Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

Abstract

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.

Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms

“…Moreover, an elevated frequency of micronuclei was found in T2D patients with no microvascular or macrovascular complications [132]. Recently, micronuclei frequency was positively related to glycated hemoglobin (HbA1c) levels, as well as to fasting plasma glucose in T2D [133].…”

Activation of Nrf2 signaling by natural products-can it alleviate diabetes?

“…While the underlying pathways and mechanisms are not fully and unambiguously identified yet, it can be assumed that redox stress, protein stress and inflammation, as met in diabetes, may favor cancer initiation and promotion. The constant promitogenic signals provided by hyperinsulinemia and the facilitated supply of glucose for highly glycolytic cancer cells may further pamper the growth and survival of malignant cells (Grindel et al, 2017; Gristina et al, 2015; Hua et al, 2016; Joshi et al, 2015; Reuter et al, 2010). Of note, metformin, one of the first line medications in type 2 DM has been reported to possess anti-cancer properties (Whitburn et al, 2017; Yu et al, 2017; Zhou et al, 2017) supporting common targets and deregulations in cancer and diabetes.…”

Activating the Anaphase Promoting Complex to Enhance Genomic Stability and Prolong Lifespan

“…It is thought that a somatic cell may receive as many as 100,000 lesions daily [ 45 , 46 ]. It is not a coincidence that most age-dependent diseases, such as cancer, type II diabetes, and cardiopulmonary and neurodegenerative diseases are associated with increasingly elevated levels of genomic instability that occur over time [ 47 , 48 , 49 , 50 , 51 ]. When a cell is born, it is presumably at its functional apex, performing at its highest level.…”