OFFICIAL JOURNAL OF THE SCIENTIFIC SOCIETY OF
ANATOMISTS, HISTOLOGISTS, EMBRYOLOGISTS AND
TOPOGRAPHIC ANATOMISTS OF UKRAINE
ВІСНИК МОРФОЛОГІЇ
REPORTS OF MORPHOLOGY
DOI: 10.31393
ISSN 1818-1295
eISSN 2616-6194
Vol. 26, №3, 2020
Scientific peer-reviewed journal in the fields of normal and pathological anatomy, histology, cytology
and embryology, topographical anatomy and operative surgery, biomedical anthropology, ecology,
molecular biology, biology of development
Published since 1993
Periodicity: 4 times a year
Vinnytsya 2020
ORIGINAL ARTICLES
ВIСНИК МОРФОЛОГIЇ - REPORTS OF MORPHOLOGY
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ORIGINAL ARTICLES
CONTENT
Antoniuk Ya.O., Pashkova Iu.P., Gumeniuk A.F., Sakovych O.O., Zhebel V.M. Features of
hemodynamics in the comorbid course of essential hypertension and type 2 diabetes in men, residents of
Podillia, carriers of polymorphic variants of the brain natriuretic peptide gene..................................................... 5
Kryvoviaz Yu.O., Vernigorodskiy V.S., Dzevulska І.V., Shevchuk Yu.G., Zhuchenko P.S. Features
of the frequency of angio-, retino- and neuropathy, general clinical and anthropometric parameters in
patients with type 1 diabetes with different levels of albumin in the urine depending on the level of cystatin C ..... 14
Hruzevskiy O.A., Minukhin V.V. The vaginal bacterial dysbiosis severity predicting model according
to the normobiota index .................................................................................................................................... 24
Mateshuk-Vatseba L.R., Pidvalna U.Ye., Bekesevych A.M. Morphometric study of angioarchitectonic
under the effect of opioid (experimental study) .................................................................................................. 31
Prokopenko O.S., Beliaiev E.V., Dmitriev M.O., Cherkasova O.V., Skoruk R.V. Features of
cephalometric parameters, which usually do not change during surgery and orthodontic interventions,
in Ukrainian young men and women with orthognathic occlusion and different types and profiles of the
face according to Schwarz A.M. ....................................................................................................................... 37
Sotnikova-Meleshkina Zh.V., Redka I.V., Mikhalchuk O.Ya. The state of vegetative regulatory systems
of pupils with different academic performance ................................................................................................... 46
Ohinska N.V., Nebesna Z.M., Getmanyuk I.B. Micro- and submicroscopic changes of the cerebellar
cortex 21 days after modeling the burn ............................................................................................................. 52
Lytvynenko M.V., Gargin V.V. Morphometric peculiarities of the cervix uteri in immunodeficiency states...... 58
Sukhodolia A.I., Hnatjuk M.S., Krenyov K.Yu., Kolomiiets O.V. Morphometric evaluation of features
of remodelling of the venous bad of the limbs at experimental trophic ulcer and its correction .......................... 64
Sirman Ya.V., Savytskyi I.V., Preys N.I. Changes in the asymmetric dimethylarginine and
endothelial nitric oxide synthase levels in pathogenesis of experimental diabetic retinopathy .......................... 69
REPORTS OF MORPHOLOGY
Official Journal of the Scientific Society of Anatomists,
Histologists, Embryologists and Topographic Anatomists
of Ukraine
Features of hemodynamics in the comorbid course of essential
hypertension and type 2 diabetes in men, residents of Podillia,
carriers of polymorphic variants of the brain natriuretic peptide
gene
Antoniuk Ya.O., Pashkova Iu.P., Gumeniuk A.F., Sakovych O.O., Zhebel V.M.
National Pirogov Memorial Medical University, Vinnytsia, Ukraine
Essential hypertension (EH) and type 2 diabetes (T2D) are important risk factors for the
development of chronic heart failure (CHF). The early detection of CHF, especially under
comorbidity, remains a challenge. To solve it in today's conditions are used not only
instrumental diagnostic methods (Echo-CG), but also the assessment of plasma levels
of biomarker - brain natriuretic peptide (BNP), the expression of which is determined by
the corresponding gene (locus T-381C) and may depend on its structural organization. It
is proved that deregulation of the natriuretic peptide system (NP) is an important factor in
the initiation and progression of myocardial dysfunction and energy imbalance, but the
role of genetic preconditions for these disorders, including the peculiarities of polymorphic
variants of the most physiologically significant gene is still not enough clear. The aim of
the work was to investigate the presence of associations between indicators of systemic
and intracardiac hemodynamic and the carrier of polymorphic variants of the BNP gene
(T-381C) in men, residents of Podillia with the comorbid course of EH 2 and type 2
diabetes mellitus. We examined 132 middle-age men: 62 patients with EH 2 and chronic
heart failure (CHF) 0-I functional classes (FC) according to NYHA Classification and 70
- with EH 2 combined with T2D and CHF FC I-II. Patients with EH 2 included in the first
group and patients with EH 2 and T2D included in the second group of comparison.
Parameters of intracardiac hemodynamics were determined on the basis of pulsed
Doppler echocardiography. The genomic DNA of the BNP gene (T-381C) for the
determination of its alleles was isolated by PCR. The mathematical processing was
performed using the standard statistical package Statistica 10. We calculated the primary
statistical indicators, identified differences between groups on statistical signs, performed
correlation and discriminant analysis. The calculation of the relative risk with a 95%
confidence interval was performed using an online calculator (https://medstatistic.ru/
calculators/calcrisk.html). Among men living in Podillya with EH, both in the presence
and absence of diabetes mellitus 2, the T381C genotype of the BNP gene (p>0.05)
dominates. In the group of comorbid patients diastolic dysfunction of the left ventricle
(DD LV) was diagnosed in 90% of people (n=63), while in the isolated course of EH it was
found only in 43.55% (n=28). Although among homozygotes T381T BNP gene its symptoms
were 100% (n=24), and among carriers of the C allele - in 84.78% (n=39) of patients.
Carriers of the T381T genotype of the BNP gene dominated among persons with DD
grade II: 41.66% against 10.87% of carriers of the C allele (p<0.05), while among persons
with DD LV grade I there were more carriers of the C allele. Homozygous T381T genotype
with EH 2 and T2D had a higher level of pulse blood pressure (p<0,01), a higher probability
of developing eccentric left ventricular hypertrophy (p?0.05) and more pronounced diastolic
changes in the myocardium, as compared with carriers of the C allele and can be
allocated to the priority group of observation for the organization of targeted measures
aimed at preventing the development and progression of CHF.
Keywords: essential hypertension, type 2 diabetes, the brain natriuretic peptide gene
polymorphism, diastolic dysfunction.
ARTICLE INFO
Received: 18 June, 2020
Accepted: 21 July, 2020
UDC: 616.12-008.331.1/.46:616.379-
008.64:577.17:616-07-037
CORRESPONDING AUTHOR
e-mail: doktorafp@gmail.com
Gumeniuk A.F.
©
2020 National Pirogov Memorial Medical University, Vinnytsya
DOI: 10.31393/morphology-journal-2020-26(3)-01
Reports of Morphology, Vol. 26, №3, Pages 5-13
ISSN 1818-1295 eISSN 2616-6194
journal homepage:
https://morphology-journal.com
5
6
ISSN 1818-1295 eISSN 2616-6194 Reports of Morphology
Features of hemodynamics in the comorbid course of essential hypertension and type 2 diabetes in men, ...
Introduction
The combination of essential hypertension (EG) and
type 2 diabetes (T2D) as an additional factor of specific
adverse effects on the myocardium several times increases
the risk of cardiovascular complications due to the mutually
aggravating course of the disease and damage to common
target organs, including blood vessels and heart [13, 22,
24]. The inevitable end and the leading cause of death, as
in almost all cardiovascular diseases and T2D is the
development of chronic heart failure (CHF), the course of
which in comorbid patients is more severe and
characterized by a worse prognosis [12, 13, 16, 23].
In order to improve the individual strategy for the
prevention of CHF, especially in the comorbid course of EG
and T2D, there is an urgent need to use effective diagnostic
biomarkers of myocardial dysfunction at the stage of
reverse changes [33, 36]. Natriuretic peptides (NP) are
considered to be important markers, as well as biological
properties of direct antagonists of RAAS activity and
regulators of heart structure and function [21]. Currently,
the assessment of the informativeness of brain natriuretic
peptide (BNP) remains relevant, the plasma level of which
may depend on hereditary, sexual, age characteristics of
patients and metabolic changes in T2D [5, 10, 15, 32]. It is
known that the genotype is an important determinant of
BNP levels in the general community and explains some
variability in its plasma concentration [8, 11, 17]. That is
why there is a need to clarify the diagnostic significance of
allelic polymorphism of the BNP gene (locus T-381C-
SNPrs 198389) in left ventricular hypertrophy (LVH) and the
detection of early signs of CHF. This clarification seems
especially important in patients with T2D, because it is
proved that the violation of the regulation of the NP system
is a significant factor not only in the initiation and
progression of myocardial dysfunction, but also energy
imbalance [6, 33, 39].
The growing number of genetic and epidemiological
studies in recent years suggests that BNP involved in
cardiac stress is inversely associated with risk factors for
diabetes - with metabolic syndrome and insulin resistance,
but the expected association remains unclear [3, 7, 19].
Because metabolic processes, in turn, are closely linked
to the development of cardiovascular disease, interest in
the study of humoral agents that combine them has not
abated. That is why the role of BNP in the development of
remodeling and myocardial dysfunction, as well as the
genetic polymorphism of the gene, which may cause its
regulation, requires further evaluation under the conditions
of comorbidity of EG and T2D.
Studies conducted in this area in Ukraine are few. In
previous works, employees of the Department of Internal
Medicine of the Medical Faculty №2 National Pirogov
Memorial Medical University, Vinnytsia evaluated the
features of the structural and functional state of the
myocardium in carrying different variants of the BNP gene
in men, residents of Podillya in the isolated course of EG II
with different stages of CHF, but patients with T2D were not
included in the study [2, 25, 26, 27].
Continuing research to improve understanding of
pathogenetic mechanisms as a possible individual basis
for the development of CHF, taking into account genetic,
sex and population differences in the combined course of
EG and T2D may complement existing data and provide
new perspectives for early detection, timely and rational
treatment of these comorbid patients.
Purpose of study: to investigate the presence of
associations between indicators of systemic and
intracardiac hemodynamics and the carrier of polymorphic
variants of the BNP gene (T-381C) in men, residents of
Podillya with the comorbid course of EG II and T2D.
Materials and methods
The study was approved by the local ethics
commission, as well as the informed consent of all patients.
Surveyed 132 middle-aged men living in the Podillya region
of Ukraine in the third generation, at a distance of more
than 5 km from each other and which are not relatives. A
comprehensive clinical-anamnestic, anthropometric and
laboratory-instrumental examination was performed, on the
basis of which the diagnosis of EG II and CHF was
established in accordance with the recommendations of
the European and Ukrainian Association of Cardiologists
for the diagnosis and treatment of hypertension and CHF
[29, 31, 37].
Verification of the diagnosis of T2D was performed
according to the WHO criteria and according to the Order of
the Ministry of Health of Ukraine dated 21.12.2012 №1118
[9, 34]. The parameters of intracardiac hemodynamics were
determined on the basis of echocardiography. The criterion
of LVH for men was considered to be LV weight/height
2.7
>
50 g/m
2.7
according to the recommendations of the European
Association of Cardiologists for the diagnosis and treatment
of hypertension (2018) [37]. Diastolic LV function was
assessed according to current guidelines using pulsed
Doppler echocardiography [18]. Exclusion criteria were:
symptomatic hypertension, severe CHF (III-IV FC according
to NYHA) with reduced left ventricle emission fraction (<40%),
T1D, T2D decompensation, insulin therapy, diabetic
nephropathy 4-5 degree, chronic kidney disease of non-
diabetic origin, liver failure, chronic obstructive pulmonary
disease and bronchial asthma, acquired heart disease,
tumors, diseases of the blood system, concomitant
inflammatory and other endocrine diseases, except T2D.
Patients were divided into 2 groups. 62 individuals with
EG II and CHF 0-I FC according to NYHA were included in
the first, and 70 men with EG II in combination with T2D
and CHF I-II FC - in the second comparison group. The
genomic DNA of the BNP gene for the determination of
alleles of the polymorphic region (T-381C) was isolated by
Vol. 26, №3, Page 5-13
Antoniuk Ya.O., Pashkova Iu.P., Gumeniuk A.F., Sakovych O.O., Zhebel V.M.
7
PCR in collaboration with the Research Institute of Genetic
and Immunological Basis of Pathology and Pharmaco-
genetics of the Ukrainian Medical Dental Academy, Poltava
(Head of Laboratory - Doctor of Medicine, Professor
I.P.Kaidashev).
Mathematical processing of the results was performed
using the standard statistical package Statistica 10. Primary
statistical indicators were calculated, differences between
groups on statistical features were revealed, correlation
and discriminant analysis was performed. Relative risk
(RR) with a 95% confidence interval is calculated using an
online calculator (https://medstatistic.ru/calculators/
calcrisk.html).
Results
The frequency distribution of polymorphic genes in the
population was checked in accordance with Hardy-
Weinberg equilibrium law. Analysis of the frequency
distribution of genotypes of the BNP gene revealed the
dominance of the T381C variant (p<0.05) in both
comparison groups in the absence of a significant difference
between the number of carriers of individual polymorphic
variants in each group. For greater accuracy of comparative
analysis due to the small number of individuals -
homozygotes C381C they are combined with carriers of
the genotype T381C to one common group - carriers of the
C allele of the BNP gene (Fig. 1). In order to identify hereditary
preconditions for myocardial remodeling and dysfunction
in men with EG II in the presence of comorbid T2D, the
parameters of systemic hemodynamics and structural and
functional parameters of the myocardium in comparison
groups depending on the structural organization of the BNP
gene were determined (Table 1).
The Kendall rank correlation method was used to
investigate the possible relationship between the carrier
of polymorphic variants of the BNP gene and the values of
Fig. 1. Frequency of distribution of alleles of the BNP gene in
comparison groups among men living in Podillya (%). The difference
is significant (p<0.05) when compared with * - carriers of the C
allele within the group.
Table 1. Systemic hemodynamic parameters and structural and functional parameters of the myocardium in men with EG II, and EG II in
combination with T2D, carriers of different genotypes of the BNP gene, (M±m).
Notes: * - difference of indicators is statistically significant at (р<0.05); # - difference of indicators is statistically significant at (р<0.01).
Indicator
1. Patients
with EG II,
homozygotes
T381T (n=22)
2. Patients with
EG II, carriers
of the C allele
(n=40)
3. Patients with
EG II and T2D,
homozygotes
T381T (n=24)
4. Patients with
EG II and T2D,
carriers of the
C allele (n=46)
р
SBP, mm Hg 159.80±1.11 141.60±2.05 173.96±2.32 166.48±1.80 р
2-1
*; р
3-1
#; р
4-2
#; р
4-3
*
DBP, mm Hg 91.25±1.39 84.60±1.06 103.25±1.37 100.46±0.79 р
2-1
*; р
3-1
*; р
4-2
#; р
4-3
*
Pulse pressure, mm Hg 68.55±1.23 57.00±1.99 70.71±1.15 66.02±1.29 р
2-1
*; р
3-1
*; р
4-2
#; р
4-3
*
Heart rate, for 1 min. 78.16±0.12 74.37±1.43 83.00±2.74 78.43±1.82 р
3-1
*; р
4-3
*
Left ventricular posterior wall thickness, cm 1.32±0.02 1.18±0.02 1.36±0.04 1.17±0.03 р
2-1
*; р
4-3
*
Interventricular septal wall thickness, cm 1.36±0.03 1.22±0.02 1.33±0.03 1.26±0.04 р
2-1
*; р
4-2
#
Relative wall thickness, c.u. 0.54±0.03 0.51±0.01 0.51±0.03 0.52±0.02 р
3-1
*; р
4-2
*
LVMI, g/m
2.7
62.35±2.81 60.89±2.32 71.41±3.06 66.22±1.92 р
3-1
*; р
4-2
#; р
4-3
*
End diastolic volume index, mL/m
2
61.07±1.67 53.20±0.92 56.29±2.65 55.52±1.97 р
2-1
*; р
3-1
*; р
4-2
#
End systolic volume index, mL/m
2
26.28±1.26 21.14±0.80 21.71±1.61 21.36±1.31 р
2-1
*; р
4-2
*
Emission fraction, % 60.29±1.24 62.06±1.83 58.34±1.38 62.39±1.43 р
4-3
*
Left atrium, cm 3.82±0.10 3.58±0.08 4.00±0.05 3.80±0.08 р
2-1
*; р
4-2
#; р
4-3
*
Е/А, c.u. 0.89±0.07 0.83±0.06 1.09±0.13 0.73±0.05 р
3-1
*; р
4-2
*; р
4-3
*
E/Е', c.u. 7.77±0.38 6.25±0.24 10.13±0.50 7.69±0.23 р
2-1
#; р
3-1
#; р
4-2
#; р
4-3
#
DT, ms 249.02±3.43 254.07±4.27 194.79±6.37 255.07±5.12 р
3-1
#; р
4-3
#
IVRT, ms 95.35±2.09 91.46±2.14 109.15±2.82 119.11±2.23 р
2-1
*; р
3-1
*; р
4-2
#; р
4-3
#
individual indicators of systemic and intracardiac
hemodynamics. In men with a comorbid course of EG II
and T2D, the presence of a correlation between the carrier
of polymorphic genotypes of the BNP gene and the level of
DBP (=-0.53, p<0.05), interventricular septal wall thickness
indicators (=0.17, p<0.05), size of left atrium (=0.19,
p<0.05), LVMI (=0.18, p<0.05), E/A (=-0.42, p<0.05), DT
(=0.62, p<0.01), IVRT (=0.41, p<0.01), E/E' (=-0.60,
p<0.01) was found. The obtained data indicate that the
carrier of different variants of the BNP gene is to some
extent associated with indicators that characterize systemic
hemodynamics, the degree of myocardial remodeling and
the severity of LV DD.
Analysis of systemic hemodynamic parameters (Table 1)
showed that the level of pulse blood pressure was higher
in T381T homozygotes than in carriers of the 381C allele of
the BNP gene: 70.71±1.15 mm Hg against 66.02±1.29 mm
Hg (p<0.05). In addition, the mean values of systolic blood
pressure (SBP), diastolic blood pressure (DBP) and pulse
pressure among carriers of the T381T genotype were
higher in the group of comorbid patients (p<0.05, p<0.01).
Among men with EG II and T2D, carriers of the T381T
genotype had higher values of left ventricular posterior wall
thickness, left atrium, LVMI, and E/A and