Abstract
Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB-indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes.
Highlights
Obesity increases the risk of progression to metabolic syndrome, type 2 diabetes, cardiovascular- and liver disease, as well as certain cancers and is generally associated with an increased all-cause mortality rate [1, 2]
This paper reports our findings from a study in a large cohort of 356 patients, where we aimed to examine if a reduction in oxidative stress level could be detected within the first two years after Roux-en-Y gastric bypass (RYGB)-surgery
We aimed to find out if there were differences in the levels of the urinary markers between patient subgroups based on diabetes status and if levels differed before or after surgery depending on the outcome after surgery on the diabetic condition
Summary
Obesity increases the risk of progression to metabolic syndrome, type 2 diabetes, cardiovascular- and liver disease, as well as certain cancers and is generally associated with an increased all-cause mortality rate [1, 2]. A combination of increased inflammation and oxidative stress, induced by obesity, is suggested to be causative [2,3,4]. Broadly defined as an imbalance in the body’s naturally occurring oxidation- and reduction processes which leads to a net increase in concentrations of highly reactive oxygen species (ROS) [5], further seems to accelerate the development of micro- and macrovascular complications in patients with diabetes [6]. Damage caused by ROS are kept at a minimum through the acts of the body’s own defense system [5]. The products of the repair-mechanisms controlling oxidative damage to nucleic acids can be assessed in urine as the markers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
