Mutations with a decrease in the expression and function of the of the ATP-binding cassette genes proteins ABCG5 and ABCG8, as the main sterol efflux transporters, lead to the accumulation of xenosterols in plasma associated with changes in the lipid profile, hyperglycemia and the risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM2). The review presents studies of the role of ABCG5/G8 polymorphisms in CVD and DM2. In several studies, including large–scale ones, the influence of ABCG5/G8 variants (rs4245791, rs41360247 rs4299376, rs11887534, rs7598542, rs78451356, etc.) on the risk of coronary heart disease (CHD) was proved, in others – when confirming the association of the risk of CHD with ABCG5 polymorphism, this status for ABCG8 was denied. Since sterol metabolism disorders observed in individuals with DM2 are probably associated with low insulin sensitivity, many authors confirmed the association of variants rs4299376, rs4148211, rs140231607 and rs6720173 of the ABCG5/G8 with the risk of DM2, but some authors did not find such a connection with DM2 for variants rs4299376, rs11887534 and rs4148217 of the ABCG8. A decrease in ABCG5/G8 mRNA expression was observed in DM2 in experimental animals and in humans; on the contrary, overexpression of ABCG5/G8 in db/db mice restored the sensitivity of the liver to insulin, which led to a decrease in fasting glucose, lipids and improved glucose tolerance. The inconsistency of data on the association of ABCG5/G8 gene polymorphism with the risk of CVD and DM2 may probably be due to inter-population differences, which necessitates further study of the contribution of ABCG5/G8 variants to the risk of these diseases.

A number of human and animal studies have demonstrated that the hyperglycemia-lowering effects of metformin may result from modulation of the gut microbiota population. Metformin changes the Firmicutes/Bacteroidetes ratio and enhances the growth of some bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and reduce the levels of others such as Intestinibacter. Moreover, in the intestine, metformin not only improves glucose absorption, but also promotes the production of short-chain fatty acids (SCFAs), regulates the secretion of the glucose-lowering hormone glucagon-like peptide 1 (GLP‑1) and other intestinal peptides, inhibits the Farnesoid-X-receptor (FXR) and resorption of the bile acid pool, and may reduce intestinal permeability barrier by increasing the expression of mucin and tight junction proteins, modulates the immune response, has an anti-inflammatory effect, etc. Thus, research results indicate that the intestinal microbiota is involved not only in the hypoglycemic effect of metformin in diabetes mellitus type 2, but also in the implementation of its numerous pleiotropic effects.

Аim: to evaluate metabolic risk factors and their impact on quality of life in patients with pancreatic cancer (PC) and in patients with acute or exacerbated chronic pancreatitis.Materials and methods. Forty-five patients with PC (group 1) and 141 patients with acute pancreatitis or exacerbated chronic pancreatitis (group 2) in an observational multicenter clinical cross-sectional uncontrolled study were examined. Clinical, laboratory and instrumental examination of patients and assessment of risk factors (lipid profile, blood plasma glucose, obesity, arterial hypertension) were carried out in accordance with clinical recommendations. Patients completed the SF-36 questionnaire once to assess quality of life at hospital admission before treatment.Results. In group 1, indicators of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) in blood serum (3.7 ± 0.2; 2.2 ± 0.2 and 0.8 ± 0.1 mmol/L) were lower than in group 2 (5.1 ± 0.1; 3.1 ± 0.1 and 1.2 ± 0.1 mmol/L; p < 0.05). Arterial hypertension was more common in group 1 (55.6 %) than in group 2 (34.8 %; p = 0.013). The presence of arterial hypertension increases the chance of having PC by 2.7 times (p < 0.05). Body mass index parameters, including obesity, as well as parameters of triglycerides, and fasting plasma glucose, did not differ between the groups. Logistic regression analysis revealed a direct relationship with PC HDL hypocholesterolemia (Exp B = 4.976; p < 0.001) and arterial hypertension (Exp B = 2.742; p = 0.027) and an inverse relationship — with hypercholesterolemia (Exp B = 0.204; p = 0.002). The chance of having PC was not associated with age, fasting plasma glucose ³ 7.0 mmol/L, obesity. Quality of life indicators were higher in group 1 than in group 2 on four SF-36 scales: bodily pain (68.1 ± 5.1 and 36.8 ± 2.0; p < 0.001), general health (51.1 ± 2.5 and 38.0 ± 1.7 points; p < 0.001), social functioning (74.7 ± 3.0 and 64.5 ± 2.2 points; p = 0.007), role emotional functioning (28.2 ± 5.2 and 12.5 ± 3.1 points; p = 0.007) and in the general domain “physical component of health” (40.2 ± 1.0 and 33.6 ± 0.8 points; p < 0.001). In group 1 with HDL hypocholesterolemia compared with its absence, the indicators of role emotional functioning (22.2 ± 5.1 and 51.9 ± 13.7 points; p = 0.020) were lower, with arterial hypertension compared with its absence — role physical functioning (5.0 ± 4.0 and 25.5 ± 7.5 points; p = 0.036) and role emotional functioning (16.0 ± 5.1 and 43.3 ± 8.8 points; p = 0.007) were lower.Conclusions. In patients with PC arterial hypertension was more common and the levels of total cholesterol, LDL-C and HDL-C were lower than in patients with acute or exacerbated chronic pancreatitis. The chance of having PC is directly associated with HDL hypocholesterolemia, with arterial hypertension, inversely — with hypercholesterolemia, and is not associated with age, fasting plasma glucose ³ 7 mmol/L, or obesity. In patients with PC, quality of life indicators were higher on four SF-36 scales and on the general domain “physical component of health” than in the group with acute or exacerbated chronic pancreatitis. In patients with PC metabolic factors significantly worsened self-assessment of quality of life in terms of role functioning; in patients with acute or exacerbated chronic pancreatitis there was no such association.

Введение. желчнокаменная болезнь (ЖКБ) встречается у 10–20 % населения в экономически развитых странах. ЖКБ связана с несколькими кардиометаболическими факторами риска: ожирением, дислипидемиями, нездоровым питанием и малоподвижным образом жизни [1, 2]. Наличие ЖКБ значительно увеличивает риск сахарного диабета 2 типа (СД2), сердечно-сосудистых заболеваний, включая ИБС и артериальную гипертензию (АГ), что было доказано в нескольких эпидемиологических исследованиях [3–6]. СД приводит к увеличению индекса насыщения желчи и к гипомоторике желчного пузыря изза висцеральной невропатии, ожирения, гиперинсулинемии, резистентности к инсулину, что может способствовать образованию желчных камней [3]. Связь между АГ и ЖКБ основывается, в частности, на активизации эфферентных симпатических механизмов, ренин-ангиотензин-альдостероновой системы с нарушением моторики желудочно-кишечного тракта из-за импульсации от механорецепторов желчного пузыря при его растяжении, что приводит к повышению АД [5]. Однако при изучении связи ЖКБ и Аг показаны противоречивые результаты [3, 7]. Кроме того, мы не нашли исследований ассоциации АГ с ЖКБ в сочетании с СД2.

Introduction. The study of HCV + HBV mixed hepatitis is a serious problem due to the varied and more severe clinical picture compared to mono-infection, as well as the presence of seronegative variants of HBV infection. In addition, mixed infection is characterized by a more rapid progression of the pathological process to cirrhosis of the liver. The frequency of mixed infection detection has been increasing in recent years. Aim of the research. To study the structural and functional characteristics of the liver in mixed infection with HCV + HBV. Materials and methods. A comprehensive clinical and pathomorphological study of HCV + HBV mixed infection was carried out, which included 112 patients with markers of chronic hepatitis C and B. The age of the patients ranged from 16 to 69 years, 68 men and 44 women. In a clinical study, in addition to a detailed study of the anamnesis, blood biochemical parameters were tested: the level of aminotransferases (AlAT and AST), alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP), bilirubin, total protein, albumin, cholesterol, glucose. The system of hemostasis was studied: prothrombin time, prothrombin index; peripheral blood parameters were determined — hemoglobin, erythrocytes, platelets, leukocytes, ESR. Results. With a high activity of the infectious process, a tendency was found to increase in the surface density of the granular cytoplasmic reticulum in comparison with low activity indicators, which led to rather high ratio of organelles of the protein-synthesizing compartment and mitochondria to the cytoplasm of hepatocytes. In addition, with a high degree of mixed hepatitis activity, a slightly higher structural density of lipid inclusions and a lower volumetric density of cytoplasm devastation zones were found. In general, most of the main cytoplasmic organelles of hepatocytes in chronic HCV + HBV mixed infection had similar indicators of structural density, regardless of the process activity. Conclusion. Mixed HCV + HBV infection is characterized by phenotypic heterogeneity of the hepatocyte population associated with a variety of cytopathic effects caused by complex viral exposure. Hepatitis C RNA virus attacks predominantly cytoplasmic organelles while preserving the nucleus, hepatitis B DNA virus causes degradation of the nuclear compartment with the formation of a ring-shaped nucle cricoid that can be detected by light-optics. The combination of RNA and DNA hepatitis C and B viruses caused phenotypic heterogeneity of the hepatocyte population. Hepatitis C RNA virus caused the degradation of the cytoplasmic compartment of the cell, hepatitis B DNA virus, first of all, caused the modification of the nucleus.

BACKGROUND: In the XXI century, the frequency of pancreas diseases increased 2–3 times. The expectation that causes a pandemic lead to the development of a number of diseases. The results of studies on the relationship of overweight, obesity with the risk of developing pancreas diseases (acute pancreatitis (AP), chronic pancreatitis (CP) and pancreas cancer (PC)) are very heterogeneous (for AP and PC) and not numerous (for CP). AIMS: to identify the frequency of obesity in AP patients (APр), CP patients (СPр) and PC patients (PCр) and compare these parameters. MATERIALS AND METHODS: at the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: the frequency of obesity in APp, CPp; PCp. RESULTS: The frequency of obesity in APp (13,6%), CPp (24,7%) and PCp (20,0%) did not differ significantly. Among the examined patients, the lowest average BMI (24,2±0,7 kg/m 2 ) was observed in APp (p=0,049). BMI ≥22,5 kg/m 2 was found to be associated with AP (OR=0,398; 95%CI 0,195–0,812; p=0,011). An inverse relationship was shown between the BMI and “definite” CP (Exp (B)=0,772; 95%CI 0,632–0,942; p=0,011). In men with CP and in CPp alcoholic etiology, weight deficit was observed significantly more often than in women with CP and in CPp biliary etiology, respectively. Earlier (a year before the present survey), obesity was more common in PCp (55,6%) than in APp (13,6%, χ 2 =3,3; p=0,000) and CPp (25,8%, χ 2 =12,0; p=0,001). A history of obesity (in our study one year before PC detection) and PC (OR=4,435; 95% CI 2,180–9,025; p=0,000) direct relationship was shown. CONCLUSIONS: the frequency of obesity in APp, CPp and PCp was similar. The average BMI was higher in APp, than in CPp and PCp. BMI≥22,5 kg/m2 was a protective factor for AP. BMI was inversely associated with “defined” CP. A history of obesity was directly associated with PC.

BACKGROUND: In the XXI century, the frequency of pancreas diseases increased 23 times. The expectation that causes a pandemic lead to the development of a number of diseases. The results of studies on the relationship of overweight, obesity with the risk of developing pancreas diseases (acute pancreatitis (AP), chronic pancreatitis (CP) and pancreas cancer (PC)) are very heterogeneous (for AP and PC) and not numerous (for CP). AIMS: to identify the frequency of obesity in AP patients (APр), CP patients (СPр) and PC patients (PCр) and compare these parameters. MATERIALS AND METHODS: at the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: the frequency of obesity in APp, CPp; PCp. RESULTS: The frequency of obesity in APp (13,6%), CPp (24,7%) and PCp (20,0%) did not differ significantly. Among the examined patients, the lowest average BMI (24,20,7 kg/m2) was observed in APp (p=0,049). BMI 22,5 kg/m2 was found to be associated with AP (OR=0,398; 95%CI 0,1950,812; p=0,011). An inverse relationship was shown between the BMI and definite CP (Exp (B)=0,772; 95%CI 0,6320,942; p=0,011). In men with CP and in CPp alcoholic etiology, weight deficit was observed significantly more often than in women with CP and in CPp biliary etiology, respectively. Earlier (a year before the present survey), obesity was more common in PCp (55,6%) than in APp (13,6%, 2=3,3; p=0,000) and CPp (25,8%, 2=12,0; p=0,001). A history of obesity (in our study one year before PC detection) and PC (OR=4,435; 95% CI 2,1809,025; p=0,000) direct relationship was shown. CONCLUSIONS: the frequency of obesity in APp, CPp and PCp was similar. The average BMI was higher in APp, than in CPp and PCp. BMI22,5 kg/m2 was a protective factor for AP. BMI was inversely associated with defined CP. A history of obesity was directly associated with PC.

Aim. To determine the prevalence of hypertension (HTN) in patients with acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC) and establish associations of HTN with other risk factors (obesity, dyslipidemia (DLP), plasma glucose ≥7,0 mmol/l, smoking, alcohol consumption).Material and methods. This observational multicenter clinical cross-sectional uncontrolled study included 44 patients with AP, 97 patients with CP and 45 patients with PC. The groups were comparable by sex and age. The HTN was diagnosed according to the criteria of Russian Society of Cardiology (2020).Results. HTN was much more common in patients with PC (55,6%) than in patients with AP (25,0%) (χ 2 =8,6, p=0,003). In patients with CP, the prevalence of HTN (39,2%) did not differ from those with AP or PC. Among patients with AP and HTN, higher levels of triglycerides (TG) (U=88,0, p=0,010) and glucose (U=89,5, p=0,011) than in non-HTN patients with AP were determined. In HTN patients with CP, glucose ≥7,0 mmol/l was recorded 3 times more often than in non-HTN patients with CP (χ 2 =16,2, p=0,000). In patients with PC and HTN, a higher mean body mass index (BMI) (F=7,8, p=0,008) and less common normal body weight than in non-HTN patients with PC (28,0 and 65,0%, χ 2 =6,2, p=0,013) was revealed. In patients with CP, increased glucose levels by 1 mmol/l (Exp (B)=1,933, 95% confidence interval (CI) 1,350-2,767, p=0,000) or BMI by 1 kg/m2 (Exp (B)=1,224, 95% CI 1,085-1,380, p=0,001) raised the probability of HTN; in patients with PC, increased BMI by 1 kg/ m2 (Exp (B)=1,394, 95% CI 1,057-1,840, p=0,019) or age by 1 year (Exp (B)=1,251, 95% CI 1,052-1,489, p=0,011) raised the probability of HTN.Conclusion. HTN was more often observed in patients with PC than in those with AP. In patients with CP, the prevalence of HTN did not differ from those with AP or PC. HTN was a cofactor to other metabolic risk factors (glucose ≥7,0 mmol/l, obesity) in patients with AP or CP; behavioral risk factors, on the contrary, were less common in HTN patients with AP or CP. In patients with CP, there was a direct association of HTN with glucose levels or BMI, and in patients with PC — HTN with BMI or age.

The prevalence of metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreatic disease (NAFPD) is 1/4–1/3 of the planet population. It has been proven that the main links in their pathogenesis are disorders of lipid and carbohydrate metabolism. A high comorbidity of NAFLD and NAFPD was shown: in 67,9 % of patients with NAFPD, fatty liver was revealed, and in 96,8 % of patients with NAFLD, pancreatic steatosis was diagnosed. The prevalence of MC among NAFPD patients is 59,2–76,9 %. A meta-analysis revealed that NAFPD is associated with an increased risk of MS (relative risk (RR) = 2,25; 95 % CI 2,00–2,53; p < 0,0001), arterial hypertension (RR = 1,43; 95 % CI 1,08–1,90; p = 0,013), NAFLD (RR = 2,49; 95 % CI 2,06–3,02; p < 0,0001), diabetes mellitus 2 type (RR = 1,99; 95 % CI 1,18–3,35; p = 0,01), and obesity (RR = 1,91; 95 % CI 1,67–2,19; p < 0,0001). Concomitant MS negatively affects the clinical course of acute and chronic pancreatitis, for example, moderately severe acute pancreatitis is observed 3 times more often with MS than without MS, partly due to that I, IV and V types of hyperlipidemia are associated with acute pancreatitis. Dyslipidemia in NAFLD occurs in 60–70 % of cases and is characterized by hypertriglyceridemia, elevated level of free fatty acids and low density lipoprotein cholesterol, decreased content of high density lipoprotein cholesterol. Therefore, strategies aimed at the primary prevention of dyslipidemia can help reduce morbidity and mortality in liver and pancreatic pathology associated with MS.

The aim is to identify the characteristics of nutrition and their relationship with gastrointestinal symptoms in women with Gallstone Disease (GSD) with metabolic syndrome (MS). The open clinical study “series of cases” included 97 patients with GSD: group 1 - GSD with MS (n=67), group 2 - with GSD without MS (n=30), comparable in age and BMI. Criteria for MS - NCEP ATP-III, 2001. A nutritional frequency questionnaire validated at the Institute of Nutrition RAS was used. Results. In group 1, significantly less vegetable proteins (22.6 ± 1.2) and fats (29.7 ± 2.0), total carbohydrates (161.6 ± 8.5), and sugar (74.1 ± 4,5) and fibers (27.9 ± 1.7 g/day) than in group 2 (26.2 ± 1.7, 38.8 ± 3.7, 194.7 ± 15.6, 107.3 ± 12.2, 43.1 ± 6.4 g/day, respectively). In group 1, significantly more animal proteins (56.8 ± 2.4 g/day) and cholesterol (223.6 ± 12.0 mg/day) were consumed than in group 2 (45.5 ± 3.2 g/day and 188.8 ± 21.6 mg/day, p<0.05). Association between the animal fats and proteins consumption with pain and dyspeptic symptoms was stronger in group 1 than in group 2. Conclusion. Women with GSD and MS consumed less vegetable foods and more animal food, which were accompanied by an increase in gastrointestinal symptoms of gallstones.

Nonalcoholic fatty pancreatic disease (NAFPD) integrates the spectrum of chronic clinical and morphological pancreatic changes: steatosis and nonalcoholic steatopancreatitis. NAFPD prevalence in USA was 27.8%, in China--12.9-16%. According to our data, 51.8% of patients with chronic pancreatitis was diagnosed MS. Association NAFPD with MS has been confirmed in most studies, the presence of any components of MS increases the prevalence NAFPD by 37 %. In the NAFPD pathogenesis is important not only excessive intake of free fatty acids (FFA), which leads to the pancreatic parenchyma inflammation and fibrosis, but also "glucolipotoxicity" (i.e., the combined toxicity of hyperglycemia and increased FFA level) for β-cells. It is shown that NAFPD is an initial index ofectopic fat deposition, and the earlier manifestation of MS than NAFLD. Most likely, a stage (or degree) of the MS is usefully to determine as the pancreatic status--its exo- and endocrine functions, and fat deposition. This approach will allow us to develop new therapeutic approaches not only to treatment but also to the primary prevention of metabolic syndrome.

The purpose of the review--to analyze the basic data on modifiable and genetic risk factors of pancreatic cancer (PC). PC is the most fatal disease that kills about 95% of patients. Among the known risk factors for PC only for smoking, obesity, and family history a positive association with the PC risk in meta-analyzes confirmed. The PC etiology remains unclear, more than 90% of patients acquire it sporadically. Currently, the most significant genes for PC include KRAS2, p16/CDKN2, TP53, SMAD4/DPC4. Mutations in the KRAS noted in 90% of cases of pancreatic ducts adenocarcinoma. p16/CDKN2A mutation is accompanied by a 38-fold increased risk of PC compared with the general population. TP53 mutations are associated not only with carcinogenesis but also PC metastasis, as well as SMAD4/DPC4 mutations. Study of the role of genetic aspects in the PC development is necessary both to identify individuals with high PC risk, as well as for the development of gene-specific treatments, such as inhibitors of proteins, histone deacetylase, and histone acetyltransferase (vorinostat, belinostat, entinostat, panobinostat, curcumin) are in clinical trials.

THE PURPOSE OF THE REVIEW: Analyze the basic data on the role of obesity in the pathogenesis of pancreatic cancer (PC) and the modern mechanisms of this association.RECENT LITERATURE DATA:In the European Union and in Russia incidence of pancreatic diseases increases, such pancreatic cancer (PC) ranks 10th among cancer diseases. Obesity is a risk factor for not only of severe acute pancreatitis, but also PC at that independently of diabetes. In a meta-analysis the PC risk in obese increased by 47%, while the person with a central obesity have a higher PC risk compared to those with a peripheral type of obesity (odds ratio = 1,45, 95% CI: 1,02-2,07), but association between BMI and PC risk in this Japanese population may be different from that in Western populations, sometimes inversely. The link between obesity and PC is explained by insulin resistance and hyperinsulinemia: was proved a direct correlation between the level of circulating C-peptide and PC, low levels of serum adiponektin and leptin increase the PC risk. There are also genetic risk factors for PC: a statistically significant interaction between IVS1-27777C> and IVS1-23525A>T genotypes of the FTO gene with obesity and the PC risk: AA genotype in patients with BMI < 25 kg/m2 reduced PC risk by 22%-28% (p < 0,0001), and with BMI ≥ 25 kg/m2 was associated with 54%-60% increased PC risk (p < 0,0015). Lifestyle factors (smoking, consumption of saturated fats, etc.) increase the PC risk.

AIM:To study vessel-platelet and coagulation parts of hemostasis system, their correlation with clinical characteristics and activity of chronic tubulointerstitial nephritis (CTIN).MATERIAL AND METHODS:128 patients 15 to 65 years of age with CTIN were included in the study. The diagnosis was confirmed morphologically in 42 patients. The patients were divided into subgroups by activity of the disease at the moment of examination (active and inactive CTIN), by arterial pressure (normotensive and hypertensive patients), intact and low renal function, by duration of the disease (up to 60 months, 61-120 months, more than 120 months). Complex study of hemostasis system was carried out by a set of standard techniques.RESULTS:CTIN runs with activation of vessel-platelet hemostasis characterised by a decrease in platelets count (p < 0.001), persistent platelet hyperaggregation and activation (p < 0.001). Severity of platelet aggregative activity is related with endothelial affection manifesting with high level and activity of Willebrand factor (p < 0.001). The most typical changes of coagulation in CTIN were acceleration of activated partial thrombin time (p < 0.001) closely related with activation of thrombocytic hemostasis and background thrombinemia the presence of which was confirmed by elevated blood level of soluble fibrin-monomeric complexes (SFMC).THE CONCLUSION:Hypercoagulation, suppression of fibrinolytic plasma activity, increase of SFMC and fibrinogen levels in the blood as well as detected enhancement of platelet aggregation testify to a latent course of renal intravascular blood coagulation in CTIN. Hemostasis system activation in CTIN helps assessment of the disease activity.