Urinary markers of nucleic acid oxidation increase with age, obesity and insulin resistance in Danish children and adolescents

PURPOSE: Oxidative stress may play an important role in childhood obesity and increased cardiometabolic risk. 8-oxo-7,8-dihydroguanosine (8-oxoGuo) from oxidation of RNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) from oxidation of DNA are excreted into urine and function as biomarkers for oxidative stress reflecting the modification rate of nucleic acids by oxidation. This study investigates the associations between urinary markers of nucleic acid oxidation and Body Mass Index (BMI), age, sex and cardiometabolic risk factors in children and adolescents with and without obesity.

METHODS: We studied 543 children and adolescents from an obesity clinic cohort (n = 418) and a population-based cohort (n = 125), all aged 6-18 years. Anthropometrics, urine and blood samples were collected. A validated liquid chromatography-tandem mass spectrometry method was used to measure the nucleic acid oxidation markers.

RESULTS: Compared with the population-based cohort, children and adolescents in the obesity clinic cohort had higher calculated 24-h excretion of 8-oxoGuo (p = 0.045) and 8-oxodG (p = 0.014) adjusted for basal metabolic rate. Both oxidation markers were positively associated with age and female sex (all p < 0.002). In the obesity clinic cohort the RNA oxidation marker 8-oxoGuo correlated with serum insulin (rho = 0.18, p = <.001) and insulin resistance (rho = 0.19, p = <.001).

CONCLUSIONS: Childhood obesity associate with higher urinary excretion of nucleic acid oxidation biomarkers, and increase with age throughout childhood, mirroring the obesity- and age-related increase shown in adults. Finally, children with obesity and insulin resistance had higher RNA oxidation markers than children with obesity and no insulin resistance, supporting a possible link between oxidative stress and the pathogenesis of cardiometabolic risk including type 2 diabetes.