Khomenko M. The role of gastrointestinal peptides and the state of intestinal microecology in the formation of hepatobiliary pathology in obese adolescents

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0822U100362

Applicant for

Specialization

  • 228 - Педіатрія

30-12-2021

Specialized Academic Board

ДФ 64.609.032

The Kharkiv Medical Academy of Postgraduate Education

Essay

There is a steady increase in the prevalence of childhood obesity globally, often accompanied by the development of associated diseases that were previously considered to be unique to the adult population. Among the most common pathologies associated with obesity are diseases of the hepatobiliary system, namely non-alcoholic fatty liver disease, which occupies one of the main places. Recent studies suggest that the pathogenesis of obesity and non-alcoholic fatty liver disease is complex and multifactorial. Particular attention is paid to the close two-way relationship between intestinal and liver processes due to many factors, including the state of the intestinal microbiota. In addition, recent studies emphasize the vital role of the gastrointestinal tract as one of the largest hormone-producing organs in the human body, and gastrointestinal hormones are considered as part of a single system of energy balance regulation in which these compounds affect body weight, nutrition, and insulin resistance, thus, contribute to the pathogenesis of both obesity and non-alcoholic fatty liver disease. The study aimed to determine the role of gastrointestinal peptides, the state of intestinal microbiota and intestinal permeability, a marker of apoptosis of hepatocytes, cytokines, endogenous intoxication in the formation of hepatobiliary pathology in obese adolescents. To achieve the goal and the objectives of the study, we conducted a comprehensive survey of 108 obese adolescents aged 12 to 18 years (mean age – 14,59 ± 1,61), including 55 (51,0) % of boys and 53 (49,0) % of girls. According to the study results, all children with obesity were diagnosed with functional disorders of the biliary tract (FDBT) in the form of functional disorders of the gallbladder by hypokinetic type, and in 79 children - non-alcoholic fatty liver disease (NAFLD). With this in mind, the surveyed adolescents were divided into two groups: 1st group - obese adolescents and FDBT, 2nd group - obese adolescents and NAFLD. The control group included 32 adolescents of the same age group with normal body weight (from the 5th to the 85th percentile) with no signs of acute and chronic disorders, including 18 (56, 2) % of boys and 14 (43, 8) % of girls 12 - 18 years (mean age – 14,96 ± 1,83). All patients underwent a comprehensive clinical and anamnestic examination, clinical and biochemical blood tests, ultrasound (US) examination of the abdominal cavity, determination of immunoreactive insulin (IRI), ghrelin, glucagon-like peptide-1 (GLP-1), cytokeratin-18 (CK-18), zonulin, lipopolysaccharide (LPS), interleukin-6 (IL-6) and interleukin-10 (IL-10), serotonin, microbiological examination of feces, and examination of violations of eating behavior (EB) according to the DEBQ questionnaire. According to clinical and anamnestic data, no statistically significant differences were found in obese adolescents with FDBT and NAFLD groups. Anthropometric indicators such as body weight, body mass index (BMI), waist circumference (WC), hip circumference were significantly higher only in obese girls with NAFLD compared to the group of obese girls with FDBT (p < 0,01), WC / height, which characterizes the severity of the abdominal type of fat distribution, was higher in both girls and boys in the group of patients with NAFLD, compared with patients with FDBT. Increases in liver size were significantly more common in obese adolescents with NAFLD than in obese adolescents with FDBT (p < 0,05). Assessment of EB showed that significantly more often, violations of EB were detected in adolescents with obesity, compared with the control group - in 90,1% and 34,4%, respectively (p < 0,001). In addition, the frequency and severity of the restrictive type of violation of EB in obese adolescents were statistically significantly higher than the control group (p < 0,001), regardless of the surveyed groups. The analysis of biochemical parameters revealed that in obese adolescents, the concentration of glucose and IRI was significantly higher in obese adolescents with NAFLD compared with obese adolescents with FDBT (p < 0,05, p < 0,01, respectively). The incidence of insulin resistance (IR) and its expression according to the HOMA-IR index were higher in the group of obese adolescents with NAFLD compared to obese patients with FDBT (p < 0,01). The mean levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher among obese adolescents with NAFLD compared to obese patients with FDBT (p < 0,05). It was found that the level of ALT, AST and alkaline phosphatase in the group of patients with FDBT and IR was significantly higher than in the same group without IR (p < 0,01, p < 0,05, p < 0,01, respectively). In the group of patients with NAFLD, the level of enzymes did not depend on the presence of IR.

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