Beneficial effect of bariatric surgery is expressed not only in reducing body weight, but also in improving the functioning of the body as a whole. On the one hand, numerous studies devoted to the investigations of specific mechanisms of the influence of bariatric surgery on the general condition of an organism testify to the enormous interest of scientists in this problem. On the other hand, the range of changes is so vast that it covers almost all physiological and biochemical processes. The most noticeable response to bariatric surgery is from the digestive (including the composition of the microbiota), immune (reducing the level of systemic and local inflammation), cardiovascular (reducing the risks of atherosclerosis and other diseases) systems. Partial or complete compensation of type 2 diabetes mellitus and metabolic syndrome also occurs. Among the variety of data, there is insufficient research on only standard biomarkers: leptin, C-reactive protein, interleukin 6, etc. A detailed study of the profiles of both circulating biomarkers and local ones is necessary. At the same time, it is obligate to continue to accumulate evidence on the positive effect of bariatric surgery, since this type of surgical intervention has come into practice relatively recently. Unfortunately, at the present time in Russia bariatric surgery is not an affordable and popular treatment for morbid obesity (MO). Nevertheless, it is extremely important to change the current situation, since bariatric treatment is an optimal and effective solution to socially significant diseases such as MO or type 2 diabetes mellitus.

Recently, the world literature has been actively discussing the effect of circadian rhythm and sleep disturbances on human metabolic health. One of the most socially significant causes of circadian disorders is the shift work schedule. Shift work schedules began to occur more often due to the high demand for flexibility and labor productivity in modern society. Shift work is characteristic of medical personnel, law enforcement officials, rescue services, transport, the media and others. Shift workers make up about 17% of all workers in Europe. Globally, approximately 2.5 billion people work in shifts. Shift work was identified as an important professional risk. The connection between work with rotation of day and night shifts with overweight and obesity, with circadian rhythms and sleep disorders was proved. The review systematizes information regarding the role of the shift chart in the development of obesity and the metabolic syndrome, and considers mechanisms that mediate its effect on the regulation of energy balance.

Obesity is a recurring polyetiological disease. Overweight are 30–60% of women of reproductive age, and 25–27% are obese. By 2025, it is expected that 50% of women on our planet will be obese. Obesity in women of reproductive age is accompanied by a high frequency of anovulation, hyperandrogenism, menstrual irregularities, endometrial pathology, infertility. During pregnancy, this group of women has a higher risk of short term loss, including pregnancy in the outcome of assisted reproductive technologies. Weight gain and obesity can lead to decreased fertility in women. The body mass index of a woman of reproductive age negatively affects the course of pregnancy, namely: the risk of gestational diabetes, increased blood pressure, eclampsia, the pathological course of the birth act and the pathology of the newborn increase. Obesity in women of reproductive age is an independent risk factor for cancer: breast cancer and endometrial cancer, and also leads to a decrease in the survival rate for ovarian cancer. Obesity often accompanies polycystic ovary syndrome, which occurs in every 10th patient of reproductive age. The combination of these diseases increases the risk of cardiometabolic conditions such as impaired glucose tolerance, type 2 diabetes and dyslipidemia. Weight loss in these patients is a necessary component of complex therapy aimed at improving reproductive potential.

Obesity may present as a significant medical problem for any person, regardless of age or gender. In men obesity causes considerable psychological stress, sexual dysfunction, subfertility, hypogonadism and cardiovascular conditions. These problems may form numerous pathological associations between each other, creating a vicious circle. The main factors which influence male fertility and sexual function in obesity and metabolic syndrome are imbalance of sex hormones and systemic inflammation. In many patients symptomatic treatment is necessary for above-mentioned manifestations, but it is always rational to act on their pathophysiology and to recommend to lower the body mass by diet and lifestyle modification. When it proves impossible for the patient to follow such recommendations and when behavioral approach fails, central-acting and peripheral-acting medications may be used, including orlistat, sibutramine and liraglutide. Bariatric surgery should be offered to patients with high body mass index in whom conservative management fails. Without elimination of excess body mass it is difficult to solve problems regarding sexual dysfunction, hypogonadism and subfertility in obese males. All these issues and available modes of pharmacological treatment are described in this review.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is considered to be the liver manifestation of metabolic syndrome. Currently, there is no etiotropic treatment of NAFLD, so an active research for new methods of treatment is underway. In the meantime, drugs are used to treat comorbid conditions, such as dyslipidemia, arterial hypertension, obesity, type 2 diabetes, which are present in varying degrees in patients. This review considers medications that are used in patients with NAFLD and related concomitant features, and also describes new strategies for regressing changes in liver tissue in NAFLD. In our opinion, one of the promising groups of drugs are agonists of the farnesoid X receptor (FXR). FXR belongs to the group of nuclear receptors, which are ligand-activated transcription factors that regulate the genes involved in metabolism. FXR agonists can claim to be a new promising drug for the treatment of NAFLD and related diseases influencing carbohydrate metabolism, fat metabolism, bile acid metabolism, as well as inflammatory processes in the liver to ensure metabolic homeostasis.

BACKGROUND: Metabolic syndrome and obesity are often precursors of type 2 diabetes mellitus (DM), and current recommendations indicate the advisability of early initiation of drug therapy at the stage of prediabetes. Drugs with incretin activity are one of the priority groups for monotherapy of type 2 diabetes in the onset of the disease, and certain drugs are used to treat obesity. GPR119 agonists increase the secretion of endogenous incretins, and their effectiveness in the treatment of type 2 diabetes and obesity in mono- and combination therapy is currently being actively studied.

AIM. To evaluate of the effect of administration of a GPR119 receptor agonist, its combination with metformin or sitagliptin on body weight, food intake and glycemia in rats under a high-calorie diet.

MATERIALS AND METHODS: The study was conducted on 56 outbred female rats aged 7–8 months and an initial weight of 305–320 g. Compound ZB-16 is a highly active GPR119 receptor agonist (EC50 = 7 nM). For 12 weeks, the animals were kept on a high-fat and carbohydrate diet and at the same time received the compound ZB-16, metformin and sitagliptin, or its combination (ZB-16 + metformin and ZB-16 + sitagliptin). During the experiment, the weight of the animals, the mass of feed eaten, as well as the level of glycemia after 6 hours of fasting and with an oral glucose load were assessed.

RESULTS: In animals of the control group that were on a high-calorie and fatty diet for 12 weeks, an increase in body weight, glycemia and a decrease in the rate of glucose utilization were observed. The introduction of the GPR119 agonist (ZB-16) for 12 weeks led to a significant reduction in the amount of food consumed, limited weight gain and prevented the development of carbohydrate metabolism disorders. The addition of sitagliptin and especially metformin to therapy with the GPR119 agonist significantly increased the effectiveness of therapy compared to the control group, which was expressed in the normalization of animal body weight and glycemia (p <0.05).

CONCLUSIONS: The introduction of a combination of the GPR119 agonist (compound ZB-16) with metformin and sitagliptin is more effective than monotherapy in terms of weight gain, food intake, and also prevents the development of carbohydrate metabolism disorders in animals when kept on a high-fat and carbohydrate diet.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is associated with impaired glucose metabolism and peripheral insulin resistance, which is accompanied by an high risk of cardiovascular disease (CVD) and nephropathy. Metabolic syndrome and T2DM are accompanied by renin-angiotensin system (RAS) activation, which is also associated with increased risk of CVD and kidney damage. Obesity lead to a wide range of pathophysiological changes, that stimulate cardiac fibrosis, and various fibrosis processes initiation, including activation of transforming growth factor β (TGF-β).

AIMS: To determine activity of angiotensin II (Ang II) and TGF-β in patients with obesity and T2DM and their association with heart and kidney damage.

MATERIALS AND METHODS: Ang II and TGF-β were identified in the peripheral blood of 66 obese patients aged 48-65 years. The first group included 21 patients with coronary heart disease (CHD) and T2DM; The second group included 22 patients with T2DM and excluded CHD; The third group – 20 patients with normal glucose metabolism and excluded CHD.

RESULTS: The values of TGF-β in the 1st group (patients with CHD) were statistically lower than in the group of metabolically healthy obesity (p=0.021). Patients who received DPP-4 inhibitors had a lower Ang II level compared to patients with other hypoglycemic therapy (p=0.005). TGF-β positively correlated with glomerular filtration rate (eGFR) in all patients (r=-0.414, p=0.006). TGF-β negatively correlated with the degree of internal carotid artery stenosis in patients of the 2nd group (r=-0.42, p=0.09) and LDL-cholesterol in all patients (r=-0.426, p=0.038).

CONCLUSIONS: TGF-β negatively correlated with the factors that contribute to CVD progression. TGF-β correlated with pathological angiogenesis and changes in normal cardiac geometry in obesity, T2DM and CHD. DPP-4 inhibitors can improve the cardiovascular prognosis in this group of patients by affecting Ang II level. Low levels of TGF-β were associated with higher cardiovascular risk and were commonly found in patients with more severe nephropathy.

BACKGROUND: The relevance of the problem of obesity today is not in doubt. One of the most effective treatments today is bariatric surgery. At the same time, the effectiveness of the surgical method is not always predictable, as it is influenced by various factors, including the psychological state of the patient.

AIM: To study the psychological characteristics of patients with obesity before and after surgical (bariatric) treatment and to establish the relationship with weight loss.

MATERIALS AND METHOD: The study involved 32 patients with morbid obesity before and a year after laparoscopic longitudinal resection of the stomach with an initial body mass index of 45.36 (+54.90; -33.00). Questionnaire used: Symptom Check List-90-R (L.R. Derogatis). Statistical data processing was carried out using the statistical programming language R.

RESULTS: The presence or increase in the level of phobic anxiety (a persistent reaction of fear to certain people, situations and places) and psychotism (isolation, interpersonal isolation, avoidance) in a patient can have a negative impact on the success of weight loss in the postoperative period.

CONCLUSIONS. The psychological factors affecting the prognosis of weight loss after bariatric surgery have been identified. Psychological testing and determining the patient’s psychotype can be predictive in improving the outcome of surgical treatment of obesity.

BACKGROUND: One of the consequences of obesity for the female body is a decrease in fertility. It is shown that impaired reproductive function in obese patients can be associated, in particular, with a decrease in ovarian reserve.

AIMS: To evaluate the ovarian reserve function in female patients of reproductive age with different classes of obesity in comparison with women without obesity.

MATERIALS AND METHODS: This study evaluated 320 caucasian women, age 20-30 years, without obesity (BMI<30, n=80) and with obesity WHO class I-III (n=80 per class). Anthropometrics, serum concentrations of anti-Mullerian hormone (AMH), inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and testosterone were compared on the 2-3 day of menstrual cycle as ovarian volume and antral follicle count (AFC).

RESULTS: We reveal statistically significant difference in following parameters in normal BMI women in comparison with obesity women: AMH, testosterone, ovarian volume and AFC. Moreover, we reveal significant difference between patients with different WHO class of obesity. But even in class III obesity parameters remained within reference ranges.

CONCLUSIONS: Ovarian reserve function parameters progressively decrease with increase of obesity class in subjects, but ovarian reserve parameters were in normal reference range even in class III obese patients. Further large randomized multicenter studies are required to find influence of obesity in relation to ethnicity and other factors to ovarian reserve function.

BACKGROUND: Considering the negative influence of a visceral obesity on spermatogenesis, it is important to investigate its pathogenetic factors.

AIMS: To reveal the pathogenetic factors of disorders in spermatogenesis and antioxidative activity of an ejaculate in young men with post pubertal visceral obesity and normal andrological anamnesis.

MATERIALS AND METHODS: 47 men under 30 years with post pubertal and nutritional visceral obesity have been included into one-stage research. The length of circle of waist, lipid blood spectrum, blood levels of glucose and insulin, antioxidant activity and electronic-microscopic analysis of an ejaculate have been examined. Differences were considered statistically significant with p <0,05.

RESULTS: The LDL and triglyceride levels in patients with disorders in spermatogenesis were significantly higher than considered in men with normozoospermia. Correlations between antioxidative activity of ejaculate and levels of LDL (n=47, r=-0,310; p=0,033), triglyceride (n=47, r=-0,366; p=0,011) and the number of normal spermatozoons in ejaculate (n=47, r=0,343;p=0,017) have been revealed.

CONCLUSIONS: The dyslipidemia in young men with post pubertal visceral obesity and normal andrological anamnesis can be considered as pathogenetic factors of disorders in spermatogenesis. Nevertheless the dyslipidemia can influence spermatogenesis through oxidative stress.

BACKGROUND: Vitamin D binding protein is a main vitamin D carrier in serum. It also has an impact on macrophagial function. Role of vitamin D and macrophages in the pathogenesis of atherosclerosis is scientifically proven but there is lack of data on vitamin D binding protein in this regard.

AIMS: To evaluate the vitamin D binding protein polymorphism in patients with acute coronary syndrome without diabetes mellitus, autoimmune diseases and malignant tumors. Determine correlation, if there is, between vitamin D binding protein allele and features of acute coronary syndrome among this patient group.

MATERIALS AND METHODS: It is a cross-sectional observational study. Study subjects are patients with acute coronary syndrome. Exclusion criteria are the presence of diabetes mellitus, autoimmune diseases and malignant tumors. In all participants were evaluated: predisposing factors for heart diseases, CBC, biochemical blood test, troponin, coronarography, echocardiography. The study lasted for 5 months from November 2017 until March 2018. Primary end point – assessment of vitamin D binding protein polymorphysm in this group of patients with acute coronary syndrome by means of vitamin D binding protein gene sequencing. 50 patients were enrolled into this study who were urgently admitted to hospital and diagnosed with acute coronary syndrome. Among them – 36 males and 14 females. Mean age was 60 (55;66) years. All participants were sequenced for single nucleotide polymorphysm in VDBP p.T436K (rs4588) and P.432E (rs7041).

RESULTS: Gene polymorphysms of interest were found in 43 patients among 50 enrolled. Haplotype Gc1s/2 (rs7041G-rs4588A) was found in 7 (14%) patients, Gc2 (rs7041T-rs4588A) — in 9 (18%) patients, Gc1s (rs7041G-rs4588C) – in 20 (40%) patients, Gc1f (rs7041T-rs4588C) in 14 (28%). Coronarography showed that coronary artery occlusions obstructing more than 50% of vessel lumen was found in 16 patients; obstruction greater than 90% was seen in 8 patients; total occlusion – in 4 patients.

CONCLUSIONS: In patient group with acute coronary syndrome prevalence of vitamin D binding protein gene polymorphysm was high – in 86% of participants. The features of Gc2 haplotype were higher frequency of recurrent myocardial infarction and total coronary artery occlusion, as well as tendency to decreased serum vitamin D3 (25(OH)D) levels.

BACKGROUND: The subject of discussion is the issue of the separation point, which determines sufficient levels of vitamin D for bone health. When determining the adequate reference range of vitamin D, researchers are mainly guided by the results of research, where the level of 25(OH)D is determined, at which the PTH level decreases and reaches a plateau.

AIM: To establish the «cut-off point» of vitamin D by suppressing excessive secretion of PTH.

MATERIALS AND METHODS: Observational, single-site, single-stage, selective, uncontrolled study of the search for vitamin D levels by the effect on PTH secretion in residents of Tyumen region was conducted (n = 176). All selected study participants determined the level of 25(OH)D and PTH in serum. The calculation of the «cut-off point» was carried out using the method of searching for changes in the correlation dependence of PTH on the level of vitamin D, followed by verification of the data obtained using ROC analysis.

RESULTS: A mathematical analysis of the dependence of 25(OH)D and PTH showed the “cut-off point” of vitamin D, equal to – 23.6 ng/ml.

CONCLUSION: The “cut-off point” of 23.6 ng/ml is optimal for suppressing excessive PTH secretion. The data obtained may be an incentive for further working out the “cut-off point” of vitamin D for the Russian population and can be used to clarify the classification of deficiency, insufficiency and optimal levels of vitamin D for the population of the Russian Federation.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a widespread endocrine disease characterized by excessive production of parathyroid hormone (PTH) due to parathyroid gland hyperplasia (PGH) or tumor lesions (adenoma or cancer of the parathyroid gland (PG) in 80% and 1–5% of cases respectively). Choline kinase α–alpha (XKα) overexpression is described in tumors of different localization, but there is no data on its expression in PG tumors.

AIMS: To study the character of XKα expression in PG neoplasms and its relationship with clinical, laboratory, and visualization characteristics (positron emission tomography combined with computed tomography (PET/CT) with ¹⁸F–fluorocholine (¹⁸F–FC)).

MATERIALS AND METHODS: The material for the study was based on tissue samples from 10 patients of 34–70 years old (Me = 61.5; [48; 66]), with a laboratory–confirmed diagnosis of PHT. An immunohistochemical study (IHC) was carried out on materials from 2 patients with hyperplasia of the main cells, from 5 patients with adenoma of PG, from 1 patient with atypical adenoma and 1 with carcinoma of PG; in 1 case the metastasis of cancer of the neck with lymph node was examined.

RESULTS: The expression of XKα is spotted in all types of PG cells (chief cells: active and inactive forms), transitional forms between the chief cells and oxyphil; oxyphil cells, but it was most intense in active chief cells. The expression of XKα was observed in neoplasms of PG of various degrees of malignancy. In the most numerous group of PG formations with a favorable prognosis (11 samples from 7 patients), no statistically significant correlation (p> 0.05) was obtained between the intensity expression of the XKα, of the PTH and the proliferative activity index Ki–67, the level of radiopharmaceutical accumulation in PET/CT with ¹⁸F–FC (SUVmax) and laboratory data (PTH, Ca, Ca++).

CONCLUSIONS: In the majority of investigated cases, moderate and intensive expression of the XKα was detected in PG cells. A small amount of studied cases does not allow us to identify the connection between the intensity of XKα expression and the malignant potential for the formation of PG.

Hyperparathyroidism is an endocrine disease characterized by excessive secretion of parathyroid hormone (PTH) by the parathyroid glands. Primary hyperparathyroidism (PHPT) can be diagnosed biochemically with the combination of hypercalcemia and upper-normal or elevated levels of PTH. There are few descriptions of PHPT with normal intact PTH secretion in the literature. The incidence of PHPT among patients with recurrent urolithiasis is 2–8%. We present a clinical case of diagnosing PHPT in a 64-year-old female patient with rare variant of the disease. Before establishing the diagnosis, the main patient complaints were long-term recurrent nephrolithiasis and nephrocalcinosis. Surgical treatment made it possible to achieve rapid normalization of biochemical parameters of calcium-phosphorus metabolism, increase bone mineral density in the lumbar spine, improve the general condition of the patient. This clinical case demonstrates errors and late diagnosis of PHPT associated with poor knowledge of the manifestations of hyperparathyroidism and its masks. The authors recommend to determine the concentrations of total calcium, albumin, serum levels of PTH in patients with clinical picture of PHPT, in order to exclude the disease.