Association of Polymorphic Variants of TCF7L2 and PPARG Genes with Metabolic Markers in Patients with Early Disorders of Carbohydrate Metabolism.

We performed complex analysis of the association of polymorphic variants rs7903146 of the TCF7L2 gene and rs1801282 of the PPARG gene with metabolic parameters, insulin resistance, and ß-cell function in a group of patients with early signs of carbohydrate metabolism disturbances in a sample of Tyumen citizens. The study group consisted of 64 people (39 women, 25 men) aged 40-70 years. The distribution of frequencies of alleles and genotypes of the polymorphic markers rs7903146 and rs1801282 was analyzed and associations of carriage of major homozygous polymorphisms with various phenotypic traits were identified. Genotyping for polymorphic variants of TCF7L2 and PPARG genes was performed using allele-specific PCR with primers provided by Synthol company. Carriers of homozygotes for allele C of the polymorphic marker rs7903146 significantly differed from other respondents by a higher level of C-peptide, as well as by the presence of associations with waist circumference, elevated level of glycated hemoglobin, and arterial hypertension. Carriers of homozygotes for the allele C of the rs1801282 polymorphism of the PPARG gene differed from the group of carriers of homozygotes for the allele G and the group of heterozygote carriers by higher levels of triglycerides, as well as the presence of associations with waist circumference and the level of glycated hemoglobin.

[The study of abdominal and parietal enteric microbiota in patients with non-alcoholic fatty liver disease].

AIM: To characterize of the features of changes in the cavity and parietal microbiota of the small intestine in patients with non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Fifty four patients with NAFLD at the stage of steatosis and steatohepatitis at the age of 1860 years were examined. The diagnosis was verified by ultrasound of the hepatobiliary system using a SONIX OP analyzer (Canada), FibroMax test data and liver elastography using an AIXPLORER apparatus (France). The degree of steatohepatitis activity was determined by biochemical blood tests for alanine aminotransferase and aspartate aminotransferase on a Huma Star 600 analyzer (Germany). The cavity microbiota of the small intestine was evaluated using a Lactofan2 analyzer of the Association of Medicine and Analytics company (Russia) using hydrogen breath tests with lactulose. The parietal microbiota of the small intestine was examined using an Agilent 7890 gas chromatograph with mass-selective and plasma-ionization detectors (Agilent Technologies, USA). RESULTS: In the study of cavity enteric microbiota in patients with NAFLD, the syndrome of excessive bacterial growth was detected in 68.5% of cases, while it was caused in 48.6% of patients by a violation of the function of the ileocecal valve, in 21.7% by a deficiency of cleavage of lactulose microorganisms and/or slowing down the motility of the digestive tract. When studying the parietal enteral microbiota, the total bacterial load in patients with NAFLD was significantly lower compared with the control group due to a decrease in useful microbiota. At the same time, a decrease in all normal bacterial representatives Bifidobacterium, Lactobacillus and Lactococcus, Eubacterium and Propionibacterium was noted. The content of opportunistic microbiota in patients with NAFLD did not reveal significant changes. CONCLUSION: The syndrome of excessive bacterial growth in patients with NAFLD is associated with a decrease in useful parietal enteral microbiota.

[The value of mucosal small intestine microbiota in digestion and absorption disorders in metabolic syndrome].

AIM: To evaluate the qualitative and quantitative composition of the parietal microbiota of the small intestine (SI) and its significance in the disturbance of the digestive and absorption functions of the small intestine in metabolic syndrome (MS). MATERIALS AND METHODS: 67 patients with metabolic syndrome were examined. In addition to clinical data, a comprehensive study of the digestive and absorption function of SI was carried out using exercise tests with carbohydrates. The compositional characteristics of mucosal SI microbiota in MS patients were determined by gas chromatography mass spectrometry. The relationship of enteric disorders with changes in small intestinal microbiocenosis was assessed by correlation analysis. RESULTS: The majority (82.9%) of patients with metabolic syndrome showed clinical local and general signs of small intestinal lesions. Violations of all stages of the hydrolysis - resorption process were revealed against the background of changes in the quantitative and qualitative composition of the parietal microbiota of the small intestine. In patients with MS, excessive bacterial growth is observed in the small intestine mainly due to conditionally pathogenic microbiota strains, and, in comparison with the control group, there is a significant increase in the growth of aerobes, microscopic fungi and viruses. The relationship between the severity of excess bacterial growth and impaired digestion and absorption in the small intestine in MS. CONCLUSION: The results of our research suggest that the identified changes in the functional state of SI in combination with a violation of mucosal enteral microbiocenosis are an important link in the complex pathogenesis of the MS.

[Enteral failure and metabolic syndrome: Common neurohormonal mechanisms of development, possibilities of their rational therapy]. / Énteral'naia nedostatochnost' i metabolicheskii sindrom: obshchie neirogormonal'nye mekhanizmy razvitiia, vozmozhnosti ikh ratsional'noi terapii.

The paper deals with small bowel (SB) functional disorders in metabolic syndrome (MS). The main components of a cascade of metabolic abnormalities in MS are closely due to SB functional changes. This is associated to some extent with the presence of common neurohormonal mechanisms in the development of enteropathy and MS. The paper gives the physical, laboratory and instrumental methods for identifying SB dysfunctions in patients with MS. Therapy for the latter is of particular interest in the context of SB functional recovery. The authors discuss the possibilities of enteropathy therapy in patients with MS; thus there is not only SB functional recovery, but also improved overall metabolic processes.

[Correction of small bowel function as a new direction for treating patients with metabolic syndrome]. / Korrektsiia narushenii funktsional'nogo sostoianiia tonkoi kishki kak novoe napravlenie lecheniia bol'nykh s metabolicheskim sindromom.

AIM: To provide a rationale for and to evaluate the therapeutic efficiency of the combined use of pancreatic enzymes and actovegin in the combination therapy of patients with metabolic syndrome (MS) on the basis of comprehensive clinical and functional studies of the small bowel (SB). SUBJECTS AND METHODS: In the course of treatment, 120 patients with MS (verified using the diagnostic criteria elaborated by the All-Russian Research Society of Cardiology (2009)) underwent a comprehensive study of SB function: an isolated study of resorptive processes; evaluation of parietal and cavitary digestion, motor-evacuation function. The peripheral blood levels of gastrin, insulin, cortisol, thyroxine and thyrotropin were determined. RESULTS: The combined use of pancreatic enzymes and actovegin has a positive impact on the clinical and functional state of SB, which was manifested as restoration of its hydrolysis and absorption, as well as motor-evacuation function in the patients with MS. The treatment resulted in reductions in the levels of triglycerides from 2.85±0.34 to 1.53±0.18 mmol/l (p<0.01), total cholesterol from 6.08±0.16 to 5.19±0.21 mmol/l (p<0.05), and atherogenic factor from 5.21±0.28 to 2.93±0.34 (p<0.05). Posttreatment HOMA-IR decreased from 4.22±0.8 to 2.12±0.8. There were no substantial changes in insulin levels and insulin resistance index in the patients on standard therapy. CONCLUSION: The combined use of pancreatic enzymes and actovegin is pathogenetically sound in correcting SB dysfunctions and may be one of the most effective directions for the treatment of patients with MS.

[Cholelithiasis as a possible manifestation of systemic digestive diseases].

AIM: To comprehensively study of the function of digestive organs in cholelithiasis (CL). SUBJECTS AND METHODS: Three hundred and seventeen patients with the early (prestone) stage of CL were examined. The latter was verified by ultrasonography (USG) and biochemical bile tests. The patients underwent pH metry and esophagogastroduodenoscopy, followed by histological examination of gastroduodenal mucosa (GDM) biopsy specimens. Manometry was used to evaluate duodenal function. The serum levels of pepsinogen-1 (PG-1), pepsinogen-2 (PG-2), cholecystokinin (CCK), gastrin, cyclic nucleotides (cAMP and cGMP), α1-antitrypsin, insulin, and C-peptide were analyzed by an enzyme immunoassay. Small intestinal function was examined using a set of diagnostic tests. RESULTS: Gallbladder USG revealed biliary sludge in 273 (86.1%) patients. Biochemical examination of bile established a lower cholatocholesterol coefficient in its cystic as well as hepatic portions, suggesting enhanced bile lithogenicity. Manometry of the duodenum showed its hypertension, hypotension, and normotension in 57.6, 24.8, and 17.6% of the CL patients, respectively. There were significant increases in basal gastric body pH and PG-1 and PG-2 levels as compared to the control group. Morphological examination of GDM biopsy specimens revealed chronic superficial gastritis in 61.8% of the patients, chronic atrophic gastritis in 17.4%, and moderate diffuse duodenitis in 18.3%. In 148 (46.7%) patients with CL, the latter was burdened by pancreatic comorbidity. Stress tests using water-soluble starch, sucrose, and glucose demonstrated impairments in various stages of digestion; substantially decreased levels of CCK, gastrin and cyclic nucleotides were observed in the patients with CL compared to the controls. CONCLUSION: Most patients with CL were detected to have digestive organ structural and functional disorders. Moreover, CL may be regarded as a possible manifestation of systemic digestive diseases.

[Motor-evacuatory function of the gastrointestinal tract in metabolic syndrome]. / Sostoyanie motorno-evakuatornoi funktsii zheludochno-kishechnogo trakta pri metabolicheskom sindrome.

AIM: To investigate the motor-evacuatory function of the gastrointestinal tract (GIT) in metabolic syndrome (MS). MATERIAL AND METHODS: Fifty-eight patients with MS were examined. In addition to clinical findings, an integrated study of GIT motor function by peripheral electrogastroenterocolography was used. The specific features of lipid metabolism and hormonal and autonomic status were studied in patients with MS. RESULTS: The local and systemic clinical signs of small bowel lesions were noted in 82.9% of the patients with MS. There were elevated blood lipid levels in the presence of hypomotor dyskinesia of the upper GIT portions in the postprandial period. New pathogenetic trends in the role of hormones and hypersympatheticotonia in impairing the motor function of the small bowel were found in MS. CONCLUSION: The results of our investigations suggest that the found changes in GIT motor function are an important component of the complex pathogenesis of MS.