Keywords
oncogenesis
hyperinsulinemia
insulin signaling
PI3K/Akt/mTOR
How to Cite
Abstract
Introduction. Numerous studies have proven the link between diabetes and cancer. Chronic metabolic disorders in type 2 diabetes (T2D) cause dysregulation of intracellular systems involved in the control of cell survival, apoptosis, and proliferation. The search for markers of activation of carcinogenesis continues.
Aim. To develop a method for assessing the activation of oncogenesis processes in patients with T2D by creating a mathematical model that takes into account the complex impact of metabolic disorders and the activity of components of insulin signaling PI3K/Akt/mTOR.
Materials and methods. The study involved 28 patients with T2D, and the control group consisted of 16 practically healthy individuals. The examination of patients included determining indicators that reflect carbohydrate metabolism compensation (glycemia, glycated hemoglobin (HbA1c)), levels of growth factors (insulin, IGF-1), and indicators of insulin signaling activity, such as phospho-PRAS40 and phospho-p70S6K. Statistical analysis of the results was performed using STATISTIKA-12 software (StatSoft Inc., USA) and the statistical functions package in Microsoft Excel. Using the obtained data, a mathematical model for assessing oncogenesis activation processes was developed using discriminant analysis.
Results. In patients with T2D, significantly elevated levels of fasting blood glucose, HbA1c, insulin, IGF-1, and HOMA-IR were observed. Significantly increased levels of phospho-PRAS40 and phospho-p70S6K were detected in peripheral blood mononuclear cells. A mathematical model has been created, which allows patients to be classified into two groups: Group 1 – with hyperactivation of insulin signaling, or Group 2 – without hyperactivation. The most significant indicators in the model are blood glucose, insulin levels, HOMA-IR index, HbA1c.
Conclusions. Discriminant analysis proves the importance of a comprehensive approach to the assessment of the activation of oncogenesis processes in patients with T2D, taking into account the markers of diabetes compensation, insulin sensitivity, and the activity of components of the insulin cascade. The mathematical model confirms the statistically significant influence of hyperglycemia, hyperinsulinemia, and insulin resistance as factors activating the insulin signaling pathway.
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