title: Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in type 2 diabetes.
abstract: 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.
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Etiane
authors.initials: E
authors.lastname: Tatsch
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; University Hospital, Santa Maria, RS, Brazil.
authors.forename: José A M
authors.initials: JA
authors.lastname: De Carvalho
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Bruna S
authors.initials: BS
authors.lastname: Hausen
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Yãnaí S
authors.initials: YS
authors.lastname: Bollick
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: Torbitz
authors.affiliation: Laboratory of Biogenomic, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Duarte
authors.affiliation: Labimed Clinical Chemistry and Medicine Laboratory, Santa Maria, RS, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: Scolari
authors.affiliation: Labimed Clinical Chemistry and Medicine Laboratory, Santa Maria, RS, Brazil; Department of Health Sciences, Universidade Luterana do Brasil, Santa Maria, RS, Brazil.
authors.forename: Marta M M F
authors.initials: MM
authors.lastname: Duarte
authors.affiliation: University Hospital, Santa Maria, RS, Brazil.
authors.forename: Sílvia W K
authors.initials: SW
authors.lastname: Londero
authors.affiliation: Laboratory of Microbiology, Franciscan University Center, UNIFRA, Santa Maria, RS, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Vaucher
authors.affiliation: Department of Clinical Medicine, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Melissa O
authors.initials: MO
authors.lastname: Premaor
authors.affiliation: Department of Clinical Medicine, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Fabio V
authors.initials: FV
authors.lastname: Comim
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address: rnmoresco@ufsm.br.
authors.forename: Rafael N
authors.initials: RN
authors.lastname: Moresco
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000276:immunology; D003925:Diabetic Angiopathies / Q000235:genetics / Q000276:immunology / Q000652:urine; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics* / Q000276:immunology; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D016207:Cytokines; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: DNA damage; Inflammation; Insulin resistance; Type 2 diabetes