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https://doi.org/10.29013/ESR-19-11.12-40-43
Yuldasheva G. R., Doctor of medical sciences, senior researcher Tashkent Institute of Advanced Medical Education, Ministry of Health of the Republic of Uzbekistan E-mail: ludmilamedlib@mail.ru Khamrabaeva F. I., Doctor of medical sciences, Head of the department of gastroenterology, Tashkent Institute of Advanced Medical Education, Ministry of Health of the Republic of Uzbekistan
FEATURES OF THE BLOOD LEPTIN INDEX IN PATIENTS WITH CHRONIC PANCREATITIS ASSOCIATED WITH INSULIN RESISTANCE
Abstract. In recent decades doctors of almost all specialties have paid great attention to the problem of rapid increase in the frequency of metabolic syndrome - "pandemic of the 21st century". The purpose of this research was to study the characteristics of the blood leptin index in patients with chronic pancreatitis associated with insulin resistance. Measurement of the concentration of leptin in blood serum can be recommended for inclusion in the algorithm of examination of patients with CP combined with IR and can serve as additional markers of this condition.
Keywords: chronic pancreatitis, leptin, obesity, insulin resistance, metabolic syndrome.
Introduction of adiponectin. Peculiarities of polymorphism of
Currently, the rapid increase in the frequency of dopamine and leptin receptor genes associated with
metabolic syndrome (MS), "pandemic of the 21st MS with hyperactivity of the sympathetic nervous
century", continues according to WHO experts. The system were noted [4; 5].
main characteristics ofMS are an increase in visceral An important link in the pathogenesis of MS in
fat mass, insulin resistance, hyperinsulinemia [1; 3]. accordance with the lipocentric theory is abdominal-
In recent decades, doctors of almost all special- visceral adipose tissue. One of the main factors in
ties have paid great attention to this problem. Given MS can be considered android obesity. According to
current trends, the number of people suffering from S. A. Butrov et al. (2004), IR was detected in 88% of
MS will exceed half a billion people by the middle patients with the android type of obesity, and with
of this century. However, with timely diagnosis and the gynoid type of obesity only in 32% of patients. treatment, metabolic disorders can be reversible, Numerous studies have shown that hyperinsu-
or the severity of manifestations of MS may be cor- linemia leads to the depletion of the insular appara-
rected [2; 6]. tus of the pancreas (their mass decreases, the con-
In the formation of MS, the hyperactivity of the version of proinsulin into insulin is impaired). As a
hypothalamic-pituitary - adrenal system and sym- result, insulin secretion decreases, gradually reduced
pathoadrenal reactions plays a role, enhancing in- glucose tolerance and diabetes mellitus are formed
sulin resistance (IR) and reducing the production [7; 8; 9].
Objective: To study the characteristics of the blood leptin index in patients with chronic pancreatitis associated with insulin resistance.
Material and research methods
In our work, the object of the study was patients with chronic pancreatitis (CP) associated with the state of IR, who is being treated in the therapy department, RCH No. 1. In the process of research, 58 patients were observed. In accordance with the objectives of the study, 3 observation groups were formed:
1. A group of patients with CP - 40 people.
2. A group of patients with CP associated IR - 18 people.
3. A group of healthy individuals - 14 people.
The average age of patients of all groups
was 52.2 + 2.7 years. In the clinic, an anthropometric examination ofpatients was also carried out - determining the weight and height of patients, determining the circumference of the waist and hips.
Patients with criteria meeting the "Global Consensus on MS criteria" were included in the experimental study group: central obesity, confirmed by a waist circumference of 102 cm for men and 88 cm for women, and any two of the following criteria:
Exclusion criteria for both groups were severe somatic diseases - type 1 diabetes mellitus, chronic renal failure, severe anemia, respiratory failure, and oncological diseases.
The insulin content was determined by enzyme immunoassay (kit company "DRG-Diagnostika" Germany). The leptin content was also investigated with enzyme immunoassay using kits from Diagnostics Biochem Canada). In addition, the study of free
Table 1. - FFA findings in the blood serum
fatty acids (FFA) was performed by the enzymatic method, as an independent predictor of impaired glucose tolerance, IR and diabetes mellitus.
Statistical data processing was performed on the individual computer using the spreadsheet "Microsoft Excel".
Research results and discussion
Based on the obtained research results, it should be noted that along with changes in anthropometric data, carbohydrate and lipid metabolism findings in patients with CP associated with IR there is a change in the functional state of the cardiovascular system. So, in 70% of men and 60% of women, an increase in blood pressure is associated with obesity. For every 4.5 kg of body weight, systolic blood pressure increases by 4.5 mm Hg. An important aspect is the link between obesity and type II diabetes mellitus. Obesity leads to the development of peripheral tissue IR, which plays a trigger role in the development of type II diabetes mellitus.
Deposition of fatty tissue in the abdominal region (or central obesity), as it was found in our patients, was more clearly associated with MS, in particular obesity. Visceral adipose tissue, unlike adipose tissue of different localization, is richer innervated, has a wider network of capillaries and communicates directly with the portal system. Visceral adipocytes have a high density of ft 3 -adreno-corticosteroid and androgen receptors and a relatively low density of a 2 -adrenoreceptors and insulin receptors. These features determine the high sensitivity ofvisceral adipose tissue to the lipolytic effect of catecholamines and low sensitivity to the antilipolytic effect of insulin, especially in the postprandial period.
of the patients with CP associated with IR
Indicator Healthy individuals (n = 14) Group I CP (n = 40) Group II CP with IR (n = 18)
FFA content (mmol/l) 0.28 ± 0.02 0.46 ± 0.04 1.26 ± 0.09*
Note: * - reliability of differences p < 0.05 in comparison with control group
As can be seen from the presented results of the there were no significant changes in the concentra-study (table 1), in the first group of patients (CP), tion of FFA in the blood (0.46 ± 0.04 mmol/L versus
0.28 ± 0.02 mmol/L in healthy individuals). Intensive lipolysis in visceral adipocytes leads to the release of a large amount of FFA, mainly into the portal circulation and liver. In the liver, FFAs inhibit the binding of insulin by hepatocytes, causing the development of IR, a decrease in the extraction of insulin by the liver, and the development of systemic hyper-insulinemia. Once in the systemic circulation, FFA contributes to impaired glucose uptake and its utilization in muscle tissue and, thus, enhance peripheral IR. Excessive content of FFA in the blood serves as a source of accumulation of triglycerides and products of non-oxidative metabolism of FFA in skeletal and cardiac muscles and causes a violation of glucose insulin-dependent utilization in these tissues. Numerous studies in recent years have shown that FFAs have a direct toxic effect on pancreatic ^-cells (the effect of lipotoxicity). The highest values of FFA in the examined individuals were revealed in the group of patients with chronic pancreatitis (CP) combined with IR. So, when comparing the results of a study of the level of FFA with a group of healthy individuals, a more than 4-fold increase was noted (p < 0.001), where its level averaged 1.26 ± 0.09 mmol/L. The intergroup comparison ofpatients ofvarious groups
showed an increase in the level of FFA when compared with group I by 40%, and group II - 2.7 times (p < 0.05).
As mentioned above, in patients with CP combined with IR there was noted hyperglycemia and hy-perinsulinemia. Therefore, high FFA values in patients with a combined form of the disease are apparently associated with impaired insulin receptor function and glucose uptake by cells, which leads to a change in carbohydrate metabolism and the transition of glycolysis to gluconeogenesis, i.e. increased intake of fatty acids and amino acids. A key link in the disorder of lipid metabolism in patients with CP combined with IR is a compensatory hyperinsulinemia, which leads to impaired insulin-mediated utilization ofglucose by cells, which is accompanied by the accumulation of FFA, especially in patients of group II. Therefore, IR in patients with CP affects adipose tissue, enhancing the lipolytic effect of insulin - which leads to the accumulation of FFA and glycerol. In this situation, FFA enters the liver, where it becomes the main source of the formation of atherogenic very low density lipoproteins (VLDL) and triglycerides (TG).
The next stage of our researches was the study of the level of leptin in the blood of subjects.
Table 2.- Indicators of blood leptin in patients with CP combined with IR (M ± m)
Indicator 3 healthy individuals (control) (n=14) Patients CP (n=40) Patients CP combined with (n=18)
Leptin, ng/ml 13.94 ± 0.75 20.42 ± 1.46* 33.68 ± 1.74**
Note: * - reliability of differences p<0,05 in relation
As it can be seen from the presented research results (table. 2), the concentration of leptin is increased in patients suffering from IR. The elevated leptin level in such patients can be explained by "leptin resistance" - the inability of leptin to penetrate into the cerebrospinal fluid and further to the binding sites in the hypothalamus, which are responsible for regulating appetite. That is, the main cause of obesity is not a lack of leptin, but disturbance of sensitivity to it. There is a close relationship between hyperleptinemia and IR. Based on the inhibitory
group of control
effect of leptin on the development of obesity, it is believed that normal production of leptin increases in response to an increase in insulin concentration, which inhibits further production and release of insulin by the principle of negative feedback.
Leptin circulates either in the form of a free hormone or in the form bound to specific binding proteins. One of the main proteins is the extracellular part of the leptin receptor (Ob-R), the so-called soluble receptor. The long Ob-R isoform is expressed in the nuclei of the hypothalamus and other types
of cells, including T cells, pancreatic (3-cells and is aptation of the organism to the changing condi-
responsible for leptin clearance. tions of existence.
Findings 2. Measurement of the concentration of leptin
1. The level of leptin reflects not only the in blood serum can be recommended for inclusion
amount of accumulated fat, but also changes in in the algorithm of examination of patients with CP
energy metabolism: with starvation it decreases, combined with IR and can serve as additional mark-
with overeating it rises. This is a signal for the ad- ers of this condition.
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