Михальчишин Г. Pathophysiological mechanisms of the clinical progression variability and system of medical care for the patients with type 2 diabetes mellitus who also have non-alcoholic fatty liver disease.

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0521U101330

Applicant for

Specialization

  • 14.01.14 - Ендокринологія

11-05-2021

Specialized Academic Board

Д 26.631.01

Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine

Essay

In dissertational work a new solution of the scientific-practical problem of modern endocrinology was presented. It will increase the effectiveness of complex medical help to patients with the type 2 diabetes mellitus (T2D) with the nonalcoholic fatty liver disease (NAFLD) on the basis of studying of carbohydrate, lipid, immune and hormonal conditions among patients with different causes of the disease. As the result the strategy of prophylactic and therapeutic measures was created. It tells about the correction of metabolic violations among the patients with T2D, who also have NAFLD. We defined the character of changes and the structure of interconnections between carbohydrate, lipid, hormonal and immunological status of patients with the T2D with NAFLD depending on the level of transaminases. It was demonstrated that the patients with the diagnosed NAFLD have been complaining more frequently than the patients with T2D but without the mentioned pathology. Along with that the progression of NAFLD among the T2D patients depends on a continuance of T2D, its severe form, the existence of complications, such as proliferative retinopathy, nephropathy, macrovascular diseases, such as myocardial infarction. We defined that obesity, carbohydrate metabolism disorder and cytolitic syndrome are the key factors of the progression of NAFLD among patients with the T2D. This was confirmed by a clear connection of the step-by-step multiply logistic regression analysis between the development of NAFLD, BMI and the level of НОМА-ІR and alanine aminotransferase. The role of inflammatory mechanism in the development NAFLD with the T2D is confirmed by the associations between NAFLD and the level of IL-1β, IL-6, IL-8 и TNF-α, the existence of the authentic connection of cytokines with the markers that define the violation of carbohydrate, lipid exchange, as well as the functional condition of liver. In contrast to NAFLD, comparing it to the patients without NAFLD, we found out the high readiness of cells for apoptosis, defined the activity of T-helpers of type 1, activity of the acute and chronic inflammatory process, and also more symptoms of immunotoxicosis, that is confirmed by more high level of pathogenic CIC of medium and small size. We showed that adiponectin has protector specifics of the NAFLD development among the patients with T2D, because with the combination of both of this diseases patients define lower level of adiponectin against the backdrop of negative connections of adiponectin with the index of HOMA-ІR, level of triglycerides, BMI and the continuance of diabetes. We defined the aggressive role of acyl-ghrelin among type T2D patients in the progression of NAFLD. This is confirmed by a higher level of acyl-ghrelin among the patients with the T2D and NAFLD; the existence of associations between acyl-ghrelin and the existence of NAFLD, regardless of the level of ALT, TG, AST and НОМА-IR, as well as good operational characteristics of the diagnostic model of predicting NAFLD and the determination of acyl-ghrelin strength. We created the algorithm of definition of patients of high risk of development of the complicated course of T2D on the basis of the created predicting model of speedy progression of fibrosis among the patients with T2D with the NAFLD. Final clinical model includes six prognostic variables: triglycerides level, alkaline phosphatase, insulin, IL-6, TNF-α and adiponectin. We created an integrated system of medical help to the patients with T2D and the associated NAFLD. The main components of this system are a patient with T2D and the risk factors of NAFLD development and the health care system with the strict definition of organizational technologies and multidisciplinary approach to the treatment and diagnostic process. The main innovational elements of this system are interdisciplinary coordination in the formation of the patients with T2D route between the institutions of different levels, interdisciplinary package of solutions with the prognosis and prevention of fibrosis in NAFLD, unified electronic medical documentation for monitoring patients, involving society in the preventive process in patients with T2D. We demonstrated that the complex therapy of T2D and NAFLD leads to decrease of clinical symptoms of the disease, improvement of carbohydrate, lipid and immunological status of patients, it also slows down the progression of the disease.

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