Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.
BACKGROUND
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.


METHODS
Female 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.


RESULTS
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, 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.


CONCLUSIONS
BMI, 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.
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.|Research Platform Active Ageing, University of Vienna, Vienna, Austria.
Annemarie
A
Grindel
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.
Bianca
B
Guggenberger
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.
Lukas
L
Eichberger
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.
Christina
C
Pöppelmeyer
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.
Michaela
M
Gschaider
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.
Anela
A
Tosevska
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.
George
G
Mare
School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, QLD, Australia.
David
D
Briskey
Diabetes Outpatient Clinic, Health Centre South, Vienna, Austria.
Helmut
H
Brath
Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, University of Vienna, Vienna, Austria.|Research Platform Active Ageing, University of Vienna, Vienna, Austria.
Karl-Heinz
KH
Wagner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D015992:Body Mass Index; D002374:Catalase / Q000097:blood / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000097:blood / Q000235:genetics; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D000075223:Poly-ADP-Ribose Binding Proteins; D013482:Superoxide Dismutase / Q000097:blood / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
D002374:Catalase; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000072481:DNA Ligase ATP; D011088:DNA Ligases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins; D028441:F2-Isoprostanes; D005978:Glutathione; D005979:Glutathione Peroxidase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D000075223:Poly-ADP-Ribose Binding Proteins; D013482:Superoxide Dismutase; D014280:Triglycerides; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins; C000619371:XRCC1 protein, human; C517652:hemoglobin A1c protein, human; C099252:oxidized low density lipoprotein; C085108:APEX1 protein, human; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human