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Elevated urinary levels of 8-oxo-2′-deoxyguanosine, (5′R)- and (5′S)-8,5′-cyclo-2′-deoxyadenosines,and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes
Institution:1. From the Department of Nuclear Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.;2. Department of Gastrointestinal Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.;3. Department of Endocrinology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.;1. Servicio de Cardiología, Complejo Hospitalario Universitario de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela 15706, Spain;2. Departamento de Enfermería, Universidad de Santiago de Compostela, Santiago de Compostela 15782, Spain;3. Departamento de Medicina, Universidad de Santiago de Compostela, Santiago de Compostela 15782, Spain;1. Internal Medicine and Center of Excellence on Aging, “G. d''Annunzio” University Foundation, Chieti, Italy;2. Nephrology and Dialysis Unit, “S. Massimo” Hospital, Penne, Italy;3. Italian Society of General Practitioners (SIMG), Italy;4. Nephrology and Dialysis Unit, “G. Mazzini” Hospital, Teramo, Italy;5. Internal Medicine Unit, Ortona-Guardiagrele Hospital, Italy;6. San Raffaele Rome Open University, IRCCS San Raffaele Pisana, Rome, Italy
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 F (8-iso-PGF) 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-PGF was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF were 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-PGF levels 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.
Keywords:Oxidatively induced DNA damage  Lipid peroxidation  Prediabetes  8-Oxo-2′-deoxyguanosine
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