Значимость опросника WHOQOL-BREF и нейромаркера BNDF у больных сахарным диабетом 2 типа, находящихся на гемодиализе, в оценке степени ишемии головного мозга

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The importance of the questionnaire WHOQOL-BREF and
neuromarker BNDF in patients with type 2 diabetes
mellitus on hemodialysis in the assessment of the degree
of brain ischemia

Alisher KHOLIKOV

1

Republican Specialized Scientific and Practical Medical Center of Endocrinology named after

academician Ya.Kh. Turakulov of the Ministry of Health of the Republic of Uzbekistan.

ARTICLE INFO

ABSTRACT

Article history:

Received August 2024
Received in revised form

15 September 2024
Accepted 25 September 2024

Available online

15 October 2024

This study aims to evaluate the significance of the WHOQOL-

BREF questionnaire, a tool for assessing quality of life, and the

biomarker brain-derived neurotrophic factor (BDNF) in

patients with type 2 diabetes mellitus (T2DM) complicated by
chronic kidney disease (CKD) who are receiving hemodialysis. A

total of 90 patients with T2DM and stage III chronic renal

failure (CRF) undergoing programmed hemodialysis were

examined between January 1, 2019, and December 31, 2020.
These patients were divided into three groups based on the

severity of chronic cerebral ischemia (CCI). The results showed

that as the degree of CCI increased, serum levels of BDNF

decreased significantly compared to the control group.
Additionally, significant correlations were found between

WHOQOL-BREF scores and various clinical, laboratory, and

instrumental parameters, including the duration of the disease,

fasting blood glucose, glycated hemoglobin levels, BDNF, and
blood flow velocity in the carotid and vertebral arteries. The

study highlights the importance of the WHOQOL-BREF

questionnaire in assessing the quality of life in this patient

population and identifies BDNF as a valuable marker for brain

ischemia in T2DM patients undergoing hemodialysis.

2181-

1415/©

2024 in Science LLC.

DOI:

https://doi.org/10.47689/2181-1415-vol5-iss9/S-pp92-98

This is an open access article under the Attribution 4.0 International

(CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/deed.ru)

Keywords:

quality of life,

WHOQOL-BREFis,

BNDF,

hemodialysis.

1

PhD, Hemodialysis Department, Republican Specialized Scientific and Practical Medical Center of Endocrinology

named after academician Ya.Kh. Turakulov of the Ministry of Health of the Republic of Uzbekistan.

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Miya ishemiyasi darajasini baholashda gemodializda

2-toifa qandli diabet bilan og

‘

rigan bemorlarda WHOQOL-

BREF so

‘

rovnomasi va BNDF neyromarkerining ahamiyati

ANNOTATSIYA

Kalit so‘zlar

:

hayot sifati,

WHOQOL-BREFis,

BNDF;

gemodializ.

Ushbu tadqiqot hayot sifatini baholash vositasi bo‘lgan

WHOQOL-

BREF so‘rovnomasining ahamiyatini va surunkali

buyrak kasalligi (CKD) bilan asoratlangan 2-toifa qandli diabet

(T2DM) bilan og‘rigan bemorlarda miyadan olingan

neyrotrofik

omil

(BDNF)

biomarkerining

ahamiyatini

baholashga

qaratilgan.) gemodializ olayotganlar. 2019-yil 1-yanvardan

2020-yil 31-dekabrgacha dasturlashtirilgan gemodializdan

o‘tayotgan T2DM va III bosqich surunkali buyrak
etishmovchiligi (CRF) bo‘lgan jami 90 nafar bemor tekshirildi.

Bu bemorlar surunkali miya yarim ishemiyasi (SCI) og‘irligiga

qarab uch guruhga bo‘lingan.). Natijalar shuni ko‘rsatdiki, CCI

darajasi oshgani sayin, qon zardobida BDNF darajasi nazorat
guruhiga nisbatan sezilarli darajada kamaydi. Bundan tashqari,

WHOQOL-

BREF ko‘rsatkichlari va turli klinik, laboratoriya va

instrumental ko‘rsatkichlar, shu jumladan kasallikning

davomiyligi, ochlikdagi glyukoza, glyukozalangan gemoglobin

darajasi, BDNF va karotid va vertebral arteriyalarda qon oqimi

tezligi o‘rtasida sezilarli bog‘liqlik aniqlandi. Tadqiqot

WHOQOL-

BREF so‘rovining ushbu bemor populyatsiyasining

hayot sifatini baholashda muhimligini ta’kidlaydi va BDNFni

gemodializdan o‘tayotgan T2DM bemorlarida miya ishemiyasi

uchun qimmatli marker sifatida aniqlaydi.

Значимость опросника WHOQOL

-

BREF и нейромаркера

BNDF у больных сахарным диабетом 2 типа,

находящихся на гемодиализе, в оценке степени
ишемии головного мозга

АННОТАЦИЯ

Ключевые слова:

качество жизни,

WHOQOL-BREFis.

BNDF;

гемодиализ

.

Целью

данного

исследования

является

оценка

значимости опросника WHOQOL

-

BREF, инструмента для

оценки качества жизни, и биомаркера нейротрофического

фактора мозга (BDNF) у больных сахарным диабетом

2 типа (СД2), осложненным хронической болезнью почек

(ХБП), находящихся на гемодиализе. В период с 1 января

2019 года по 31 декабря 2020 года было обследовано

90

пациентов

с

СД2

и

хронической

почечной

недостаточностью (ХПН) III стадии, находящихся на

программном гемодиализе. Эти пациенты были разделены

на три группы в зависимости от тяжести хронической

ишемии мозга (ХИМ). Результаты показали, что по мере
увеличения степени ХИМ сывороточные уровни BDNF

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значительно снижались по сравнению с контрольной

группой. Кроме того, были выявлены значимые
корреляции между показателями опросника WHOQOL

-BREF

и

различными

клиническими,

лабораторными

и

инструментальными

параметрами,

такими

как

длительность заболевания, уровень глюкозы натощак,
уровни гликированного гемоглобина, концентрация BDNF

и скорость кровотока в сонных и позвоночных артериях.

Это

исследование

подчеркивает

важность

использования опросника WHOQOL

-

BREF для оценки

качества жизни данной группы пациентов, а также

определяет BDNF как ценный маркер ишемии мозга у
пациентов с СД2, находящихся на гемодиализе.

SUMMARY
The aim of the research is

to study the significance of quality-of-life indicators

and

brain-derived neurotrophic factor BNDF in patients with type 2 diabetes mellitus

complicated by chronic kidney disease and receiving programmed hemodialysis.

MATERIAL AND METHODS

We examined and surveyed a total of 90 patients with type 2 diabetes mellitus and

stage III CRF on program hemodialysis from January 1, 2019, to December 31, 2020. Of

these, 43 were women and 47 were men. The average age of men was 67 ± 4.2 years, and
the average age of women was 64 ± 5.6 years. The control group consisted of 20 patients

of the corresponding age. The number of hemodialysis sessions in patients ranged from
2 to 162.

RESULTS

According to the degree of chronic cerebral ischemia (CCI), patients were divided

into 3 groups: Group 1

–

36 (40.0%) patients with stage 5 diabetic nephropathy with

grade 1 CCI; Group 2

–

32 (35.5%) patients with stage 5 diabetic nephropathy with grade

2 CCI; Group 3

–

22 (24.4%) patients with stage 5 diabetic nephropathy with grade 3 CCI.

Research into biomarkers for diagnosing various brain lesions has been ongoing

for over 20 years, but the ideal biomarker has not yet been found. Among biochemical
markers, the determination of the level of neurospecific proteins is actively being
studied. In patients with type 2 diabetes mellitus undergoing programmed hemodialysis,
this issue is also relevant due to frequent cerebrovascular complications, but few such
studies have been conducted.

CONCLUSION

Questionnaire for determining quality of life indicators

–

WHOQOL-BREFis the

most sensitive and informative for determining the quality of life in patients with type
2 diabetes mellitus with CKD;

2) Serum levels of BDNF in groups of patients with type

2 diabetes mellitus significantly decrease compared to the control group as the degree of
CCI increases.

2) Significant correlations were identified WHOQOL-BREF and laboratory and

instrumental parameters. A correlation was found with the duration of the disease,
fasting glycemia levels, glycated hemoglobin levels, BNDF in the blood, and blood flow
velocity in the carotid and vertebral arteries.

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INTRODUCTION

Diabetes mellitus (DM) is a global health problem due to its steadily increasing

prevalence, reaching pandemic proportions, significant pharmacoeconomic costs for

timely diagnosis and the search for effective treatment, high social losses, and mortality,

including among the working-age population [1,2].

Brain damage is considered the most common and dangerous complication of

diabetes mellitus, characterized by multiple clinical manifestations, which is due to the

involvement of both central and peripheral structures, and starts in the earliest stages of

type 2 diabetes mellitus (type 2 diabetes).

Chronic kidney disease (CKD) is an inevitable and natural outcome of most

nephropathies, regardless of their nature, including type 2 diabetes [3,4]. At the same

time, the spectrum of chronic kidney diseases has significantly expanded over the past

decades, which is explained primarily by the general aging of the population and the

increase in the incidence of arterial hypertension, diabetes mellitus, and atherosclerosis

with an increase in vascular lesions of the kidneys. As a result, in recent years there has

been a tendency towards a steady increase in the number of patients suffering from CKD

[5, 6]. According to various data, CKD is detected in 100 to 600 people per 1 million

adults worldwide and increases with age per 1 million people, in Russia

–

from 212 to

595 per 1 million people. [7, 8].

There is growing interest worldwide in the use of common tools for the early

detection of cerebrovascular complications by assessing QOL in a wide range of diseases

and conditions. Particular attention is being paid to simple and accessible research tools,

including a questionnaire WHOQOL-BREF.[9, 10].

There are only a few publications in the literature devoted to the study of this issue

in patients suffering from CKD and receiving hemodialysis. In addition, the contribution

of cerebrovascular complications is unclear. CKD in the deterioration of quality-of-life

indicators in this category of patients.

Brain-derived Neurotrophic Factor (BDNF) is one of the best-characterized

members of the neurotrophin family, which has received much attention in recent years.

It is considered one of the key mediators of neuronal survival and recovery, and a

decrease in BDNF levels is a common mechanism underlying the development of various

neurodegenerative diseases.

All of the above served as the reason for this study.

The aim of this research is

to study the significance of quality of life indicators

and

brain-derived neurotrophic factor BNDF in patients with type 2 diabetes mellitus

complicated by chronic kidney disease and receiving programmed hemodialysis.

MATERIAL AND METHODS

We examined and surveyed a total of 90 patients with type 2 diabetes mellitus and

stage III CRF on program hemodialysis from January 1, 2019 to December 31, 2020.

Of these, 43 were women and 47 were men. The average age of men was 67 ± 4.2 years,

and the average age of women was 64 ± 5.6 years. The control group consisted of

20 patients of the corresponding age. The number of hemodialysis sessions in patients

ranged from 2 to 162.

All 90 patients underwent all studies, including general clinical (complete blood

count, complete urine analysis and according to Nechiporenko), biochemical (blood

sugar, glycemic profile, HbA1C, urea, creatinine, blood electrolytes, lipid spectrum,

coagulogram, etc.), hormonal blood tests (C-peptide, insulin) of the research laboratory

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of the RSNPMC of Endocrinology of the Ministry of Health of the Republic of Uzbekistan

ECG, ultrasound of internal organs, Dopplerography of the main arteries of the head, if

necessary, patients were referred for additional examination

–

X-ray, ultrasound of

internal and genital organs, consultation with a cardiologist, neurologist, nephrologist,

ophthalmologist, surgeon, and other studies. We assessed the quality of life of patients

before hemodialysis and in the dynamics of treatment using the WHO Short Form Quality

of Life Questionnaire (WHOQOL-BREF) and the Hamilton Depression Scale.

Statistical calculations were performed in the Microsoft Windows software

environment using the Microsoft Excel-2007 and Statistica version 6.0, 2003 software

packages. The data obtained are reflected in the dissertation as M±m, where M is the

average value of the variation series, and M is the standard error of the average value.
The reliability of differences between independent samples was determined using the
Mann-Whitney and Student methods.

According to the degree of chronic cerebral ischemia (CCI), patients were divided

into 3 groups: Group 1

–

36 (40.0%) patients with stage 5 diabetic nephropathy with

grade 1 CCI; Group 2

–

32 (35.5%) patients with stage 5 diabetic nephropathy with grade

2 CCI; Group 3

–

22 (24.4%) patients with stage 5 diabetic nephropathy with grade 3 CCI.

RESULTS AND DISCUSSION

Table 1 shows the distribution of examined patients by gender and age.

Table 1.

Distribution of patients by gender and age

Age, years

Number of men

Number of women

18-44 (young age)

11 (23.4%)

10 (23.3%)

45-59 (average age)

16 (34.0%)

11(25.6%)

60-74 (old age)

18 (38.3%)

20(46.5%)

75 and older (senior age)

2 (4.3%)

2 (4.6%)

Total: n = 90

47 (52.2%)

43(47.8%)

As can be seen from Table 1, patients in the age category from 60 to 74 years

predominated among both men and women

–

18/20 cases, respectively.

Table 2 provides a comparative analysis of the content of brain-derived

neurotrophic growth factor (BNDF) in the serum of patients in the compared groups.

Table 2.

Comparative analysis of the content of brain-derived neurotrophic growth factor

(BNDF) in the serum of patients in the compared groups

Note:

Normal BDNF levels are from 15 to 24 pg/ml

Indicator

Control

group

1

group

2

group

3

group

p-value

BDNF, ng/ml

21.6

±

1.23

8.12

±

0.28

6.17

±

1.02

4.02

±

0.09

0,001

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As shown in Table 2, serum BDNF levels in groups of patients with type 2 diabetes

mellitus significantly decreased compared to the control group as the degree of CCI

increased.

Next, to assess the validity of the questionnaire WHOQOL-BREF The most

significant clinical laboratory and functional indicators were selected:

–

duration of the

disease, fasting glycemia levels, glycated hemoglobin level, blood flow velocity in the

carotid artery, in the vertebral artery. The results of the correlation calculations are

presented in Table 3.

Table 3.

Correlation relationship (R) of the values of the WHO short questionnaire

WHOQOL-BREF with laboratory and instrumental indicators

Questionna

ire

Glycemia

On an

empty

stomach

mmol/l

HbA1C

%

BNDF in

blood,

ng/ml

Duration

of illness,

years

Blood flow

velocity

In the

carotid

artery

Blood flow

velocity

In the vertebral

artery

WHOQOL-

BREF

0.67

0.59

0.64

0.73

0.68

0.76

As can be seen from Table 3, significant correlations were identified. WHOQOL-

BREF and laboratory and instrumental parameters. A correlation was found with the

level of fasting glycemia, glycated hemoglobin, BNDF in the blood, duration of the disease,

and blood flow velocity in the carotid artery, in the vertebral artery.

Thus, all the above data indicate the need to use quality of life assessment,

determining levels BNDF in patients with type 2 diabetes and CKD to develop measures

to prevent the development of stroke in patients on programmed hemodialysis.

CONCLUSIONS

1) Questionnaire for determining the quality of life indicators

–

WHOQOL-BREF is

the most sensitive and informative for determining the quality of life in patients with

type 2 diabetes mellitus with CKD.

2) Serum levels of BDNF in groups of patients with type 2 diabetes mellitus

significantly decrease compared to the control group as the degree of CCI increases.

3) Significant correlations were identified WHOQOL-BREF and laboratory and

instrumental parameters. A correlation was found with the duration of the disease,

fasting glycemia levels, glycated hemoglobin levels, BNDF in the blood, and blood flow

velocity in the carotid and vertebral arteries.

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Filimonova T.A., Karakulova Yu.V. The role of a brain-derived neurotrophic

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