EFFECT OF THE BODY WEIGHT INDEX ON THE INTENSITY OF METABOLIC DISORDERS IN ESSENTIAL HYPERTENSION PATIENTS ASSOCIATED WITH ISCHEMIC HEART DISEASE AND TYPE 2 DIABETES MELLITUS

Objective of the work is to study peculiarities of metabolic disorders in patients with essential hypertension stage I (EH stage I) associated with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM 2) depending on the body mass index (BMI). Material and methods. 45 patients with EH stage II associated with IHD, 52 patients with EH stage II associated with IHD and DM 2, 26 practically healthy individuals representative by the age and sex were included into the investigation. The indices of carbohydrate and lipid metabolism, oxidative homeostasis, the content of nitrogen monoxide (NO) final metabolites in the blood depending on BMI were investigated. Results. In patients with EH stage II associated with IHD and excessive body weight compared with the control a reliable increase of immunoreactive insulin (IRI) concentration and HOMA-IR index were determined. In case of obesity I a reliable increase of glucose concentration in plasma, IRI, HOMA-IR index, decreased concentration of high density lipoprotein (HDL) cholesterol and increased content of low density lipoprotein (LDL) cholesterol, increased concentration of Malone aldehyde (MA) in erythrocytes were determined compared with the control and patients with normal body weight. A direct interrelation of a moderate density between IRI content and body weight, reverse direct correlation of a moderate density between HDL cholesterol and body weight were determined. In patients with EH stage II associated with IHD and DB 2 and obesity I a reliable increase of total cholesterol concentration (42,54%), triacylglyceroles (42,5%), LDL cholesterol (14,5%), MA of erythrocytes (16,14%), decreased content of HDL cholesterol (18,0%), reduced glutathione (17,75%), normalization of catalase activity in comparison with the patients with normal body weight were found. A direct correlation was found between moderate density and IRI level and body weight, total cholesterol, HDL cholesterol, MA, catalase; between body weight and total cholesterol. Conclusions. In patients with EH stage II associated with IHD dependence of certain indices of metabolism and body mass index was determined. In the blood of patients with obesity I compared with those having excessive body weight, a reliable (p<0,05) increase of IRI concentration and HOMA-IR index, LDL cholesterol, decreased concentration of HDL cholesterol, increased content of MA in erythrocytes were found. More pronounced effect of increased body weight on metabolism was found in patients with EH stage II associated with IHD and DM 2.

Introduction. Arterial hypertension (АH) is the most spread cardio-vascular disease (CVD) in the world and Ukraine [1]. In recent years therapists have given great consideration to the issues of comorbidity and polymorbidity. AH is known to be most often associated with ischemic heart disease (IHD) among diseases of the cardio-vascular system [2]. The issue of comorbidity of AH and type 2 diabetes mellitus is especially serious problem, which is associated with much earlier development of damage of the target organs followed by cardio-vascular disasters [3,4]. In diagnostics and treatment of AH not only the level of arterial pressure should be considered, but availability of comorbid risk factors as well, since under their effect the total value of risk can increase substantially. Special attention is drawn to the problem of excessive body weight and obesity in the formation of cardiovascular risk [5].
Material and methods. 97 patients suffering from EH stage II associated with IHD (angina of effort I-II functional class) and moderate sub-compensated DM 2 were included into the study. Chronic heart failure was not higher than II functional class (NYHA ІІ). The age of patients was from 36 to 72 years. The control group included 26 practically healthy individuals representative by their age and sex.
Fasting glucose range in the blood serum was examined using the set of test-systems (BIO-LA-TEST, Erba Lachema, Czech Republic). Fasting insulin level in the blood was determined using the standard sets produced by Monobind Inc. (USA) by means of immune-enzyme analysis method.
The normal values of fasting insulin concentrations for men were those close to 25 mclU/mL, for women -to 23 Insulin resistance was verified in case of НОМА-IR value higher than 2,77 mclU/mL х mmol/L [6]. Lipid metabolism was examined by means of detection of the total cholesterol, high density lipoprotein (HDL) cholesterol, triacylglyceroles (TG) using diagnostic standard sets produced by Ltd. «Philicit-Diagnostics». Low density lipoprotein (LDL) cholesterol range was determined according to the formula suggested by W. Friedewald: LDL cholesterol = total cholesterol -HDL cholesterol -TG/2,2.
The state of LPO and antioxidant protection before and after treatment was evaluated by the levels of Malone aldehyde (МА) in the blood plasma and erythrocytes, the content of reduced glutathione (RG) in the blood plasma, glutathione peroxidase (GP), and catalase.
Endothelial function state was assessed by means of detection of NO production in the body according to the total level of its final metabolites (nitrites and nitrates) in the blood plasma.
The results of the study were statistically processed by means of detection of arithmetic mean values (М) and standard error (m). Distribution of normal samples was checked by Shapiro-Wilk criterion. Probability of changes in case of normal distribution in samples was determined by Student criterion, and in other cases Wilcoxon test was applied. The difference between samples was considered to be statistically reliable with р<0,05.
Results and discussion.
To study the role of the body weight in the development of metabolic disorders the examined two groups of patients suffering from EH with comorbid IHD and DM 2 were divided into two subgroups: the first one -with   (BMI 25,9 kg/m2) and the second one -with obesity I degree (BMI 30,9 kg/m2). Changes of metabolic indices in patients with EH stage II associated with IHD depending on BMI are presented in Table 1. Analyzing the results shown in the table we have determined a reliable increase of IRI concentration and HOMA-IR in patients with EH stage II associated with IHD from the first subgroup with BMI compared with that of the control. In patients from the second subgroup (obesity І) a reliable increase of glucose concentration in the blood plasma, IRI, HOMA-IR, were found compared with that of the control and those from the group with excessive body weight. Practically similar levels of hypercholesterolemia (Р<0,05) and triacylglycerolemia (Р<0,05) were found in the first and second subgroups of the examined patients compared with the control.
Increase of BMI influenced more substantially on the concentration of HDL cholesterol, LDL cholesterol, MA of erythrocytes. Patients from the second subgroup with obesity I developed reliable decrease of the concentration of HDL cholesterol and increased content of LDL cholesterol, increase of MA concentration in erythrocytes compared with that of the control and patients from the first subgroup with excessive body weight. The concentration of MA in the blood plasma, the content of RG, GP, catalase and concentration of NO final metabolites were practically similar reliably higher from that of the control in both subgroups of patients ( Table 1). The correlation analysis conducted in measuring anthropometric data, insulin resistance indices, carbohydrate and lipid metabolism, in patients with EH stage II associated with IHD has found direct interrelations of a moderate density between IRI content and body weight (r=0,34, р<0,05), total cholesterol (r=0,32, р<0,05), NO concen- Original research tration (r=0,43, р<0,05). A reverse correlation was found between a moderate density, HDL cholesterol range, and body weight (r=-0,37, р<0,05). Increased BMI produced more marked effect on metabolism of patients from the second group with EH stage II associated with IHD and DM 2 ( Table 2). Diabetes mellitus in patients from the second subgroup with obesity I was associated with reliable increase of total cholesterol concentration (42,54%), TG (42,5%), LDL cholesterol (14,5%), decreased content of HDL cholesterol (18,0%) compared with the patients from the first subgroup with excessive body weight. A reliable increase of erythrocyte MA concentration (18,5%) and in plasma (16,14%), decreased content of RG (17,75%), normalization of catalase activity were found compared with the patients with excessive body weight. Activity of GP and content of NO final metabolites were reliably higher than those of the control, but they did not differ from the indices of patients with excessive body weight. Carbohydrate metabolism disorders were more pronounced in patients from the second subgroup with obesity I. Direct correlation was determined between a moderate density, IRI range and body weight (r=0,35,р<0,05),total cholesterol (r=0,33,р<0,05),HDL cholesterol (r=0,32,р<0,05), MA (r=0,50,р<0,05),catalase (r=0,32,р<0,05); between body weight and total cholesterol (r=0,39, р<0,05).
Therefore, according to the data obtained for patients with EH stage II associated with IHD, develop insulin resistance (IR) increasing in case of obesity and DM 2 available. The concentration of free fatty acids in the blood is known to increase. Free fatty acids in the liver prevent insulin binding by hepatocytes disturbing metabolic insulin clearance promoting development of hyperinsulinemia. Moreover, free fatty acids disturb absorption and utilization of glucose by muscles promoting development of insulin resistance [7]. Insulin resistance of the muscular, adipose tissues, liver cells causes increased insulin secretion and glycemic index, which on the one hand is compensatory, and on the other hand is pathologic, since it promotes occurrence and development of metabolic, hemodynamic, organ disorders with the development of type 2 diabetes mellitus, IHD and other manifestations of atherosclerosis [8]. Insulin resistance available in patients with arterial hypertension with excessive body weight is stated by other authors as well [9].
Therefore, according to the data obtained for patients with EH stage II associated with IHD, develop insulin resistance (IR) increasing in case of obesity and DM 2 available. The concentration of free fatty acids in the blood is known to increase. Free fatty acids in the liver prevent insulin binding by hepatocytes disturbing metabolic insulin clearance promoting development of hyperinsulinemia. Moreover, free fatty acids disturb absorption and utilization of glucose by muscles promoting development of insulin resistance [7]. Insulin resistance of the muscular, adipose tissues, liver cells causes increased insulin secretion and glycemic index, which on the one hand is compensatory, and on the other hand is pathologic, since it promotes oc-currence and development of metabolic, hemodynamic, organ disorders with the development of type 2 diabetes mellitus, IHD and other manifestations of atherosclerosis [8]. Insulin resistance available in patients with arterial hypertension with excessive body weight is stated by other authors as well [9].
Increase of BMI and obesity is associated with reliable deterioration of lipid spectrum indices in the examined patients with EH stage II associated with IHD. It is more pronounced in case of DM 2 which is indicative of independent pro-atherogenic action of type 2 diabetes mellitus. A negative effect of obesity on the indices of lipidogram in patients with EH, DM 2 is suggested by other authors as well [10,11].
Carbohydrate and lipid metabolism disorders in the examined patients with EH stage II associated with IHD and DM 2 is intensified by lipid peroxide oxidation and exhaustion of the antioxidant protection system, which is more pronounced with DM 2 available. Excessive activation of free radical processes causes the whole cascade of negative reactions and pathologic processes underlying arterial hypertension, IHD, DM etc. [12].
Conclusions. In patients with EH stage II associated with IHD dependence of certain indices of metabolism and body mass index was determined. In the blood of patients with obesity I compared with those having excessive body weight, a reliable (p<0,05) increase of IRI concentration and HOMA-IR index, LDL cholesterol, decreased concentration of HDL cholesterol, increased content of MA in erythrocytes were found. More pronounced effect of increased body weight on metabolism was found in patients with EH stage II associated with IHD and DM 2.
Prospects of further studies: to determine efficacy of anti-hypertensive and metabolite-tropic therapy of patients with EH associated with IHD and DM 2 depending on BMI.