Kant Melis, Akış Merve, Çalan Mehmet, Arkan Tuğba, Bayraktar Fırat, Dizdaroglu Miral, İşlekel Hüray
Department of Medical Biochemistry, Institute of Health Sciences, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey.
Department of Medical Biochemistry, Institute of Health Sciences, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey.
DNA Repair (Amst). 2016 Dec;48:1-7. doi: 10.1016/j.dnarep.2016.09.004. Epub 2016 Sep 26.
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.
糖尿病前期是2型糖尿病（T2DM）的临床前期阶段，处于血糖异常的中间状态。高血糖会导致氧化应激状态，这可能会促使胰岛素抵抗、β细胞功能障碍以及糖尿病的长期并发症的产生。糖尿病的预防和治疗需要新的方法。需要能够作为当前参数补充用于风险分层和治疗控制的新生物标志物。这些生物标志物可能有助于实现更个体化、更充分的糖尿病治疗。因此，本研究的目的是调查氧化诱导的DNA损伤产物8-氧代-2'-脱氧鸟苷（8-氧代-dG，也称为8-羟基-dG）、（5'R）-和（5'S）-8,5'-环-2'-脱氧腺苷（R-cdA和S-cdA）以及脂质过氧化产物8-异前列腺素F（8-异-PGF）的水平，将其作为糖尿病前期或T2DM患者与健康志愿者相比的可靠氧化应激标志物。从这些受试者收集尿液样本。通过液相色谱-同位素稀释串联质谱法对8-氧代-dG、R-cdA、S-cdA和8-异-PGF进行绝对定量。糖尿病前期患者的8-氧代-dG、S-cdA和8-异-PGF水平显著高于健康志愿者。T2DM患者的8-氧代-dG水平也高于健康志愿者。R-cdA水平未观察到统计学显著差异。糖尿病前期和新诊断的T2DM患者中，8-氧代-dG水平与R-cdA和S-cdA水平呈正相关。糖尿病前期患者中发现S-cdA水平与糖化血红蛋白（HbA1c）呈负相关。糖尿病前期患者中还发现8-异-PGF水平与HbA1c呈负相关。这些结果表明，氧化诱导的大分子损伤在T2DM确立之前就已出现。因此，我们的数据表明，在糖尿病前期阶段发现升高的氧化诱导的DNA损伤和脂质过氧化产物可作为T2DM高危患者的早期疾病标志物。
