Arterial hypertension (AH) with concomitant type 2 diabetes mellitus (T2DM) is a common and serious medical and social problem in the world today. [1, P. 249-258]. They have the common pathogenetic mechanisms and they are the components of the metabolic syndrome. [2, P. 1595-1607]. Determination of the mechanisms of development of T2DM in patients with AH remains one of the topical problems of modern medicine, as the comorbidity of these pathologies which potentiates the risk of cardiovascular accidents [3, P. 963-975].
In recent decades, actively discussed the role of adipose tissue hormones in the progression of metabolic disorders in AH and T2DM [4, P. 242-248]. It is established that adipokines are involved in glucose metabolism and in the progression of insulin resistance, which underlies T2DM. One of these adipokines is of omentin [5, P. 143-148]. Still not fully elucidated all the effects, properties and mechanisms of action of this adipokine in patients with AH and T2DM. Therefore, it is important to study the influence of omentin cardiohemodynamics on progression and metabolic disorders in these patients.
The aim was to improve the diagnosis of comorbid pathology of AH and T2DM based on the study of the omentin influence on cardiohemodynamics and metabolic disorders.
Materials and methods. The study included 75 patients with AH of II stage and 2nd degree (43 men and 32 women). The average age of patients was 54.7±5.4 years. The patients were divided into groups: group 1 (p=38) are the patients with AH without T2DM; Group 2 (p = 37) are the patients with combined AH and T2DM progression. Control group (p=20) was the most comparable by age and gender for the examined patients.
Diagnosis of hypertension was done according to the recommendations of the European society of hypertension and European society of cardiology (ESH/ESC, 2013) and the Ukrainian Association of cardiology for the prevention and treatment of hypertension (2013). The diagnosis of abdominal obesity (AO) were established on the basis of criteria adopted by the WHO (1997), carried out anthropometric measurements with calculation of body mass index (BMI) and the degree of obesity according to the IDF criteria (2015).
The diagnosis of T2DM was established in accordance with the General recommendations of the European Association for the study of diabetes (EASD, 2013).
The omentin level was determined by enzyme immunoassay with sets of reagents «BioVendor» (Czech Republic). The contents of tumor necrosis factor — alpha (TNF — α) and C — reactive protein (CRP) were measured by enzyme immunoassay with sets of reagents «DRG» (USA).
The study of lipid metabolism: total cholesterol (TC) in serum, high density lipoproteins (HDL), triglycerides (TG) were determined by enzymatic method using colorimetric sets «Human» (Germany). The cholesterol content in the low-density lipoprotein (LDL) determined by the formula Friedewald W.T .: LDL (mmol / L) = TC — (HDL + TG / 2.22).
The level of glycosylated hemoglobin (HbA1c) in whole blood was performed using test systems company «Reagent» (Ukraine). The index of insulin resistance (HOMA-IR) was calculated with the formula: HOMA-IR = insulin, mcU / mL * glucose, mmol / L / 22.5. When HOMA-IR>2.77 patients were considered insulin-resistant.
The concentration of fasting blood glucose and insulin in serum was determined by enzyme immunoassay using «DRG» kits (USA). To determine glucose tolerance an oral glucose tolerance test was performed.
Echocardiography was performed using a diagnostic system, «Phillips IU» (USA) according to standard methods in accordance with the recommendations of the American society of echocardiography (2015) sizing of the thickness of the interventricular septum , the rear wall of the left ventricle at the end of diastole, end-systolic size (ESS), end-diastolic size (EDS), fractional ejection (EF) of the left ventricle; estimated end-systolic volume (ESV), end-diastolic volume (EDV); end-diastolic volume (EDV); analysis of the diastolic function of the left ventricle (DFLV) was carried out during check-in transmitral diastolic flow, diastolic function of the right ventricle (DFRV) — when registering transtricuspid diastolic flow in the pulsed-wave Doppler mode; the mass of LV myocardium (MLVM) was calculated according to the formula of Devereux R. B. (1986), MLVM index was defined as the ratio of MLVM to the area of the surface of the body Brown D. W.(2000).
To evaluate structural-functional state of vessels underwent ultrasonography of common carotid arteries with measurement of the thickness of the intima-media complex of common carotid artery (IMC CCA) using ultrasound diagnostic system «Phillips IU», with a linear transducer with a frequency of at least 7 MHz in b-mode.
Statistical processing of the obtained results was carried out using the program package Statistica 8.0 using Student’s t-test.
Results. Analysis of anthropometric indices in the patients of both groups have established significant differences in BMI values, which in patients of the 1st group amounted to an average of 31,4±1,6 (p<0,05) in patients with combined course of AH and T2DM and 35,4±3,6 kg/m2(p<0,05) in comparison with the control group and patients, and isolated hypertension (table.1).
Table 1
Features of clinical and biochemical parameters of blood serum of examined patients (M± m)
| Figure,
unit of measure |
Control group (p=20) | AH (p=38) | AH with T2DM
(p=37) |
| BMI, kg/m2 | 24,6±1,6 | 31,4± 1,6* | 35,4± 3,6*/# |
| НОМА-IR | 1,6±1,2 | 4,2±1,6* | 5,6±2,4*/# |
| TG, mmol/l | 1,1±0,4 | 3,1±0,2 | 4,3±0,6*/# |
| Cholesterol,mmol/l | 4,5±0,6 | 6,4±0,6* | 7,2±0,4*/# |
| HDL cholesterol, mmol/l | 1,3±0,05 | 1,1±0,03 | 0,7±0,05*/ # |
| LDL, mmol/l | 3,2±0,23 | 3,38±0,5 | 4,2±0,6*/# |
| CRP, mg/l | 2,83±0,23 | 6,34±0,26 | 8,48±0,44*/# |
* – p<0,05 – significance of differences in comparison with the control group;
# – p<0,05 – significance of differences in comparison with patients with AH
Reduced sensitivity of tissues to insulin by the criterion of HOMA-IR was observed in both groups of patients with the highest values in patients of the 2nd group in comparison with controls and patients with AH (р<0,05) and correlated with BMI (r=0,44; р<0,001), TG level (r=0,46; р<0,001), indicating the development of systemic metabolic changes, in particular the development of insulin resistance, dyslipidemia and inflammation [6, P. 5-9].
Lipid disorders was significantly more prevalent in patients with combined course of the disease in comparison with patients of the 1st group (83,6% to 44,30%, respectively; р<0,05). In patients with combined course of AH and T2DM had a low level of HDL cholesterol and elevated levels of LDL cholesterol in comparison with the value of these indicators in the group of patients with AH (p<0,05). These data suggest that T2DM contributes to the progression of atherosclerotic vascular lesions.
In the study of IMC CCA, the average patients with hypertension amounted to 0,84±0,05 mm (p<0,05) in comparison with associated disease and the control group and in patients with AH and T2DM is 0,95±0,07 mm (p<0,05) and correlated with BMI (r =0,34; p <0,001), SBP (r =0,32; p <0,001), cholesterol (r =0,38; p <0,001), LDL cholesterol (r = 0,44; p <0,001), and the inverse relationship between IMC CCA and HDL cholesterol (r = 0,42; p <0,001) and HOMA-IR (r = 0,36; p <0,001). The marked increase in IMC CCA > 0,9 mm in patients with hypertension in 46,8% of cases and in 58,2% of cases in patients with combined course of the disease, due to the greater severity of atherosclerotic lesions is influenced by the index of insulin resistance (glucose and hyperinsulinemia) and indicates the influence of metabolic disorders on the progression of vascular remodeling.
Indicators IMC CCA was associated with age (p=0,034), BMI (p=0,046), waist (p=0,048) and HOMA-IR (p=0,046). In patients with combined course of 38.7% was observed atherosclerotic plaque with the degree of stenosis <10%, which requires monitoring of patients, as this may constitute a trigger factor for development of cardiovascular complications.
Myocardium hypertrophy of the left ventricle (LVH) was diagnosed in 67,5% of patients of the 2nd group and in 36.2% of patients of the 1st group in comparison with control (p<0,05). In patients with hypertension and type 2 diabetes was dominated by concentric hypertrophy of the left ventricle (65%), also characterized by the increase in the average values of LVM (p<0,05) and i (p<0,05) in comparison with patients with AH and control group (p<0,05).
The indicators of intracardiac hemodynamics in patients with arterial hypertension was characterized by decreased velocity of early and late diastolic LV filling (table.2). Thus, in the combined course of the disease, these figures were significantly reduced in comparison with the 1st group of patients and control (p<0,05). A similar trend was observed in the speed ratio of early and late diastolic filling (E/AL) of the left ventricle. Also the maximum values of the LV DAC (of 4,18 and 3,95 cm, respectively) and the CRA LV (of 5,16 and 5,56 cm) was observed in patients of the 2nd group in comparison with indicators of the 1st group and the control (p<0,05). The same trend noted in regard to CSR indices of the LV (and of 48,1 to 78,4 cm3 ) and EDV of the LV (135,24 and 144,2 cm3; p<0,05). In patients with combined flow was observed a significant increase in BCL in comparison with indicators of the 1st group (p<0,05), which suggests that more pronounced changes in diastole were observed in patients with combined course of AH and T2DM.
Table 2
Hemodynamic parameters in the surveyed groups of patients with AH and match over AH and T2DM
| Indicators | Control
p=20 |
AH
p=38 |
AH + T2DM
p=37 |
| SBP,mm Hg.St. | 124,6±4,6 | 156,9±3,4* | 184,7±4,8#/* |
| DBP,mm Hg.St. | 81,9±5,7 | 90,2±5,3* | 105,2±9,3#/* |
| Systole phase LA, cm | 2,71±0,09 | 2,82±0,10 | 3,65±0,07#/* |
| EDV, cm³ | 129,0±1,16 | 135,24±1,16 | 144,2±1,16 #/* |
| ESV cm³ | 47,4±0,3 | 48,1±0,4 | 78,4±0,6#/* |
| EDS, cm³ | 4,64±0,02 | 5,16±0,04* | 5,56±0,08*/# |
| ESS LV, сm | 4,14 ±0,04 | 4,18±0,04 | 3,95±0,02 |
| Stroke volume (SV), cm³ | 75,6±1,28 | 83,9±1,36 | 97,2±0,72#/* |
| Ejection fraction (EF),% | 64,4±0,84 | 66,8±0,74 | 56,7±0,46* |
| Index of LV myocardial mass, g/m² | 81,8±0,02 | 98,6±0,03 | 142,6±1,34#/* |
* – p<0,05 – significance of differences in comparison with the control group;
# – p<0,05 – significance of differences in comparison with patients with hypertension
Thus, when comorbid AH and T2DM observed structural, functional, and intraventricular hemodynamic changes that occur in the diastolic dysfunction of the myocardium due to impaired diastolic relaxation of the LV myocardium. The concentration level omentin serum showed a significant decrease in patients with combined pathology of 1.5 times in comparison with patients with hypertension (p<0,001).
There was a negative correlation relationship between the plasma content omentin and indicators SBP (r = -0,61; p <0,05), DBP (r = -0,68; p <0,001), left ventricular hypertrophy (r = -0,64 ; p <0.05), BMI (r = -0,36; p <0,05), TG levels (r = -0,44; p <0,001), CRP (r = -0.38; p < 0,001), TNF — α (r = -0,44; p <0,001) and the degree of severity of IMC CCA (r = -0,36; p <0,05). The positive correlation relationship between the level and content of omentin HDL cholesterol (r = 0,46; p <0,001). Positive correlation relationship between the level of omentin and content of HDL cholesterol (r = 0,46; р<0,001). An inverse relationship between the level of omentin and glucose (r=-0,34; р<0,05), HOMA-IR (r = -0,46; р<0,001), indicating the influence of omentin cardiohemodynamics on progression and metabolic disorders in patients with AH combined with T2DM and is an additional risk factor in the pathogenesis of these patients.
Conclusions:
1. For concomitant hypertension and type 2 diabetes is a common pathogenic relationship, such as insulin resistance, systemic inflammation and dyslipidemia, which are potentiated progression of atherosclerosis, violations of intracardiac hemodynamics and structural and functional changes in vessels and a myocardium.
2. It was proved that changes in the level of omentin closely associated with impaired carbohydrate and lipid metabolism in patients with hypertension and type 2 diabetes that contributes to atherosclerotic vascular lesions and greatly increases the risk of cardiovascular complications in these patients.
3. Corellation determined the relationship of carbohydrate and lipid metabolism in serum, which also contributes to progression of atherosclerosis and worsening of the disease in patients with comorbidity of AH and T2DM.
References:
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- Thakur V., Richards R., Reisin E. Obesity, hypertension and the heart /V.Thakur et al.// Am. J. Med. Sci.-2001.-Vol. 321.- Р. 242-248.
- 5Tan B.K., Adya R., Randeva H.S. Omentin: a novel link between inflammation, diabesity, and cardiovascular disease / B.K. Tan et al. //Trends Cardiovasc. Med.-2010.Vol.20 (5)-P.143-148.
- Protasov K.V. Atherogenic dyslipidemia in diabetes part 1: pathogenesis, clinical and prognostic significance of monitoring indicators of lipid metabolism/K. V. Protasov// Siberian medical journal.- 2012.Vol.112.- P. 5-9.[schema type=»book» name=»THE PECULIARITIES OF THE CARDIAC HEMODYNAMICS AND METABOLIC DISORDERS IN PATIENTS WITH THE ARTERIAL HYPERTENSION AND DIABETES MELLITUS TYPE 2 DEPENDING ON THE LEVEL OF ADIPOKINES» description=»In the article, additional common pathogenetic factors of progression, concomitant arterial hypertension and diabetes mellitus type 2. The influence of adipose tissue hormones, in particular omentin, the progression of cardiohemodynamic and metabolic disorders in patients with arterial hypertension combined with diabetes mellitus 2.» author=»L. Bobronnikova, Bilovol » publisher=»Басаранович Екатерина» pubdate=»2016-12-04″ edition=»euroasia-science_30_22.09.2016″ ebook=»yes» ]