Association of elevated frequency of micronuclei in peripheral blood lymphocytes of type 2 diabetes patients with nephropathy complications

Abstract

The increasing incidence of type 2 diabetes mellitus globally has increased the incidence of diabetes-associated complications such as nephropathy. DNA damage induced by oxidative stress might be one of the important mechanisms in the pathogenesis of diabetic complications. Two hundred Iranian individuals with the conditions of type 2 diabetes, diabetic nephropathy and nephropathy patients with no sign of diabetes and normal unaffected sex- and age-matched controls (50 in each group) were enrolled in the study. The background and the net levels of micronucleus (MN) formation as well as other cellular damages induced after in vitro treatment with 25 μg/ml of bleomycin (BLM) were evaluated using cytokinesis block MNs cytome assay (CBMN cyt) in peripheral blood lymphocytes. The background and net BLM-induced levels of MNs were significantly higher in all patient groups compared with the control (P < 0.01, P < 0.001, respectively). The frequency of MNs was significantly higher in those patients with prior incidence of nephropathy than those without. A positive association was observed between basal and net MN frequency among study groups and also between net genetic damages and serum creatinine value and duration of diabetes. The rate of basal and net apoptosis was significantly higher in patients with hyperglycemia. Our results indicate that increased genomic instability expressed as MNs is associated with nephropathy in all pathological stages. Therefore, implementation of MN assay in clinical level may potentially enhance the quality of management of patients with diabetes and its complications such as nephropathy.