DOI: http://dx.doi.org/10.20534/ELBLS-17-1-14-16
Bobronnikova Lesya Romanivna, The Head of Clinical Pharmacology Department of Kharkiv National Medical University, MD, Professor, Ukraine, Kharkiv
E-mail: [email protected] Bilovol Olexandr Mykolayovich, Academician of the National Academy of Medical Sciences (NAMS) of Ukraine, MD, Professor of Clinical Pharmacology Department
of Kharkiv National Medical University Al-Trawneh Olena Volodymyrivna, Postgraduate student of Clinical Pharmacology Department of Kharkiv National Medical University E-mail: [email protected]
The pathogenetic interrelation of metabolic disorders in patients with arterial hypertension and type 2 diabetes mellitus
Abstract: The article deals with the mechanisms of progression of metabolic disorders in patients with concomitant course of hypertension and diabetes mellitus type 2, the most important is the state of insulin resistance, carbohydrate metabolism disturbances, the development of atherogenic dyslipidemia and systemic inflammation in correlation with the imbalance of adipocytokines, which contributes to high risk cardiovascular. Keywords: arterial hypertension, diabetes mellitus type 2, metabolic disorders, insulin resistance.
Combined for arterial hypertension (AH) and diabe- tive peptides [9]. There is evidence that some substances
tes mellitus (DM) type 2, contribute in the early stages of synthesized by adipose tissue can impair insulin signal
development of target organ damage and, consequently, transduction and cause IR in early stages on the stage of
increases the risk of cardiovascular events [1; 2]. pre-diabetes [10].
The identification of insulin resistance (IR) effect on Aim. To stud the features of metabolic disorders in
the incidence of cardiovascular events development in patients with AH and DM type 2.
DM type 2. Materials and methods. The study involved 74 pa-
Studies of the last years established that high insulin tients with AH and DM type 2: the 1st group consisted
level in the blood serum can accelerate the development of 38 patients with AH, 2nd group — 36 patients with
of atherosclerotic processes [3; 4]. concomitant AH and DM type 2. The control group (n =
IR is considered not only as the main link in the de- 20) was the most comparable in age and sex to the patients
velopment of DM type 2 and its complications, but also surveyed. The average age of patients was 54,7 ± 4,5 years.
a component which participate in the pathogenesis of Clinical examination of patients included an analysis of
atherosclerosis, hypertension and other diseases [5; 6]. complaints, collection of medical anamnesis, physical
The evidence from epidemiological studies indicate monitoring and an evaluation ofanthropometric indicators.
that approximately 80-90% ofpatients with DM type 2 are Diagnosis of hypertension was performed accord-
overweight or obese. Thus, the presence of I degree obe- ing to the recommendations of the European Society of
sity is 2 times increase the risk of developing DM type 2, Hypertension and the European Society of Cardiology
II degree — 5 times, III degrees — more than 10 times. A (ESH/ESC, 2013), as well as Ukrainian Association of
particular role is played by fat distribution [7]. Established Cardiology on prevention and treatment of hypertension
that visceral fat accumulation is associated with impaired (2013). To study the anthropometric characteristics of
glucose tolerance and IR regardless of body weight [8]. the course ofAH and DM type 2, patients were grouped
Adipose tissue is an endocrine organ that is the site according to Body Mass Index (BMI). The diagnosis of
of synthesis of a large number of hormones and bioac- DM type 2 were carried out according to the criteria of
The pathogenetic interrelation of metabolic disorders in patients with arterial hypertension and type 2 diabetes mellitus
the International Diabetes Federation (IDF, 2015). The criteria for inclusion into study was subcompensated diabetes: Impaired fasting glycaemia (IFG) not exceeding 8.5 mmol/l, postprandial hyperglycemia not exceeding 11 mmol/l and HbAlc level not higher than 9%.
Lipid spectrum Indicators of blood serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein — (HDL), low-density lipoprotein (LDL) was determined by an enzymatic colorimetric method using sets «Human» (Germany).
Insulin levels in blood serum were determined by enzyme-linked immunosorbent assay ELISA, «DRG» sets, (USA). Assessment of insulin resistance level was performed using HOMA (homeostasis model assessment) — homeostasis model assessment to insulin resistance by calculating the index (HOMA-IR) by the formula: HOMA-IR = insulin mcU/ml, glucose, mmol/l/22.5. The concentration of glucose in fasting blood serum (FBS) was determined by glucose oxidation method, also was determined glucose tolerance.
The content of tumor necrosis factor-a (TNF-a) in the blood serum were determined by enzyme immunoassay using sets of «Protein contour» (St. Petersburg).
The content of C — reactive protein (CRP) was analyzed by using ELISA with «DRG» set of reagent (USA).
The statistical processing of the results the research carried out by means of the software package Statisti-ca — 6.0 using Student's t-test and nonparametric statistical methods.
Results and discussion. The analysis of the tropho-logical status identified characteristics for both groups. Patients with BMI in the range 18.5-24.9 kg/m2 (5 patients) identified in the group with progression of isolated AH. However, III degree of obesity (BMI exceed 40.0 kg/m2) was observed in two patients with AH and in 6 patients with concomitant AH and DM type 2. The predominant majority of patients with isolated and combined course of the disease (67.5% and 55.1%, respectively) had a BMI in the range 30-34,9 kg/m2. Thus, in patients with AH and BMI 30-34,9 kg/m2 prevail men (72.4%), and with a BMI 35-39,9 kg/m2 and more — women (74.6%).
Indicators of the lipid levels in patients with comor-bid hypertension and DM type 2, characterized by the progression of an atherogenic dyslipidemia. The triglyceride levels in blood serum of patients with AH and DM type 2 is 1.5 times (p<0,05) higher than in patients of the 1st group and 2.2 times higher- indicators of the control group (p<0,05). Reducing HDL levels in patients with
AH and DM type 2 was observed significantly more frequently than in the control group (55.2% and 23.5%, respectively; p <0.05). In patients with comorbidities BMI 30-34,9 kg/m 2 had lower HDL levels compared with the value of this indicator in the comparison group (p <0.05). Progression of lipid disorders in patients with concomitant course of the disease depending on BMI: maximum values of TC and TG were observed with BMI 35-40 kg/m 2 (p = 0.242, p = 0.052, respectively), and the concentration of HDL in blood serum had the lowest value.
The concomitant and DM type 2 caused to increase in the ratio of an atherogenic index (AI) in 2.3 times in comparison with the control and 1.2 times with the comparison group, indicating the progression of atherosclerotic lesions in blood vessels.
Analysis of the insulin resistance (IR) indicators in patients of both groups testified that the maximum values of HOMA-IR index, insulin and C-peptide were patients in the 2nd group in comparison with indicators of the 1st group and the control (p = 0.000; p = 0.008; p = 0.004, respectively), indicating that the progression of in hyperinsulinemia conditions associated with the presence of DM type 2.
HOMA-IR index exceeded the control indicators by 2.1 times in the group of patients with isolated course of disease and 2.4 times was significantly higher in patients with concomitant AH and DM type 2 (p = 0.004).
Identified statistically significant relationship between glucose levels (r=0,52; p=0.04), C-peptide (r=0,64; p=0.000l), BMI (r = 0,56; p = 0, 0052) and the level of TC (r=0,62; p=0.054) confirms the hypothesis that IR influence on the development of dyslipidemia and associated with inflammation in patients with concomitant AH and DM type 2.
Impaired glucose tolerance (IGT) in patients with AH was observed in 9.5% of cases (p<0.05), whereas patients of 2nd group in 96.7% (p<0.05). A significant increase of HbAlc observed in patients of 2nd group compared to control (p<0.05) confirms the negative impact of excess weight on carbohydrate metabolism and unsatisfactory compensation of carbohydrate metabolism, which increases the metabolic disorders and cause the atherosclerotic vascular lesion, patients of the 1st group 1 (7.6%) has been observed a significant increase in FBG levels compared to the control group (p<0.05), which is explained by the presence of abdominal obesity, because excess body weight is one of the cause for IR progression, the maximum value of this indicator has been reached in patients with concomitant AH and DM type 2 (p<0.05).
In both groups, there was observed a significant increase of TNF-a in blood serum comparatively to the control group (p <0.05). The largest increase in 2.5 times (p <0.001) was observed in concomitant course of AH and DM type 2.
CRP levels in blood serum exceed the reference values in both groups of surveyed patients (p <0.05). The greatest increase for CRP indicators (in 2.2 times) was observed in patients with comorbidity (p <0.05) and correlated with BMI (r = 0,43; p <0.001), FBG level (r = 0,48; p < 0.001) and TG levels (r = 0,37; p <0.04), index of HOMA-IR (r = 0,46; p <0.001).
Conclusion. It was found that the mechanisms of metabolic disorders in patients with concomitant AH and DM type 2, characterized by insulin resistance and progression of the development of atherogenic dyslip-idemia, an increase in markers of systemic inflammation are most pronounced in patients with overweight and obesity.
Thus, a comprehensive diagnosis ofAH and DM type 2, will contribute to the individualization of preventive and therapeutic measures, as well as the establishment of control for the progression of atherosclerosis and reduce cardiovascular risk.
References:
1. Inflammation in the pathophysiology of essential hypertension/F. Montecucco A., Pende A. Quercioli [et al.]//J. Nephrol. - 2011. - Vol. 24. - P. 23-34.
2. Shimamoto K. Metabolic syndrome/K. Shimamoto, T. Miura//Nippon Rinso. - 2015. -V. 67 (4). - P.771-776.
3. Yamawaki H. Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses/H. Yamawaki//Biol. Pharm. Bull. - 2011. - Vol. 34 (3). - P. 307-310.
4. Hackam D. G. The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension/Hackam D. G. et al.//Can. J. Cardiol. - 2014. - Vol. 26, - No 5. - P. 249-258.
5. Sarwar N., Gao P., Seshasai S. R., et al. Diabetes mellitus, fasting blood glucose concentration, and risk ofvascular disease: a collaborative meta-analysis of 102 prospective studies/N. Sarwar, P. Gao, S. R. Seshasai, et al.//Lan-cet. - 2016. - Vol. 375 (9733). - P. 2215-22.
6. Pereira M., Lunet N., Azevedo A., Barros H. Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries/M. Pereira et al.//J. Hypertens. - 2012. - Vol. 27. - P. 963-975.
7. Fonseca V. A. Defining and Characterizing the Progression of Type 2 Diabetes/V. A. Fonseca//Diabetes Care. -2009. - Vol. 32 (2). - P. 151-56.
8. Arror A. R. Insulin resistance and heart failure: molecular mechanisms/A. R. Arror//Heart Fail Clin. - 2012. -Vol. 8 (4). - P. 3133-3140.
9. Boudina S. Diabetic cardiomyopathy, causes and effects/S. Boudina//Rev. Endocr. Metab. Disord. - 2015. - No 11. - P. 31-39.
10. Zhou J. and Qin G. Adipocyte dysfunction and hypertension/J. Zhou and G. Qin//American Journal of Cardiovascular Diseas. - 2012. - Vol. 2. - P. 143-149.
DOI: http://dx.doi.org/10.20534/ELBLS-17-1-16-19
Lytvynets Liudmila Yaroslavivna, Doctor of Medicine, Professor, Departament of Pediatrics Ivano-Frankivsk National Medical University E-mail: [email protected]
Clinical significance of gene polymorphism of xenobiotic Detoxification in children with bronchial asthma
Abstract: The phenotypic peculiarities of bronchial asthma (BA) in 94 children from Ivano-Frankivsk region with different types of allelic gene polymorphism of the first phase of xenobiotic detoxification — mEPXHl have been investigated. The association between polymorphism of gene mEPXHl and susceptibility