Pylov D. Optimization of diagnosis and treatment of patients with type 2 diabetes mellitus and chronic pancreatitis based on the assessment of the pathogenetic role of vaspin

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U101867

Applicant for

Specialization

  • 222 - Медицина

17-06-2021

Specialized Academic Board

ДФ 64.600.029

Kharkiv National Medical University

Essay

The dissertation is devoted to the study of the peculiarities of changes in lipid and carbohydrate metabolism, the functional state of the pancreas (PC), the state of the intima-media complex of the common carotid arteries (IMC CA) and adipokines - vaspin and TNF-α to determine markers of risk of cardiovascular disease. can be used to increase and evaluate the effectiveness of complex therapy of patients with chronic pancreatitis (CP), type 2 diabetes mellitus (DM-2) and combined pathology. Enrolled 114 patients with CP and DM-2, 27.2% - patients with DM-2, 20.2% - patients with CP and 52.6% of patients with combined pathology. Control group - 20 healthy individuals. It was found that in patients with isolated CP and DM-2 in combination with CP, data were obtained on the violation of exocrine secretion of the pancreas, which worsened in the presence of comorbid pathology. It was found increased levels of glycaemia, α-amylase in the blood, C-reactive protein (CRP) and decreased fecal elastase-1 (FE-1), which are interdependent changes. Dyslipidemia were obtained in patients with DM-2. When determining the status of IMC CA in the involved patients, it was found that the addition of CP to the DM-2 can lead to an increase in the thickness of IMC CA and increase the development of atherosclerotic lesions. Endocrine dysfunction of the PC has atherogenic effect. It was found that in patients with DM-2 atherosclerotic plaque (ASP) was characterized by active growth and in combination with CP due to the inflammatory process, manifestations of atherosclerosis were expressed in the form of increased fragile heterogeneous ASP. The combination of DM-2 and CP leads to a deterioration in lipid metabolism which accelerates the progression of atherosclerosis. It was found an increase of the level of vaspin and TNF-α in patients with DM-2 and CP, and a decrease the level of vaspin with increase the level of TNF-α in patients with combined pathology. An increase of TNF-α and a decrease of vaspin in combined pathology is a sign of weakening of the body's compensatory capabilities. The obtained data confirm the role of the cytokine link in the development of protective imbalance. A significant correlation was found between the level of vaspin and TNF-α, which had a different tendency depending on the pathology. To determine in more detail the role of vaspin in the occurrence and course of comorbid conditions, a mathematical model was created to predict changes in vaspin levels in patients of the groups and among indicators of carbohydrate, lipid metabolism, inflammatory markers and functional status of the PC and define impact parameters (IP) associated with the of vaspin, to predict of atherogenesis. The analysis of the IP substantiated the regression model with the definition of changes in the leading criteria and markers for predicting the values of vaspin. The group with comorbid pathology had indicators that are a key part of the IP on the level of vaspin in patients with DM-2 and CP (FPG,IRI,FE-1,TNF-α,CRP,TG,LDL) and added a new parameter - ASP. The combination of exo- and endocrine disorders enhances the mechanisms of insulin resistance and atherogenesis. Obtained in the studied IP for vaspinemia are parameters that participate in atherogenesis and affect its activity. That is why content of vaspine in patients with DM-2 and CP can be considered as a potential marker of cardiovascular disorders. The relationship between vaspin levels and ASP was found. The value of vaspin affects atherogenesis, so based on the study to predict the risk of cardiovascular disorders in patients with DM-2 and CP a mathematical model of atherogenesis was created. To create a mathematical model for predicting the occurrence of cardiovascular pathology in patients with DM-2 and CP, among the indicators studied in the study the growth markers of IMC CA were established. As a result, it was found that a decrease in the ratio of vaspin/TNF-α below 0.5pg/ml can be used as a marker of early atherosclerotic lesions of the vascular wall of the common carotid artery. To optimize the treatment of DM-2 patients and CP, a scheme of therapy using α-lipoic acid (ALA) was used. The feasibility of therapy is determined by the dynamics of adipokines, carbohydrate and lipid metabolism parameters and the thickness of IMC CA in DM-2 and CP patients. There was an improvement in carbohydrate and lipid metabolism, an increase in the level of vaspin, a decrease in the level of TNF-α during therapy and a tendency to decrease the thickness of the IMC CA. The significance of the obtained results lies in the scientific substantiation of the pathogenetic role of vaspin in comorbid conditions in patients with DM-2 and CP based on the assessment of carbohydrate, lipid metabolism, functional status of the PC to determine atherogenesis markers to increase the effectiveness of treatment of patients with DM-2 and CP.

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