8-hydroxy-2--deoxyguanosine and Prediabetic-State

Polycyclic aromatic hydrocarbons (PAHs) are key air pollutants that may contribute to the risk of numerous diseases by inducing inflammation and oxidative stress. Individuals with metabolic disorders may be more susceptible to PAH-induced inflammation and oxidative stress. To test this hypothesis, we designed a panel study involving 60 patients with pre-type 2 diabetes (pre-T2D) and 60 reference participants, and conducted up to seven repeated clinical examinations. Urinary metabolites of PAHs (i.e., OH-PAHs), measured as indicators of total PAH exposure, showed significant associations with markers of respiratory and systemic inflammation, including exhaled nitric oxide, interleukin (IL)-6 in exhaled breath condensate, and blood IL-2 and IL-8 levels and leucocyte count. The most significant effect was on urinary malondiadehyde (MDA), a marker of lipid peroxidation; a onefold increase of OH-PAHs was associated with 9.2-46.0% elevation in MDA in pre-T2D participants and 9.8-31.2% increase in healthy references. Pre-T2D participants showed greater increase in MDA, suggesting that metabolic disorder enhanced the oxidative damage induced by PAH exposure. This study revealed the association between PAH exposure and markers of inflammation and oxidative stress, and the enhanced responses of pre-T2D patients suggested that individuals with metabolic disorders were more susceptible to the adverse health effects of PAH exposure.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Deoxyguanosine; Diabetes Mellitus, Type 2; Environmental Exposure; Environmental Pollutants; Female; Humans; Inflammation; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Polycyclic Aromatic Hydrocarbons; Prediabetic State

Sirtuins (SIRTs) is a family of NAD

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Down-Regulation; Female; Humans; Male; Middle Aged; Oxidative Stress; Prediabetic State; Sirtuins

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

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Chromatography, Liquid; Deoxyadenosines; Deoxyguanosine; Diabetes Mellitus, Type 2; Dinoprost; DNA Damage; Female; Glycated Hemoglobin; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Prediabetic State; Tandem Mass Spectrometry; Triglycerides

This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls.. Participants attended the School of Community Health, Diabetes Screening Clinic, Charles Sturt University, Australia, between February 2006 and June 2008. A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds.. Serum 8-hydroxy 2'-deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3±140 pg/ml) compared with controls (210.1±166 pg/ml; P<0.01). The diabetic group (1979.6±1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5±103 pg/ml; P<0.001) and overweight subjects (724±102 pg/ml; P=0.005) compared with the lean subjects (196.5±327 pg/ml).. Our results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol, HDL; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Female; Free Radicals; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Multivariate Analysis; Obesity; Oxidative Stress; Prediabetic State; Sex Characteristics

Several studies have shown increased oxidative stress in patients with pre-diabetes and newly diagnosed Type 2 diabetes mellitus (T2DM). It has been proposed that oxidative stress initiates insulin resistance in genetically predisposed individuals. The aim of this study was to evaluate the markers of oxidative stress in the offspring of patients with T2DM.. We examined 60 lean normoglycemic offspring of Type 2 diabetics, and 52 age, sex and body mass index matched subjects without family history of T2DM as controls. Anthropometric, biochemical and carotid intima media thickness (IMT) measurements and oral glucose tolerance test (OGTT) were performed. Erythrocyte superoxide dismutase and glutathione peroxidase activities, serum nitric oxide, plasma total sulfhydryl (tSH) groups, plasma total antioxidant status, plasma malondialdehyde and serum 8-hydroxydeoxy-guanosine (8-OHdG) levels were compared between 2 groups.. 2 groups were similar for the measurements of anthropometric, blood pressure, lipids, fasting glucose, HOMA-IR and carotid IMT. Glucose levels during OGTT were significantly higher in the offspring of Type 2 diabetics than controls (p=0.035). The offspring of Type 2 diabetics showed a significant increase in serum 8-OHdG level (p=0.005) and plasma tSH groups (p=0.032) when compared to the controls. Significant differences were not obtained in other oxidative stress marker levels between 2 groups.. Main finding of our study was the presence of increased oxidative DNA damage in lean normoglycemic offspring of Type 2 diabetic patients. There is a need for further clinical studies in order to explain whether oxidative stress is present in genetically predisposed subjects and induces the insulin resistance.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Blood Glucose; Body Mass Index; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Family Health; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Oxidative Stress; Parents; Prediabetic State; Sulfhydryl Compounds; Thinness; Young Adult

Rising levels of oxidative stress play an important role in the pathogenesis of type 2 diabetes mellitus. Therefore, we investigated the serum level of 8-hydroxy-2-deoxy-guanosine (8-OHdG) as an early oxidative stress marker in patients with prediabetes and with type 2 diabetes mellitus.. Convenience sampling from people attending a diabetes screening clinic. Participants at the rural diabetes screening clinic had their medical history recorded as well as body mass index, blood glucose, cholesterol, glutathione, malondialdehyde, fasting blood glucose and 8-OHdG measured. Statistical analysis was performed using ANOVA followed by Sheffe posthoc test for between-group differences.. The 8-OHdG level was significantly greater in the prediabetes (516.5 +/- 260 pg/ml) compared to control group (177.8 +/- 91 pg/ml; P < 0.01). The diabetes group (1926.9 +/- 1197 pg/ml) had the highest level of 8-OHdG, being approximately four times greater compared to the prediabetes group (P < 0.001). No significant change in the cholesterol profile, MDA level indicative of lipid peroxidation and antioxidant activity as measured by erythrocyte reduced glutathione was observed in the prediabetes group compared to the control group (P > 0.05).. 8-OHdG levels in both the prediabetes and diabetes group were increased from control values suggesting a role for 8-OHdG as an early disease marker that may be more sensitive compared to cholesterol, MDA and erythrocyte reduced glutathione levels, which were within normal limits. This is of clinical significance as 8-OHdG is a strong indicator of oxidative stress related DNA damage within blood vessel walls and other tissue that increases the risk of cardiovascular disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Case-Control Studies; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Female; Humans; Male; Malondialdehyde; Middle Aged; Prediabetic State