Urinary nucleic acid oxidation product levels show differential associations with pharmacological treatment in patients with type 2 diabetes

Abstract

The relationship between RNA and DNA oxidation and pharmacological treatment has not been systematically investigated in patients with type 2 diabetes (T2D). We aimed to investigate the association between pharmacological treatments and levels of urinary markers of nucleic acid oxidation in T2D patients. Vejle Diabetes Biobank cohort data was nested into nationwide registry data. Multiple logistic regression was used to associate drug usage with risk of high (above median) RNA and DNA oxidation. Data from 2664 T2D patients (64% male, age range: 25–75) were included. Questionnaire-validated lipid lowering drug use was associated with low RNA oxidation (Odds ratio, OR 0.71, 95% CI: [0.59–0.87]). Insulin and non-specific antidiabetic drugs were associated with low DNA oxidation (insulin: OR 0.60, 95% CI [0.49–0.73]). Oral antidiabetics were associated with high DNA oxidation and RNA oxidation (OR 1.30, 95% CI [1.10–1.53] and OR 1.26, 95% CI [1.07–1.29]). Our findings indicate that diabetes-related drugs are associated with RNA and DNA oxidation and further studies are required to determine causality in T2D patients.

Keywords:

• 8-Oxo-7,8-dihydro-2-deoxyguanosine
• 8-oxo-7,8-dihydroguanosine
• clinical pharmacology
• oxidative stress
• type 2 diabetes

Acknowledgements

We thank Katja Luntang Christensen for assisting T.H. with the urinary analyses of 8-oxoGuo and 8-oxodG. The Novo Nordisk Foundation Centre for Basic Metabolic Research is an independent research centre at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation.

Disclosure statement

C.T-P. reports grants and personal fees from Bayer Pharmaceuticals, grants from Biotronic, outside the submitted work. None of the other authors declare competing interests.

Additional information

Funding

This study was funded by the Toyota Foundation Denmark and the Research Committee of the Capital Region of Denmark. The Vejle Diabetes Biobank was supported by the Danish Council for Independent Research/Medical Sciences; the Research Council of Vejle Hospital, the Department of Internal Medicine, Vejle Hospital, Vejle County, Denmark; the Danish Research Fund; the Lions Club International Denmark; and anonymous donations. V.C. was funded by the Faculty PhD Scholarship from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. The Novo Nordisk Foundation Centre for Basic Metabolic Research is an independent Research Centre at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).