Научная статья на тему 'Insulin resistance in children and teenagers with exogenous constitutive obesity'

Insulin resistance in children and teenagers with exogenous constitutive obesity Текст научной статьи по специальности «Клиническая медицина»

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CHILDREN / TEENAGERS / OBESITY / INSULIN RESISTANCE / SEX HORMONE-BINDING GLOBULIN

Аннотация научной статьи по клинической медицине, автор научной работы — Rakhimovа Gulnara Nishanovna, Azimova Shakhnozakhon Sharafutdinovna

The study consisted of 100 children and teenagers with exogenous constitutive obesity (ECO) of Uzbek population aged from 6 to 16. The mean age of the patients was 11,7±0,25 years old. The conducted researches showed that the values НОМА>97 percentile occurred more often in boys than in girls at all stages of sexual development. According to our data, the indicators HOMA-IR according to Tanner 1 ≥1,4 and Tanner 2-5 ≥1,8 can be used as criterion for intensive search of components of metabolic syndrome. The level of SHBG in obesity, regardless sex and stage of sexual development, is significantly lower than in the control group; herewith, it is lower in boys than in girls.

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Текст научной работы на тему «Insulin resistance in children and teenagers with exogenous constitutive obesity»

angiitis obliterans 5 (5.2%), nonspecific aortoarteriitis in 3 (3.2%), diabetic angiopathy in 9 (9.3%) patients. The average age of the surveyed — 52 years. There were used a complex clinical, laboratory, instrumental, statistical research methods and beam diagnostics. In compiling the computer program in accordance with the algorithm for improving the diagnosis of patients with chronic peripheral arterial occlusive disease of the lower limbs used modern programming language — BorlandDelphi 7.

Results and discussion. For diagnosis chronic peripheral arterial occlusive disease of the lower limbs patients passed a comprehensive examination, including innovative research methods. According to the algorithm of diagnosis clinical examination include: complaints of patients, etiological factors, objective study, functional tests, the determination of the shoulder-ankle index oxitenzometry.

Laboratory studies include: general clinical blood tests, blood chemistry, coagulation.

Radial diagnostics includes: ultrasound duplex sonography, MSCT angiography, x-ray angiography.

As a result of a comprehensive survey of patients with chronic peripheral arterial occlusive disease of the lower limbs formed the database, based on which is installed the correct diagnosis and treatment strategy is determined.

Based on the diagnostic algorithm of chronic peripheral arterial occlusive disease of the lower limbs developed by us, a computer program has been complied, which received a patent for Intellec-

tual Property Agency of the Republic of Uzbekistan (number DGU 02579 from 31.07.2012.).

A computer program consists of one project (Diag.dpr) and three modules (Modl.pas, Mod2.pas, Mod3.pas) and provides necessary image printouts for doctors.

When you click "OK" on the 2nd module screen appears. The relevant elements of the window are entered the necessary data (name of the patient, gender, age, as well as the results of the survey). The window of this module consists of three pages, "Clinical examination", "Laboratory tests" and "Radial diagnostics".

After entering the required data press the "Diagnosis" and displays a window 3rd modul. This window displays the results of the diagnosis, which if necessary can be printed or saved to a file.

Conclusions: In created by us diagnostic algorithm of chronic peripheral arterial occlusive disease of the lower limbs, were used available clinical and laboratory parameters. As a result, processing and entering data into a computer program is not only determined the most likely diagnosis of the three possible diseases — obliterating atherosclerosis, obliterating endarteritis and nonspecific aortoarteritis, but also creates a database for each patient. The use of this computer program greatly facilitates work and saves time of surgeons.

Using the developed diagnostic algorithm of chronic peripheral arterial occlusive disease of the lower limbs can achieve a statistically significant reduction in the frequency of diagnostic errors and to reduce the diagnosis time and determine the correct treatment strategy.

Refences:

1. Bokeria LA And others. Cardiovascular Surgery - 2013. Diseases and congenital anomalies of the system krovoobrascheniya.- M.: NTSSSH them. AN Bakuleva, - 2014. - 220 p.

2. Gavrilenko, A. B. and others. The results of surgical and conservative treatment ofpatients younger than 50 years with arterial lesions in the femoral-tibial segment//Annals of Surgery. - 2007. - № 2. - P. 49-53.

3. Zatevakhin II et al. Obliterans trombangiit. - M., - 2002. - 317 p.

4. Kohan EP et al. Selected lectures on angiologii. - M.: Nauka, - 2000. - 379 p.

5. Basil, etc. Diagnosis and treatment of nonspecific aortoarteritis: A Guide for vrachey. - M.: Iris, - 2003. - 144 p.

6. Yudin RY Thromboangiitis obliterans (clinic, diagnostics, treatment): Abstract. Dis. d. m. n. - M., - 2001. - 34 p.

7. Norgen L. et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)//J Vasc Surg. - 2007. - Jan; 45. - Suppl R. 65-67.

8. Resource El. URL: http://www.tiensmed.ru/news/obliteriit-v3a.html occlusive disease - causes, diagnosis, treatment (treatment date - 25/05/2014).

9. Resource E. URL: http://diabeticfoot.ru/d/176414/d/rossiyskiy_konsensus.pdf Russian consensus diagnosis and treatment of patients with critical extremities ischemia (reference date 05/25/2014).

DOI: http://dx.doi.org/10.20534/ESR-16-9.10-124-126

Rakhimova Gulnara Nishanovna, Head of the Department of Endocrinology, Tashkent Institute of Advanced Medical Studies, Ministry of Health of the Republic of Uzbekistan

E-mail: shahnoz74@yandex.com Azimova Shakhnozakhon Sharafutdinovna, Republican Specialized Scientific and Practical Medical Center of Endocrinology under the Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan

Head of the Department of Pediatric Endocrinology E-mail: shahnoz74@yandex.com

Insulin resistance in children and teenagers with exogenous constitutive obesity

Abstract: The study consisted of100 children and teenagers with exogenous constitutive obesity (ECO) of Uzbek population aged from 6 to 16. The mean age of the patients was 11,7±0,25 years old. The conducted researches showed that the values

Insulin resistance in children and teenagers with exogenous constitutive obesity

HOMA>97 percentile occurred more often in boys than in girls at all stages of sexual development. According to our data, the indicators HOMA-IR according to Tanner 1 >1,4 and Tanner 2-5 >1,8 can be used as criterion for intensive search of components of metabolic syndrome. The level of SHBG in obesity, regardless sex and stage of sexual development, is significantly lower than in the control group; herewith, it is lower in boys than in girls.

Keywords: children, teenagers, obesity, insulin resistance, sex hormone-binding globulin.

Insulin resistance (IR) is one of the main components of metabolic syndrome and is a reason for development of atherosclerotic changes in vessels, which creates prerequisites for appearance and fast progression of a range of serious diseases leading to early disability and early death.

Resistance to insulin in adults, as rule, is related to obesity, diabetes or impaired glucose tolerance, arterial hypertension, dyslipid-emia. There is more and more evidence that the appearance of insulin resistance syndrome can take place in childhood and teenage years [6; 7]. Before the attention is accentuated on cardio-vascular risks in IR, it is required to analyze what happens to the physiological IR (PIR) appearing during sexual development, because PIR can lead to phenotypic changes.

During sexual development, BMI increases slowly. Muscle and fat mass of the body increases in both sexes, but by the end of sexual development, fat represents bigger percentage of the total body mass in girls than in boys [8].

The increase of fat and BMI strongly correlates with insulin resistance, hence, they were proposed as potential mediators of pubertal changes of IR. However, according to some researchers, insulin resistance can appear during the period of sexual development in the absence of BMI changes [2; 6; 9; 10].

Unfortunately, the researches concerning insulin resistance depending on the degree of sexual development according to Tanner are not enough.

Goal of research: to evaluate insulin resistance in children and teenagers with exogenous constitutive obesity.

Materials and methods of research.

The study consisted of 100 children and teenagers with exogenous constitutive obesity (ECO) of Uzbek population aged from 6 to 16; out ofwhich, boys accounted for 54 (54,0%) and girls — 46 (46,0%). The mean age of the patients was 11,7±0,25 years old. All patients were divided according to their age, sex and stages of sexual development.

The control group included 71 healthy children and teenagers, among which, boys accounted for 38 (53,5%) and girls — 33 (46,5%) of respective age (mean age 11,1±0,33 years old).

All children and teenagers underwent the evaluation of anthropometric indicators: height, body mass, BMI, waist circumference (WC), hip ration (HR), WC/HR correlation. Body mass index was calculated according to Quetelet equation: BMI = weight/height 2 (kg/m 2). The criteria of excess body mass and obesity in children were defined according to the data of percentile tables of BMI (WHO) [10]. Waist circumference (WC) was evaluated according to age norms from 2 to 18 years old in compliance with the data [6] and criteria developed for Uzbek population [1]. The evaluation of sexual status was performed according to Tanner classification (1968). The volume of testicles was measured with the help of Prader orchidometer.

The level of glycated hemoglobin (HbA1c) was defined by colo-rimetric method. The level of sex hormone-binding globulin, IRI on empty stomach and in the course of glucose tolerance test (GTT) by method of RIA («Immunotech», Czech Republic). IR indicators were calculated according to HOMA equations (HOMA-IR index, Homeostasis Model Assessment) [4]. Regulated value of HOMA index in adults was accepted as 2,27 [2].

Statistical processing of the research results was conducted with the use of STATISTICA package (version 6.0). The data is presented in the form of mean arithmetic values and error of mean (M±m). The critical level of the value to check statistical hypotheses during the comparison of groups was 0,05.

Results and discussion.

The analysis of IRI level on empty stomach in the control group both in children and teenagers did not show significant difference from the stage of sexual development and sex. In boys and girls with ECO, regardless the stage of sexual development, IRI indicator on empty stomach was higher than the control, but it was significantly increased only in boys (Table 1.).

Indicators Children a ged 6 to 10 Teenagers a ged 10 to 16

Boys Girls Boys Girls

Tanner 1 Tanner 1 Tanner 2-3 Tanner 4-5 Tanner 2-3 Tanner 4-5

n= (C/ECO) 9/10 11/15 18/29 10/16 13/22 5/13

IRI on empty stomach Cont. 4,1±0,8 3,7±0,3 4,9±1,0 5,2±0,4 5,4±0,6 6,5±1,0

ECO 14,5±1,5 19,5±7,2 17,1±3,6 26,0±7,3 21,0±5,5 12,3±1,9

P 0,000 0,07 0,01 0,04 0,03 0,09

IRI after work Cont. 4,3±1,5 5,2±1,0 8,14±1,8 7,1±2,7 9,0±1,4 17,8±14,3

ECO 5,1±0,02 28,2±9,7 18,3±4,3 34,2±8,0 22,6±4,3 27,0±4,6

P 0,585 0,06 0,08 0,02 0,02 0,43

HOMA R Cont. 0,27±0,1 0,26±0,1 0,48±0,2 0,25±0,1 0,38±0,03 0,55±0,1

ECO 2,57±0,4 3,23±1,2 3,2±0,6 4,6±1,2 3,74±1,0 2,3±0,4

P 0,000 0,05 0,000 0,008 0,01 0,000

SHBG Cont. 116,1±14,3 87,9±18,4 69,8±6,7 81,3±9,1 63,1±12,9 55,9±8,0

ECO 38,1±17,5 50,5±19,2 47,4±7,1 55,5±11,4 41,0±6,8 59,2±14,2

P 0,003 0,19 0,04 0,13 0,11 0,89

р — significance between compared groups.

Table 1. - IRI and SHBG indicators in children and teenagers with ECO depending on sex and stage of sexual development

The analysis of IRI level after 2 hours after load with glucose in the course of GTT showed the increase of the indicator with the progression of puberty both in the control group and in ECO. IR was expressed in a less degree in children in the control group before the signs of puberty (I stage according to Tanner).

HOMA-IR index was significantly higher in patients with ECO than in healthy children regardless sex and stage of sexual development. Insulin resistance (the value of HOMA>97 percentile) was detected in ECO in, respectively, 44,4% and 18,2% boys and girls with stage 1 of sexual development according to Tanner. In teenagers (65,5% — boys and 40,9% — girls) in the initial stage of puberty, the cases of HOMA>97 percentile were also established. 68,8% of boys and 61,5% of girls with stage 4-5 according to Tanner had index HOMA>97 percentile. It should be noted that such values occurred in boys more often than in girls at all stages of sexual development.

Unfortunately, the matter of regulated values of HOMA-IR in children and teenagers remains open. In adult patients, its normal value does not exceed 2,27. M. Keskinetal [7] proposed to consider the index HOMA-IR greater than 3,5 as IR sign in teenagers with excess body mass. M. Lambertetal [8], in his research of diagnostics of metabolic syndrome, used the value of the 75th percentile of the index HOMA-IR.

However, in our researches, it was shown that HOMA-IR >1,8 (> 90 percentile) for age groups above 10 years old already indicates the presence of IR, and in children of the age group younger than 10 years old — HOMA-IR >1,4 (> 90 percentile) [3], which coincides with the data of Choi Yetal [5].

The analysis of the level of sex hormone-binding globulin (SHBG) depending on the stage of sexual development showed that in boys (stage 1 Tanner) of the control group, the level of SHBG was significantly higher than in girls, 116,1±14,3 nmol/l and 87,9±18,4 nmol/l (P=0,003) respectively. The analogical situation was observed in teenagers (stage 2-5 Tanner) from the control group (boys — 73,6±5,43 nmol/l; girls — 60,5±8,62 nmol/l; P=0,26). As for the level of SHBG depending on the age, it was significantly higher (P=0,04) in boys of the control group aged 6 to 10 compared with the indicator in the group aged 10 to 16. In girls, same tendency to the reduction of the hormone with age is observed. During the study of SHBG in children with ECO depending on sex, it was revealed that in the group aged from 6 to 10 (Tanner 1), the concentration of the hormone was insignificantly lower in boys (38,1±17,5 nmol/l) compared with the girls (50,5±19,2 nmol/l; P=0,65). In the group of patients aged from 10 to 16 (Tanner 2-5), on the contrary, it

was insignificantly higher in boys (50,1±6,01 nmol/l) than in girls (47,8±6,84 nmol/l; P=0,80). If we compare the level of SHBG in patients with ECO depending on the stage of sexual development, insignificant reduction is observed in boys (Tanner 1; P=0,43), and an increase compared with the level in teenagers (Tanner 2-5) is observed in girls (P=0,87).

The analysis conducted by us showed that SHBG level in children of the control group during pre-puberty (stage 1 Tanner) is higher; apparently, it is related to the low concentration of free sex hormones during this period. At the beginning of puberty, the level of SHBG reduces and the activity of free sex hormones increases.

During ECO, in the process of pre-puberty, the presence of IR leads to reduction of SHBG level. During the progression of obesity, it contributes to the increase of IR and weight gain during puberty.

According to the data received by Moran A. et al. [9], IR was stronger in girls than in boys. Although, this difference was noted at all stages of development according to Tanner, it was significantly important only at stage T4, which can be explained by small statistical power due to small size of selection. The differences in indicators between sexes can be partly, but not fully, explained by the differences in the degree of obesity, which is evaluated according to the thickness of the folds of fat. For each given value of BMI, such indicators as the thickness of folds of fat at the level of triceps and thickness of subscapular skinfold were higher in girls than in boys. The authors concluded that in healthy children, the stage of physiological IR starts at the very beginning of the puberty period. This stage is related to quick growth and development of a child and ends by the end of the puberty period. Although, the degree of IR is equally strongly related to BMI and degree of obesity at each stage of Tanner, the results of the undertaken research show that insulin resistance during the period of sexual development cannot be explained by only these factors.

Conclusions:

1. The values HOMA>97 percentile occurred more often in boys than in girls at all stages of sexual development.

2. Metabolic disorders are associated with insulin resistance as main component of metabolic syndrome in children with obesity.

3. The study of glycaemia and IRI on empty stomach with the calculation of HOMA-IR should be compulsory for children with progressing obesity.

4. The indicators of HOMA-IR according to Tanner 1 >1,4 and Tanner 2-5 >1,8 can be used as criterion for intensive search of components of metabolic syndrome.

References:

1. Азимова Ш. Ш., Рахимова Г. Н. Выявление риска развития метаболического синдрома по окружности талии у детей и подростков узбекской национальности. Патент № DGU 02583 от - 2012 г.

2. Бородина О. В. Оценка инсулинорезистентности у детей и подростков с ожирением//Проблемы эндокринологии. - 2003. -Т. 49 (6). - С. 8-9.

3. Рахимова Г. Н., Азимова Ш. Ш. Интегральная оценка факторов риска развития МС у детей и подростков с ожирением//МЭЖ. -2012. - № 3 (43).

4. Araki S., Dobashi K., Kubo K. Prevalence of 'obesity disease' and 'metabolic syndrome' in obese pediatric outpatients at the University Hospital of Occupational and Environmental Health, Japan//J UOEH. - 2008. - Vol. 30 (3). - P. 309-319.

5. Choi Y., Choi S., Kim H. et al.A higher burden of small low-density lipoprotein particles is associated with profound changes in the free androgen index in male adolescents//J Korean Med Sci. - 2011. - Vol.26 (4). - P. 534-539.

6. Jose R., David T., Pietrobelli A., Allison D. Waist Circumference Percentiles in Nationally Representative Samples of African-American, European-American, and Mexican-American Children and Adolescents//J Pediatr. - 2004. - Vol. 145. - P.43-44.

7. Keskin M., Kurtoglu S., Kendirci M. Homeostasis Model Assessment Is More Reliable Than the Fasting Glucose/Insulin Ratio and Quantitative Insulin Sensitivity Check Index for Assessing Insulin Resistance Among Obese Children and Adolescents//Pediatrics. -2005. - Vol. 115. - P. 500-503.

Assessment achievement of target levels of glycemic control in children with type 1 diabetes.

8. Lambert M., Paradis G., O'Loughlin J. Insulin resistance syndrome in a representative sample of children and adolescents from Quebec,

Canada//Int. J. Obes. Relat. Metab. Disord. - 2004. - Vol. 28. - P. 833-841.

9. Moran A., Jacobs D., Steinberger J. et al. Insulin resistance during puberty: results from clamp studies in 357 children//Diabetes. -

1999. - Vol. 48 (10). - P. 2039-2044.

10. Zimmet P., Alberti G., Kaufman F., Tajima N. The metabolic syndrome in children and adolescents-an IDF consensus report//Pediatric

Diabetes. - 2007. - Vol 8. - P. 299-306.

DOI: http://dx.doi.org/10.20534/ESR-16-9.10-127-129

Rakhimova Gulnara Nishanovna, Head of the Department of Endocrinology Tashkent Institute

of Advanced Medical Studies, Ministry of Health of the Republic of Uzbekistan E-mail: nasiba_ali@mail.ru Alimova Nasiba Usmanovna, Jr.researcher in Institute of Endocrinology Ministry of Health of Uzbekistan

Assessment achievement of target levels of glycemic control in children with type 1 diabetes, according to the National Register (NR) in Uzbekistan

Abstract: The Register cards included demographic data, duration of the disease, insulin therapy type, fasting glycemia parameters, postprandial glycemia, presence of late vascular complications, date and cause of death. Carbohydrate metabolism compensation parameters were assessed in compliance with ISPAD recommendations (2007). Analysis of carbohydrate metabolism compensation in children with type I diabetes mellitus during the National Register showed that as a whole in Uzbekistan optimum parameters of carbohydrate metabolism (fasting glycemia) were 30.5%. Suboptimal carbohydrate metabolism parameters were found in 14.0% of the children. Fasting glycemia level exceeding 8.0 mmol/l was registered in the majority of the patients (52.4%). When assessing postprandial glycemia optimum carbohydrate parameters in the children were found 38.2%. 40.0% of children had suboptimal carbohydrate metabolism parameters. 16.4% ofchildren were at the decompensation stage, that is, postprandial glycemia was higher than 2.5 mmol/l in these children. As per 2007 National Register the satisfying degree ofcompen-sation was failed to be achieved in 47.6% of children with type I diabetes mellitus that need changes in tactics of management.

Keywords: children, type 1 diabetes, glycemic control.

Type 1 diabetes mellitus (DM) in children is a chronic autoimmune disease, caused by destruction of pancreatic beta-cells and leads to absolute insulin deficiency.

In order to guarantee normal physical and intellectual development of children, to prevent the development of late vascular complications, blood glucose levels should be maintained within compensation rates. It is shown that elevation of the level of glycated hemoglobin (HbA1s) by 1% over 8%, existing for 3 months or more, increases the risk ofvascular events by40-50%. The results of a multinational study carried out recently in several countries, showed that only one third of children with diabetes have HbA1c level ofless than 8%, while the vast majority of young patients are in a state of chronic decompensation. This leads to early onset ofsevere microvascular complications such as diabetic retinopathy, diabetic nephropathy, neuropathy, disability and death in younger patients, as well as to the deterioration of physical health, psychological and social adaptation of children and adolescents, to communication problems with family members and with peers.

Recently, it was shown that the development of complications can occur after only a few years after the onset of the disease, particularly in childhood, which forces to address issues of intensification of treatment in pediatric practice.

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It is believed that stable compensation of carbohydrate metabolism achievement is harder in children rather than in adults. The main causes of inadequate compensation are as follows:

1) complete absence of insulin in the body with total dependence on exogenously administered insulin;

2) non-systematic meals;

3) non-permanent physical and school load;

4) The hormonal changes associated with growth and development;

5) behavioral problems associated with psychological difficulties;

6) frequent childhood infections.

In this regard, one of main problems of modern diabetology is the optimization and intensification of therapeutic approaches, which would improve both the therapeutic and cost-effectiveness of the treatment of children with diabetes. The quality of life and life expectance of children with diabetes, should not differ from those of their healthy peers.

The main criteria for the effectiveness of insulin therapy is to achieve and maintain normoglycemia, absence of severe hypoglycemia and episodes ofketoacidosis, as well as the normal rates of physical and sexual development of children. The consensus on the basic principles of the treatment of children and adolescents with type 1 diabetes (ISPAD Consensus for the Management of Type 1 Diabetes Mellitus in Children and Adolescens, 2007) recommends new criteria for the diagnosis and compensation of type 1 diabetes in children and adolescents (Table 1).

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