Abstract
BackgroundDiabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration.MethodsFemale T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals.ResultsNo significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group.ConclusionBMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.
Highlights
Diabetes mellitus type 2 (T2DM) with its resulting complications is one of the biggest preventable health problems of the 21st century and has developed to a major challenge for the health system as one of the fastest increasing diseases worldwide [1]
No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found
A significant up-regulation in mRNA expression was found for APEX1, ligase 3 (LIG3) and X-ray repair cross-complementing protein 1 (XRCC1) in patients with >7.5% HbA1c
Summary
Diabetes mellitus type 2 (T2DM) with its resulting complications is one of the biggest preventable health problems of the 21st century and has developed to a major challenge for the health system as one of the fastest increasing diseases worldwide [1]. Chronic hyperglycemia promotes oxidative stress [7, 8] which represent a major pathophysiological link between progression of T2DM and the onset of severe diabetic complications such as diabetic foot ulcers, myocardial infarction or cerebrovascular accidents [9]. Patients with diabetes mellitus show an increased cancer incidence, with a strong linear association between HbA1c levels and gastric-, pancreatic-, colorectal-, breast- and liver cancer incidence [12, 13]. Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration
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