Pylypenko L. Diagnostic value of the study of markers of endothelial dysfunction and proinflammatory chemokines in patients with diabetic retinopathy and type 2 diabetes

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0820U100258

Applicant for

Specialization

  • 222 - Медицина

17-09-2020

Specialized Academic Board

ДФ 08.601.004

State institution "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine"

Essay

The thesis is devoted to solution of actual problems of modern ophthalmology – increase of efficiency of diagnostics for diabetic retinopathy in diabetes type 2 by studying markers of endothelial adhesive dysfunction and proinflammatory chemokines IL-8, PAI-1 and VCAM-1. Special attention is paid to the development of diabetic retinopathy (DR) is a microangiopathy of retinal vessels in DM that in the terminal stage leads to a complete loss of vision (blindness) affects more than 1/3 of all patients with diabetes and is a major cause of vision loss among people of working age (IDF, international diabetes Federation, 2018). Among patients with DM type II about 20 years almost everyone (95 %) leads to significant ophthalmologic complications, which can lead to disability and blindness (IDF, 2018). First established the information content of the definition of markers of endothelial adhesive dysfunction and proinflammatory chemokines in the assessment of progress ETC on the background of metabolic syndrome in patients with obesity and type 2 diabetes and obesity, which was 72,7-76,5%, depending on the set of variables of the mathematical model with sufficient level of statistical significance (p=0,030, p=0.005). Patients with PD for the first time revealed a statistically significant negative correlation of circulating levels of IL-8 and age of patients (p=0.03), highly significant (p<0.001) inverse relationship between PAI-1 and age of patients, highly significant (p=0.001) linear negative correlation between the activity of PAI-1 and duration of type 2 diabetes from the time of its verification, significant (p=0.005) moderately negative correlation of the activity of PAI-1 and level HbA1С, significant (p=0.001) positive correlation of the activity of PAI-1 and IL-8, a negative correlation between VCAM-1 and IL-8 (p=0,010), and the inverse linear dependence of the concentration of fibrinogen and activity of PAI-1 (p=0.005) and video – with the content of VCAM-1 (p=0.01). Updated scientific data on the risk factors for progression of DR that are for non-proliferative stage (NPDR) reliable modificacin the influence of patient age (over 60 years) (p=0,035), duration of diabetes (>10 years) (p=0.001) and the appointment of insulin (p<0.001) to the level of VCAM-1; for preproliferative stage of DR reliable modificacin influence the degree of compensation of carbohydrate metabolism in the content of triglycerides (p=0.018), and proliferative diabetic retinopathy (PDR) reliable modificacin influence the degree of compensation of carbohydrate metabolism (p<0.01) and type of diabetes treatment (insulin therapy) – the level of cholesterol low-density lipoproteins (LDL cholesterol) (p<0.001); age of patients (p<0.01), the level of compensation of carbohydrate metabolism (p=0.001) and type of hypoglycemic therapy (insulin therapy) (p<0.001) on the concentration of fibrinogen in the blood. Augmented scientific data VADT studies regarding the role of fibrinogen in the progression of DR on the basis of the regression analysis revealed a significant (p=0.03) positive linear correlation of fibrinogen levels with disease duration in patients with PD, especially during the first 10 years from verification of type 2 diabetes. Practical significance of the obtained results. Using regression and discriminant analyses of the proposed mathematical models for estimating the risk of DR in patients with type 2 diabetes with metabolic syndrome. Determined to be the most significant determination of the content of VCAM-1 in the blood NPDR and activity of PAI-1 with antitrombozitarnae therapy at all stages of PD. The application of mathematical models for assessing progression of PD including determination of blood circulating IL-8, the content of VCAM-1 activity and PAI-1 allows to predict the stabilization of the development of PD in 2/3 of cases (77,4 % of them in 73,52 % of the cases at stage I, and OTHERS at 82.4 % of cases in stage II, ETC.). Developed recommendations for assessing the risk of progression of DR in patients with type 2 diabetes and metabolic syndrome by determination of the content of circulating IL-8 regardless of the stage of PD, the concentration of fibrinogen in the blood when the da based on the age of patients, duration of type 2 diabetes mellitus, the degree of decompensation of carbohydrate metabolism and type of hypoglycemic therapy, the activity of PAI-1 adjusted for patient age (60 years), duration of diabetes (10 years), with subcompensation of carbohydrate metabolism, as well as the content of VCAM-1 on NPK given the age of the patients (over 60 years), duration of diabetes (>10 years) and the fact that the use of insulin therapy in the treatment of type 2 diabetes. It is important to further increase the effectiveness of the diagnosis of diabetic retinopathy in type 2 diabetes by studying the markers of endothelial adhesive dysfunction and proinflammatory chemokines IL-8, PAI-1 and VCAM-1.

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