Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients.
Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c > 7.5% compared to subjects with HbA1c ≤ 7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments.
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
Diabetes Outpatient Clinic, Health Centre South, Vienna, Austria.
Helmut
H
Brath
Institute for Cancer Research, Medical University Vienna, Vienna, Austria.
Armen
A
Nersesyan
Institute for Cancer Research, Medical University Vienna, Vienna, Austria.
Siegfried
S
Knasmueller
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; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D042822:Genomic Instability; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents