Pathogenetic and clinical rationale for syntropic pathology based on metabolic syndrome, coronary heart disease and type 2 diabetes mellitus
Authors: Chmyr N.V. , Dutka R. , Dronyk I. , Abrahamovych Kh. , Didenko O. , Fedechko M. , Drobinsʹka N. , Leont'yeva Z. 
Published: February 2024

Topicality. Metabolic syndrome (MS), type 2 diabetes mellitus (DM), and coronary artery disease (CAD) are global health problems. Cardiovascular diseases (CVD) are found in 34.8% of people with type 2 diabetes and MS. According to a meta-analysis of 102 prospective studies, it was found that the presence of diabetes mellitus doubles the risk of cardiovascular events against the background of metabolic syndrome [1]. According to WHO data, 39% of the population over 18 years of age is overweight or obese, which causes the recognition of this condition as a pandemic, which is directly associated with CАD and type 2 diabetes mellitus. In our opinion, the priority direction is the study of the relationship of the pathogenetic links of the investigated nosologies, which, in this case, is the basis of this syntropic pathology. In order to confirm their pathogenetic relationship, we studied the peculiarities of the lipid spectrum and hormonal metabolism in patients with CAD and type 2 diabetes mellitus on the basis of MS.The aim of the study: to investigate the pathogenetic and clinical features of the development of syntropic pathology on the example of such complications of metabolic syndrome as coronary heart disease (CHD) and type 2 diabetes.Material and methods. 110 patients (81 women, 29 men) with type 2 diabetes mellitus on the basis of metabolic syndrome with and without coronary artery disease were studied and divided into two groups (experimental and comparison group), comparable in age and gender. The control group included 20 healthy persons of appropriate age and gender. The research group (n = 75) included patients with type 2 diabetes mellitus on the basis of metabolic syndrome with coronary artery disease (women – 51 (68%), men – 24 (32%)). The comparison group included 35 patients with type 2 diabetes mellitus on the basis of MS without coronary artery disease (women – 30 (85.71%), men – 5 (14.29%)).Research design. At the first stage of the study, patients underwent a general clinical examination with verification of type 2 diabetes mellitus on the basis of metabolic syndrome and their distribution, depending on the presence or absence of coronary artery disease, into the defined 2 main clinical groups: experimental and comparison groups. Comprehensive examination included: collection of complaints and anamnesis, clinical examination, determination of anthropometric parameters, measurement of blood pressure; determination of the level of blood glucose, glycosylated hemoglobin in the blood serum. In addition, studies of the lipid spectrum, determination of the level of thyroid-stimulating hormone, prolactin, cortisol and free thyroxine were carried out. The obtained research results were compared with the corresponding data of the control group. To find out the state of lipid metabolism, indicators of total cholesterol (TCH), low-density lipoprotein cholesterol (LDL-CH), very low-density lipoprotein cholesterol (VLDL-CH), high-density lipoprotein cholesterol (HDL-CH), triglycerides (TG), atherogenicity coefficient were determined. The content of cortisol, prolactin, free thyroxine, thyroid-stimulating hormone was studied in all patients. Statistical processing of research results was carried out after creating a database in Microsoft Excel. Shapiro-Wilk and Kolmogorov-Smirnov criteria were used to determine the normality of the distribution of indicators. When the distribution did not conform to the law of normality (it turned out to be non-Gaussian), the statistical characteristics are presented in the form of "median [lower; upper quartile]". The differences between indicators were significant at p < 0.05.Research results. In patients of both groups the average values of cortisol exceeded the values of the control group by 52.47% and 38.79% (р1= Р6-0=0.000001, р2= Р3-0=0.0001), while - in the comparison group - by 14.28% less than in the experimental group (р=0.03). The women of the experimental group had a significantly higher, by 31.64%, level of prolactin than the patients of the comparison group, however, in women of both groups, the level of prolactin was 58.8% and 39.71% reliably (P6-0=0.008, P3 -0=0.04) higher than the control group (in contrast to the prolactin level in men). The concentration of TSH in patients of the experimental group did not significantly exceed the corresponding value in patients of the comparison group and individuals of the control group (p > 0.05). The level of total cholesterol in the experimental group exceeded the indicator of the comparison group by 13.79% (Р 6-3=0.0005) and by 23.93% (Р 6-0=0.000000002) of the control group, and, the level of total cholesterol in the comparison group was 11.76% (Р 3-0=0.001) higher than the level of the control group. The values of triglycerides in the experimental group exceeded, by 26.28%, the average values of triglycerides in individuals of the comparison group (P6-3=0.003), at the same time, the values of triglycerides of both groups were reliable (P3-0=0.000095 and P6-0<0.01) exceeded the level of triglycerides in the control group - by 72.76% and 63.04%. The values of VLDL in the experimental group exceeded the average values of the comparison group by 24.29% (Р6-3=0.02) and the values of the control group by 72.14% (Р6-0<0.01). The level of LDL in subjects of the experimental group was significantly higher (P6-0=0.000001) than the level of LDL in the control group, in contrast to the subjects of the comparison group (P3-0=0.08). HDL values in the experimental group were 13.79% lower than in the comparison group and 43.68% lower than in the control group (P6-0=0.000006).Discussion. Patients with coronary artery disease and decompensated type 2 diabetes mellitus on the basis of metabolic syndrome have significantly higher average values of cortisol and prolactin (in women) compared to patients with type 2 diabetes mellitus on the basis of MS without coronary artery disease. At the same time, TSH does not exceed the indicators of control values. Since insulin regulates the secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and prolactin according to the feedback principle, the presence of both groups of decompensated type 2 diabetes mellitus in our patients is accompanied by pronounced hyperglycemia, which acts as a stimulator of prolactin secretion and causes transient functional changes of this hormone for correction and normalization of metabolic changes that occur at the same time, as protection in response. Decompensation of type 2 diabetes mellitus in patients with coronary artery disease due to metabolic syndrome is accompanied by a decrease in the level of insulin to normal values, which in turn is accompanied by a normalization of the level of TSH and confirms the close relationship between the studied hormones. An increase in the level of cortisol in patients with type 2 diabetes mellitus on the basis of metabolic syndrome can be justified as a response to the decompensation of type 2 diabetes mellitus, and normal values of TSH confirm the interdependence between these hormones. Violations of the lipid spectrum are nonspecific, with an increase in the presence of CAD and type 2 diabetes mellitus on the basis of metabolic syndrome: the levels of total cholesterol, triglycerides, and VLDL-CH in the experimental group exceeded the indicators of the comparison group, which indicates the interdependence of pro-atherosclerotic factors.Conclusion. Thus, the metabolic syndrome is an example of the development of syntropic pathology and is pathogenetically and clinically related to type 2 diabetes mellitus both with and without CAD, and this is the basis of its treatment and prevention.