Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in
Etiane Tatsch1, José A M De Carvalho2, Bruna S Hausen1
1Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
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.
Insights
Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) levels indicate increased oxidative DNA damage in type 2 diabetes (T2DM). Higher 8-OHdG correlates with greater inflammation, insulin resistance, and microvascular complications in T2DM patients.
Area of Science:
- Biochemistry
- Endocrinology
- Molecular Biology
Background:
- Oxidative DNA damage is elevated in type 2 diabetes mellitus (T2DM).
- The relationship between DNA damage, inflammation, and insulin resistance in T2DM is not fully understood.
- Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) is a marker of nucleic acid oxidation.
Purpose of the Study:
- To investigate the association between urinary 8-OHdG levels and inflammatory cytokines (IL-6, IL-1, TNF-α, IL-10) and insulin resistance (HOMA-IR) in T2DM.
- To evaluate the diagnostic capability of urinary 8-OHdG in identifying microvascular complications in T2DM.
- To explore the cascade of events linking metabolic abnormalities, inflammation, and DNA damage in T2DM.
Main Methods:
- A case-control study comparing 54 T2DM patients with 22 healthy controls.
- Measurement of urinary 8-OHdG, serum inflammatory cytokines (IL-6, IL-1, TNF-α, IL-10), and HOMA-IR.
- Statistical analysis to assess correlations and diagnostic accuracy (AUC).
Main Results:
- T2DM patients exhibited higher urinary 8-OHdG, IL-6, IL-1, TNF-α, and HOMA-IR, with lower IL-10 compared to controls.
- Urinary 8-OHdG levels were significantly elevated in T2DM patients with microvascular complications.
- Urinary 8-OHdG demonstrated a higher diagnostic ability (AUC=0.836) for microvascular complications than urinary albumin (AUC=0.786).
- Higher urinary 8-OHdG correlated with increased IL-6, TNF-α, HOMA-IR, and decreased IL-10.
Conclusions:
- Increased urinary 8-OHdG reflects greater inflammation and insulin resistance in T2DM.
- Urinary 8-OHdG is a promising biomarker for assessing oxidative stress and microvascular complications in T2DM.
- T2DM may involve a cascade of metabolic abnormalities, inflammation, and increased reactive oxygen species leading to DNA damage.
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