title: Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2αas potential biomarkers of oxidative stress in patients with prediabetes.
abstract: Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, β-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F2α(8-iso-PGF2α) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF2αwas achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF2αwere significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbA1c were found negatively correlated in prediabetes patients. Also 8-iso-PGF2αlevels and HbA1c were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated in prediabetic stage may be used as early disease markers in patients at risk for T2DM.
authors: Department of Medical Biochemistry, Institute of Health Sciences, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey. Electronic address: melissdinc@gmail.com.
authors: Melis
authors: M
authors: Kant
authors: Department of Medical Biochemistry, Institute of Health Sciences, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey.
authors: Merve
authors: M
authors: Akış
authors: Division of Endocrinology, Izmir Bozkaya Research and Education Hospital, 35170, Izmir, Turkey.
authors: Mehmet
authors: M
authors: Çalan
authors: Division of Endocrinology, Derince Research and Education Hospital, 41900, Kocaeli, Turkey.
authors: Tuğba
authors: T
authors: Arkan
authors: Department of Internal Medicine, Division of Endocrinology and Metabolism, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey.
authors: Fırat
authors: F
authors: Bayraktar
authors: Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors: Miral
authors: M
authors: Dizdaroglu
authors: Department of Medical Biochemistry, Institute of Health Sciences, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey; Department of Molecular Medicine, Institute of Health Sciences, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey.
authors: Hüray
authors: H
authors: İşlekel
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002853:Chromatography, Liquid; D004249:DNA Damage; D003839:Deoxyadenosines / Q000652:urine*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011236:Prediabetic State / Q000175:diagnosis* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods; D014280:Triglycerides / Q000097:blood
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers; D002097:C-Reactive Protein; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003839:Deoxyadenosines; D003849:Deoxyguanosine; D015237:Dinoprost; D006442:Glycated Hemoglobin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C056752:8,5'-cyclo-2'-deoxyadenosine; C075750:8-epi-prostaglandin F2alpha
keywords: 8,5′-cyclo-2′-Deoxyadenosines; 8-Oxo-2′-deoxyguanosine; 8-iso-Prostaglandin F(2α); Lipid peroxidation; Oxidatively induced DNA damage; Prediabetes