioxidant enzymes leading to an amelioration of the severity of diseases. Vice versa, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of RONS detoxifying enzymes. We have previously identified cross talk mechanisms between different sources of RONS, which can amplify the oxidative stress-mediated damage. Here, the pathways and potential mechanisms leading to this cross talk are analyzed in detail and highlighted by selected examples from the current literature and own data including hypoxia, angiotensin II (AT-II)-induced hypertension, nitrate tolerance, aging, and others. The general concept of redox-based activation of RONS sources via “kindling radicals” and enzyme-specific “redox switches” as well as the interaction with redox-sensitive inflammatory pathways are discussed. Here, we present evidence for the existence of such cross talk mechanisms in the setting of diabetes and critically assess their contribution to the severity of diabetic complications.

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“…Increased levels of oxidative stress may predict mortality in patients with other chronic diseases such as diabetes 35 . Epidemiological studies have found that the life expectancy among patients with BD is decreased by 8–12 years compared to the general population 36 and that patients die due to natural causes of death already from adolescence 37 .…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study

et al. 2019

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Bipolar disorder (BD) is a mental disorder characterized by recurrent relapses of affective episodes, cognitive impairment, illness progression, and reduced life expectancy. Increased systemic oxidatively generated nucleoside damage have been found in some neurodegenerative disorders and in BD. As the first, this naturalistic prospective, longitudinal follow-up case-control study investigated cerebrospinal fluid (CSF) oxidative stress markers 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) that relate to RNA and DNA damage, respectively. Patients with BD (n = 86, 51% female) and gender-and-age-matched healthy control individuals (HC; n = 44, 44% female) were evaluated at baseline (T0), during (T1) and after a new affective episode (T2), if it occurred, and after a year (T3). Cerebrospinal and urine oxidative stress markers were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. CSF-8-oxoGuo was statistically significantly higher by 18% (p = 0.003) in BD versus HC at T0, and by 22% (p = 0) at T3. CSF-8-oxoGuo had increased by 15% (p = 0.042) from T0 to T3, and by 14% (p = 0.021) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxodG had increased by 26% (p = 0.054) from T0 to T2 and decreased by 19% (p = 0.041) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxoGuo did not show a statistically significant change in HC during the one-year follow-up. CSF and urine-8-oxoGuo levels correlated moderately. In conclusion, CSF oxidative stress marker of RNA damage 8-oxoGuo showed both state and trait dependence in BD and stability in HC. Central RNA damage may be a potential biomarker for BD.

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Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A Prospective Cohort Study

Abstract: We conclude that high RNA oxidation is associated with all-cause and cardiovascular mortality risk in patients with type 2 diabetes. Targeting oxidative stress via interventions with long-term follow-up may reveal the predictive potential of the biomarker 8-oxoGuo.

Cited by 53 publications

References 38 publications

Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications

Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications

Regulation of Vascular Function and Inflammation via Cross Talk of Reactive Oxygen and Nitrogen Species from Mitochondria or NADPH Oxidase—Implications for Diabetes Progression

Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study

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