Object of research: oncological diseases in patients with diabetes mellitus (DM). Objective: to improve the effectiveness of diagnosis and prevention of malignant neoplasms in patients with DM based on the study of leading risk factors, mechanisms of development and characteristics of the course of oncological diseases in patients with DM to determine the main clinical and diagnostic criteria of formation of oncological pathology in this category of patients. Research methods and equipment: epidemiological, general clinical, anthropometric, mathematical, biochemical, enzyme - linked immunosorbent, spectrometric, statistical - parametric and nonparametric. Enzyme-linked immunosorbent assay STAT FAX 303 plus (USA), enzyme-linked immunosorbent assay Bio-tek Instruments 450 (USA), automatic glycosylated haemoglobin D-10 analyser (USA), automatic blood glucose analyser (AGKM-01) (Ukraine).Theoretical and practical results: the paper presents the results of a retrospective-analytical epidemiological study of cancer in patients with DM for the period 2012-2016. An increased risk of developing malignant neoplasms (MN) of the mammary glands, uterine body, and pancreas in women with type 2 diabetes (T2D) as well as pancreatic cancer in men with T2D has been proven. The effect of obesity on the risk of developing of breast cancer in women, prostate and colorectal cancer in men has been demonstrated. The effect of insulin therapy on the risk of developing MN in patients with T2D has been found. The influence of T2D on the survival of patients with MN has been proven. It was found that, in addition to the stage of cancer, the life expectancy of people with T2D is influenced by: the level of glycosylated haemoglobin (HbA1c), the duration of DM and antidiabetic therapy (for certain localizations of cancer of certain stages).The main clinical and diagnostic criteria of the formation of oncological pathology in patients with DM are determined, based on which mathematical models for calculating the individual predicted risk of the most common for T2D MN have been developed. Diagnostic and therapeutic algorithms for patients with T2D with a predicted moderate and high risk of cancer, as well as individual approaches to the examination and treatment of patients with T2D, considering insulin resistance and obesity for the purpose of prevention of cancer were elaborated. The influence of hyperglycaemia, obesity, hyperinsulinemia, and excessive content of insulin-like growth factor-1 (IGF-1) as probable epigenetic factors of oncogenesis in T2D, the effects of which are realized through the PI3K/Akt/mTOR signalling pathway, has been demonstrated. The oncoprotective properties of metformin due to the ability to inhibit the activity of the PI3K/Akt/mTOR pathway have been confirmed. Novelty: the results of the dissertation research present the data of the epidemiological study of oncological diseases in patients with DM, conducted for the first time in Ukraine. Scientific data on the influence of T2D on the formation of oncological pathology have been confirmed. Scientific data on the influence of obesity and insulin therapy on the development of MN in patients with T2D have been supplemented. The effect of antidiabetic therapy, level of HbA1c, duration of DM on the survival of patients with MN have been determined. In patients with T2D, hyperactivation of the PI3K/Akt/mTOR signalling pathway, based on an increase in biochemical markers of its activation: phospho-Akt (Ser473), phospho-p70S6K (Thr389) and phospho-PRAS40 (pT246) has been revealed. The lack of activation of the PI3K/Akt/mTORC1 in patients with MN that were diagnosed on the background of T2D has been proven. The hypothesis of reciprocal phosphorylation of Akt by interaction of PDK-1-dependent phosphorylation of Akt (Thr308) and mTORC2-mediated phosphorylation of Akt (Ser473) in patients with T2D has been proven and scientifically substantiated. The direct effect of hyperglycaemia on the activation of mTORC1 in T2D has been found. For the first time, mathematical models were created to calculate the predicted risk of MN of the most common localizations (breast, uterine, colorectal, and pancreatic cancer) in patients with T2D. For the first time, a mathematical model to assess the activation of processes of oncogenesis that are realized through the PI3K/Akt/mTOR pathway was created. The method of diagnosing T3cDM by DM has been improved; scientific data on indications for pancreatic cancer screening have been expanded. Scientific data on the oncoprotective properties of biguanides based on the proven inhibition of phosphorylation of PRAS40 and p70S6K in patients with T2D receiving metformin monotherapy have been confirmed. Degree of implementation: the results of the study are implemented in the practice of the health care system of Ukraine. Areas of use: endocrinology.
