Доктор ахборотномаси № 3.1 (96)—2020
40
УДК 616.61-002:616.379-008.64
RISK FACTORS FOR THE DEVELOPMENT OF DIABETIC NEPHROPATHY
IN PATIENTS WITH TYPE 1 DIABETES
B. K. Badridinova
Bukhara state medical institute, Bukhara, Uzbekistan
Keywords:
diabetic nephropathy, children, adolescents, clinical and epidemiological risk factors, metabolic risk fac-
tors.
Таянч сўзлар:
диабетик нефропатия, болалар, ўсмирлар, клиниик ва эпидемиологик хавф омиллари, метобо-
лик хавф омиллари.
Ключевые слова:
диабетическая нефропатия, дети, подростки, клинико-эпидемиологические факторы риска,
метаболические факторы риска.
The article presents data from a study that included 150 patients with type 1 diabetes mellitus (type 1 diabetes)
aged 6 to 18 years, who were registered at the Bukhara regional dispensary for 2018 - 2019. The study made it possi-
ble to study the clinical and epidemiological indicators of children and adolescents with type 1 diabetes in the city of
Bukhara. We were able to identify priority risk factors for the development of diabetic nephropathy, which included
age, onset of sexual development, anthropometry feature (tall), female sex. Adverse metabolic factors that save the
development of diabetic nephropathy in children and adolescents with type 1 diabetes include high hyperglycemia at
the onset of the disease. Arterial hypertension, dyslipidemia, development of diabetic retinopathy are not among the
main risk factors for diabetic nephropathy in children and adolescents.
ҚАНДЛИ ДИАБЕТ 1-ТИПГА ЧАЛИНГАН БЕМОРЛАРДА ДИАБЕТИК НЕФРОПАТИЯ
РИВОЖЛАНИШИНИНГ ХАВФ ОМИЛЛАРИ
Б. К. Бадридинова
Бухоро давлат тиббиѐт институти, Бухоро, Ўзбекистон
Мақолада 2018 йилдан 2019 йилгача Бухоро вилояти диспансерида рўйхатга олинган 6 ѐшдан 18 ѐшгача
бўлган 1-тоифа диабет касаллиги (1-тоифа диабет) билан касалланган 150 нафар беморни ўз ичига олган
тадқиқот маълумотлари келтирилаган. Тадқиқот Бухоро шаҳрида диабетнинг биринчи турига чалинган бола-
лар ва ўсмирларнинг клиник-эпидемиологик кўрсаткичларини ўрганишга имкон беради. Биз диабетик нефро-
патия ривожланиши, антропометрия хусусияти (юқори ўсиш), аѐл жинси. 1-тоифа диабетга чалинган болалар
ва ўсмирларда диабетик нефропатия ривожланишини тежайдиган салбий метаболик омилларга касаллик
бошланганда юқори гипергликемия сабаб бўлиши керак. Артериал гипертензия, дислепидемия, диабетик ре-
тинопатиянинг ривожланиши болалар ва ўсмирларда диабетик нефропатиянинг асосий хавф омилларидан
бири эмас.
ФАКТОРЫ РИСКА РАЗВИТИЯ ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ У БОЛЬНЫХ САХАРНЫМ
ДИАБЕТОМ 1 ТИПА
Б. К. Бадридинова
Бухарский государственный медицинский институт, Бухара, Узбекистан
В статье приведены данные исследования, которое включало 150 пациентов с сахарным диабетом тип 1
(СД тип 1) в возрасте от 6 до 18 лет, состоящих на диспансерном учете в Бухарском областном диспансере за
2018 - 2019 г. Проведенное исследование позволило изучить клинико-эпидемиологические показатели детей и
подростков с СД 1 типа в городе Бухары. Нам удалось выявить приоритетные факторы риска развития диабе-
тической нефропатии, которые включали возраст, начала полового развития, особенность антропометрии
(высокий рост), женский пол. Неблагоприятным метаболическим фактором, способствующим развитию диа-
бетической нефропатии у детей и подростков с СД 1 типа, следует отнести высокую гипергликемию в дебюте
заболевания. Артериальная гипертензия, дислипидемия, развитие диабетической ретинопатии не входят в чис-
ло основных факторов риска диабетической нефропатии у детей и подростков.
Diabetic nephropathy (DN) is one of the most formidable, frequent, and prognostically unfa-
vorable complications of diabetes mellitus. Early diagnosis and prognosis of kidney damage are of
fundamental importance for DN [1]. In this regard, the search continues for early diagnostic mark-
ers, as well as risk factors for the development of this complication in patients with type 1 diabetes
mellitus (DM1).
It is known that the main risk factors for the development of DN in adult patients with type 1
diabetes are long-term decompensation of the disease, hyper- / dyslipidemia, arterial hypertension,
Оригинальная статья
Доктор ахборотномаси № 3.1 (96)—2020
41
and the patient's gender [2–3]. It is believed that the presence of diabetic retinopathy (DR) indi-
rectly indicates a high risk of DN due to the universality of microangiopathy in T1DM [2]. The
available research data convincingly prove the importance of genetic factors in the development of
DN, additionally indicating the features of the development of nephropathy in T1DM in the struc-
ture of diabetic microangiopathy [4]. It should be noted that at present, the clinical and epidemio-
logical risk factors for the development of DN in childhood remain less studied.
Goal of the research.
Identification of risk factors for diabetic nephropathy in patients with
type 1 diabetes.
Materials and methods.
The study included 150 patients with type 1 diabetes aged 6 to 18
(12.8 ± 0.8 years). All patients were followed up at the Bukhara Regional Dispensary in the city of
Bukhara from 2018 to 2019. The degree of compensation of the disease was assessed by the pa-
rameters of glycosylated hemoglobin (HbA1c) [5]. The values of lipid and lipoprotein parameters
in blood serum were determined on a biochemical analyzer "Mindray" (China). DN diagnosis was
carried out according to the algorithms of specialized medical care for patients with diabetes. Na-
tional standards of care for patients with diabetes define the need for annual screening at UIA for
all patients from the moment of diagnosis. The exception, according to these standards, is repre-
sented by patients with type 1 diabetes who became ill in early childhood and post-puberty. In this
category of patients, it is recommended to start screening 5 years after diagnosis [6]. Diagnosis of
changes in the fundus vessels was carried out by means of reverse and direct ophthalmoscopy, ex-
amination of the retina using a slit lamp using aspherical lenses. In order to verify the DR, photo-
graphing of the fundus was carried out using a fundus camera (Topcon, Japan). Measurement of
blood pressure (BP) was carried out on an outpatient basis during routine examinations of patients
using the standard method of N.S. Korotkov. In patients with DN, the indicators of systemic blood
pressure were taken into account at the time of verification of this complication, before the initia-
tion of pathogenetic therapy with drugs of the group of angiotensin converting enzyme inhibitors.
Assessment of blood pressure and growth indicators was carried out by the method of centile ta-
bles, traditional for pediatrics. Columns of centile tables show the quantitative boundaries of the
trait in a certain proportion or percentage (centile) of healthy children of a given age and gender.
In the zone from the 25th to the 75th centile are the average values of the analyzed feature.
The data obtained were processed on a personal computer using MS Excel 2010 software.
Data are presented as M ± SD. A 95% confidence interval (CI) was calculated for the means and
frequencies. The differences in all parameters of the examined patients were assessed using the
Waller-Duncan test; p <0.05 was considered statistically significant.
Results and its discussion.
During the observation period of patients in a specialized endo-
crinology center, 150 children and adolescents were examined in order to identify DN. The exami-
nation was performed according to the algorithms for the provision of medical care, with the ex-
clusion of physiological albuminuria, and differential diagnosis with primary renal pathology in
type 1 diabetes. According to the data of long-term follow-up of the surveyed contingent of pa-
tients, among the most significant differential diagnostic characteristics of DN, the following were
identified: 1) age over 11 years, 2) development of nephropathy after the onset of the underlying
disease, 3) absence of clinical manifestations at an early stage of DN, 4) no changes in urinary sed-
iment, sterile urine cultures, 5) lack of effect of therapy with angiotensin converting enzyme inhib-
itors.
During the study, specific diabetic kidney damage was diagnosed in 56 patients aged 11–18
years, 44 adolescents of the same age period had no signs of diabetic kidney damage. No cases of
DN detection in patients of an earlier age (n = 50) were registered. DN in the examined patients
was detected in almost a quarter of adolescents over 11 years old, accounting for 37.3% in this age
group. At the same time, the duration of the disease was different and was not decisive in the de-
velopment of DN. According to the literature, DN develops on average 10 years after the onset of
DM in adult patients. As the results of this study show, in adolescence, it would be wrong to con-
sider the duration of diabetes as a factor determining the high likelihood of developing DN. So, the
B. K. Badridinova
Доктор ахборотномаси № 3.1 (96)—2020
42
minimum period for the progression of diabetes from the moment of manifestation was 2 years.
The data obtained are consistent with the practical recommendations for early diagnosis of
nephropathy in type 1 diabetes [6]. When analyzing indicators of the duration of diabetes as one of
the determining risk factors for the development of nephropathy in adult patients in groups of pa-
tients aged 11 to 18 years with DN (mean age - 14.1 ± 1.1 years, n = 100) and without DN (14.3 ±
0.9 years, n = 50), no differences were found: 5.1 ± 0.7 and 4.9 ± 0.3 years, respectively (p> 0.05)
(table 1). Physiological features of puberty, accompanied by psychosocial personality formation,
determine the inclusion of patients with type 1 diabetes at this age in the group of increased risk of
developing specific complications of diabetes as a result of the formation of relative insulin re-
sistance due to increased secretion of counterinsular hormones [7]. In this case, the participation of
growth hormone and insulin-like growth factors I in the development of hyperfiltration and renal
hypertrophy in the early stages of diabetes. Experimental studies have shown that the administra-
tion of somatostatin (a blocker of growth hormone and growth factors) to rats with induced diabe-
tes was able to prevent an increase in kidney size and the development of hyperfiltration, and this
also contributed to a decrease in MAU in clinical trials [10]. In the majority of patients (83.9%)
DN was diagnosed at the MAU stage, and in 16.1% of patients at the stage of proteinuria with pre-
served nitrogen excretory function of the kidneys. Attention is drawn to the fact that children and
adolescents do not have DN of the stage of chronic renal failure, the development of which is de-
termined by the duration of exposure to chronic hyperglycemia [2].
The role of the system "somatotropic hormone-insulin-like growth factors" is evidenced by
the fact that diabetic microangiopathy almost rarely developed in patients in whom diabetes was
combined with pituitary dwarfism [11]. The incidence of DR and other specific complications of
diabetes (distal polyneuropathy, hiropathy, cataract) did not differ statistically in the groups of pa-
tients with DN and without nephropathy (0.257 [95% CI 0.157–0.356], p> 0.05). It should be not-
ed that there was a tendency towards a higher incidence of DR in the group of patients with DN in
the MAU stage as compared with patients without DN. Retinopathy was diagnosed in 15% of pa-
tients with diabetic kidney damage and in 12% of patients without nephropathy. The data obtained
and individual clinical observations do not allow us to classify the presence of DR as a risk factor
for the development of nephropathy in patients with T1DM in childhood. This circumstance re-
flects the peculiarities of the course of these complications in the structure of universal diabetic
microangiopathy. To date, it has been convincingly proven that the development of complications
of diabetes is most associated with decompensation of carbohydrate metabolism (Russian Consen-
sus on the treatment of diabetes in children and adolescents) [12]. In order to study the influence of
carbohydrate metabolism indicators on the development of DN in children and adolescents, we
studied the HbA1c level in two groups: 1) patients with T1DM complicated by DN (56); 2) pa-
tients with type 1 diabetes without DN (94). The HbA1c levels did not statistically significantly
differ in the groups of patients with and without DN: 9.48 ± 3.04 and 8.91 ± 2.06%, respectively
(p> 0.05).
We emphasize that the level of HbA1c in both groups and individual samples was higher
than the known normal values. Considering that in the compared groups the incidence of the main
complications specific to diabetes (retinopathy, neuropathy) did not differ statistically, the ob-
tained result allows us to conclude that the degree of chronic hyperglycemia has almost the same
significance as a risk factor for both DN and other complications of diabetes in children and ado-
lescents with type 1 diabetes. However, HbA1c indices during the first year after the onset of dia-
Оригинальная статья
Age
Patients with DN
n
Patients without DN
n
6-10 years
50
100%
11-18 years
56
37,3%
44
62,7%
Table 1.
Indicators of the presence of nephropathy in the age aspect
Доктор ахборотномаси № 3.1 (96)—2020
43
betes were higher in the group of patients
with DN compared with patients without
diabetic kidney damage, amounting to
9.29 ± 2.07 and 8.54 ± 1.19%, respective-
ly (p <0.05 ); frequency HbA1> 8.9% -
0.767 [95% CI 0.637-0.898] (Fig. 1).
The data obtained should be taken
into account when forming a "risk group"
for the development of nephropathy in
type 1 diabetes in childhood. In this re-
gard, it seems essential that the compensa-
tion of the disease from the first days of
the onset of diabetes can be a significant
factor in the prevention of DN in children
and adolescents. It is known that, along
with hyperglycemia, dyslipidemia is a risk
factor for the development and progression of DN [3, 9, 13].
In the present study, we studied the effect of lipid metabolism disorders on the development
of DN in adolescents with T1DM. 79 adolescents aged 12 to 18 years with type 1 diabetes were
examined. Two groups were formed: the 1st group consisted of 38 patients with DN, the 2nd
group included 41 patients without diabetic kidney damage. The study analyzed the differences in
lipid profile in patients with DN (group 1) and without diabetic kidney damage (group 2). The to-
tal cholesterol level did not differ statistically in patients of groups 1 and 2, amounting to 4.71 ±
1.04 and 4.73 ± 0.08 mmol / L, respectively (p> 0.05). The triglyceride level was higher in patients
with DN than in the group of patients without DN (p <0.05). Low density lipoprotein (LDL) con-
tent - 2.49 ± 0.14 versus 2.62 ± 0.07 mmol / L, respectively (p> 0.05); the level of very low densi-
ty lipoproteins (VLDL) was significantly higher in patients with DN (0.49 ± 0.05 mmol / L) in
comparison with patients without DN (0.40 ± 0.03 mmol / L, p <0.03 ). At the same time, the indi-
cator of high density lipoproteins (HDL) was lower in patients with DN compared with patients
without nephropathy (p <0.03). The atherogenic coefficient was lower in group 2 and amounted to
1.78 ± 0.075 versus 1.97 ± 0.15 in group 1 (p> 0.05) (Fig. 2). Indicators of total cholesterol and
lipoprotein fractions in adolescents with DN did not go beyond the normal range. However, atten-
tion is drawn to the fact that in adolescents with DN the levels of potentially atherogenic fractions
were higher than in patients without DN.
Conclusion.
Thus, the study of clinical and epidemiological indicators in type 1 diabetes in
the population of children and adolescents in the city of Bukhara makes it possible to take into ac-
count among the priority risk factors for the development of DN the age of onset of sexual devel-
Fig. 1. Indicators of the level of glycosylated hemoglo-
bin in patients with diabetic nephropathy (group 1) and
without nephropathy (group 2) at the onset of type 1
diabetes mellitus (p <0.05).
Fig. 2. Indicators of blood lipids in patients with diabetic nephropathy (group 1)
and without diabetic kidney damage (group 2) (p <0.05)
B. K. Badridinova
Доктор ахборотномаси № 3.1 (96)—2020
44
opment, the peculiarity of anthropometry (high growth). The unfavorable metabolic factors that
determine the development of nephropathy in children and adolescents with type 1 diabetes in-
clude a high degree of chronic hyperglycemia at the onset of the disease.
References:
1. Кисельникова О.В. Прогнозирование и ранняя диагностика диабетической нефропатии у детей: Дис.канд.
мед.наук. Ярославль; 2017.
2. Смирнов И.Е., Кучеренко А.Г., Смирнова Г.И. Бадалян А.Р. Диабетическая нефропатия. Российский педи-
атрический журнал. 2015; 18(4): 43-50].
3. Bulletin of Medical Science No. 2 (10) 2018, 25.
4. Dedov I.I., Shestakova M.V., Vikulova O.K. Epidemiology of Diabetes Mellitus in the Russian Federation: Clini-
cal and Statistical Analysis Based on Data from the Federal Register of Diabetes Mellitus. Diabetes. 2017; 20 (1):
13–41.
5. Dedov I.I., Peterkova V.A., Kuraeva T.L. Russian consensus on the treatment of diabetes mellitus in children and
adolescents // Pediatrics. - 2010. - No. 1. - P. 16–23. 13.
6. Diabetic nephropathy. Modern view of the problem Altai State Medical University, Barnaul Zharikov A.Yu.,
Schekochikhina R.O. 2018.
7. Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of
prevalence and risk factors. J Nephropharmacol. 2016;5(1):49–56.
8. Magee C, Grieve DJ, Watson CJ, Brazil DP. Diabetic nephropathy: a tangled web to unweave. Cardiovasc Drugs
Ther. 2017;31(5–6):579–92.
9. Mahaboob Khan Sulaiman Diabetic nephropathy: recent advances in pathophysiology and challenges in dietary
management; Diabetology & Metabolic Syndrome volume 11, Article number: 7 -2019.
10. Papadopoulou-Marketou N, Paschou SA, Marketos N, Adamidi S, Adamidis S, Kanaka-Gantenbein C. Diabetic
nephropathy in type 1 diabetes. Minerva Med. 2018;109(3):218–28.
11. Satirapoj B. Nephropathy in diabetes. Adv Exp Med Biol. 2012; (771): 107–122.
12. WHO Diabetes Fact sheet Updated November 2017.
13. Zhang J, Liu J, Qin X. Advances in early biomarkers of diabetic nephropathy. Rev Assoc Med Bras. 2018;64(1):85
–92.
Оригинальная статья
