Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in type 2 diabetes.
Urinary markers of nucleic acid oxidation may be useful biomarkers in diabetes. It has been demonstrated that T2DM patients have an increased level of oxidative DNA damage; however, it is unclear whether increased DNA damage may be related to a greater degree of inflammation and insulin resistance. Thus, the aim of this present study was to investigate the relation of the impact of oxidative DNA damage, assessed by urinary 8-OHdG, on the levels of inflammatory cytokines, as well as insulin resistance. In addition, we also investigated the diagnostic ability of urinary 8-OHdG in the identification of microvascular complications in T2DM.A case-control study, enrolling 22 healthy controls and 54 subjects with T2DM, was performed to evaluate the relation between oxidative DNA damage and interleukin-6 (IL-6), IL-1,tumor necrosis factor-alpha (TNF-α), IL-10, and Homeostasis Model Assessment (HOMA-IR) index. T2DM patients presented higher urinary 8-OHdG, IL-6, IL-1, TNF-α levels and HOMA-IR, and lower IL-10 levels than control subjects. Moreover, urinary 8-OHdG levels were significantly higher in the group T2DM with microvascular complications when compared to the without complications. The areas under the curve for urinary 8-OHdG and urinary albumin were, respectively, 0.836 (P<0.001) and 0.786 (P=0.002). Thus, urinary 8-OHdG has a slightly higher ability to discriminate microvascular complications in T2DM compared with urinary albumin. It was also demonstrated that T2DM patients with higher median of urinary 8-OHdG had significantly elevated levels of IL-6, TNF-α and HOMA-IR, and decreased IL-10 levels. Our findings showed that T2DM patients with higher urinary 8-OHdG levels showed a greater inflammatory degree and higher insulin resistance. It is possible to speculate that T2DM patients present a cascade of events as increasing metabolic abnormalities such as insulin resistance and inflammatory activation, as well as increased ROS generation factors that may contribute directly to greater oxidative DNA damage.
['Tatsch|Etiane|E|', 'De Carvalho|José A M|JA|', 'Hausen|Bruna S|BS|', 'Bollick|Yãnaí S|YS|', 'Torbitz|Vanessa D|VD|', 'Duarte|Thiago|T|', 'Scolari|Rogério|R|', 'Duarte|Marta M M F|MM|', 'Londero|Sílvia W K|SW|', 'Vaucher|Rodrigo A|RA|', 'Premaor|Melissa O|MO|', 'Comim|Fabio V|FV|', 'Moresco|Rafael N|RN|']
D000080242:8-Hydroxy-2'-Deoxyguanosine D015415:Biomarkers D016022:Case-Control Studies D016207:Cytokines D004249:DNA Damage D003849:Deoxyguanosine D003924:Diabetes Mellitus, Type 2 D003925:Diabetic Angiopathies D005260:Female D006801:Humans D007333:Insulin Resistance D016014:Linear Models D008297:Male D055806:Microvessels D008875:Middle Aged D018384:Oxidative Stress D012372:ROC Curve
DNA damage Insulin resistance Type 2 diabetes Inflammation