Thiazolidinediones are insulin sensitizers – a class of antidiabetic drugs that reducing insulin resistance, convincingly improve glycemic control in patients with type 2 diabetes. In addition to glucose-reducing action, a representative of this class – pioglitazone in studies demonstrates other pleiotropic effects associated with a decrease in blood pressure, a decrease in the level of pro-inflammatory cytokines and prothrombotic factors, correction of dyslipidemia and improving the state of the vascular wall. In accordance with these anti-atherogenic and metabolic effects of pioglitazone in patients with confirmed cardiovascular diseases, he reduced the frequency of development of large atherosclerotic events in prospective randomized clinical studies (studies of PROactive and IRIS), as well as in meta-analyses of all published studies of pioglitazone. Pioglitazone reduces albuminuria and proteinuria, mortality from all causes and cardiovascular events in patients with diabetes and chronic kidney disease. In other studies, the intake of pioglitazone was associated with mobilization of fat from liver in patients with non-alcoholic fatty liver disease with an improvement in its function and a positive effect on fibrosis. This article also provides an analysis of unwanted phenomena that were noted during the study of pioglitazone. The identified weight increase, swelling, bone fractures of the limbs, have a rare frequency of occurrence and dose-dependent nature. Indeed, when using low doses of pioglitazone (7.5–30 mg/day), the ratio of benefit/risk for the drug seems very favorable. At the same time, the benefits of pioglitazone with a significant improvement in cardiovascular and cerebrovascular outcomes are higher with secondary than with primary prevention in patients with both 2TDM and prediabetes/insulin resistance, most likely due to positive effects on atherosclerosis

Diabetes self-management education (DSME) is an essential part of effective and safe treatment of chronic conditions such as diabetes mellitus (DM). Though the data on DSME effectiveness in elderly are limited, all patients should be educated regardless of age. The form of learning and education program may vary depending on the clinical situation and the patient’s characteristics. Age-related problems, so-called geriatric syndromes, determinant heterogeneity of elderly diabetic population. Geriatric syndromes should be taken into account to choose proper treatment goals and optimal education programs. Functional dependency, cognitive decline, depression, sarcopenia, malnutrition and polypharmacy seems to be most important in the education context. The development of geriatric education program with a broad focus on solving both diabetic and age-related problems and its implementation on a wider range of institutions may be useful to improve diabetes self-management education of elderly in clinical practice. It is also necessary to initiate clinical studies to evaluate DSME effectiveness in elderly not only from the generally accepted diabetological criteria, but also considering its impact on age-related problems.

Introduction. Androgenic deficiency is an important pathogenetic element in the development of metabolic syndrome and cardiovascular diseases in men. It has been proven that in male patients with type 2 diabetes, hypogonadism develops much more often. Objective – to study the metabolic and cardiovascular features of the course of type 2 diabetes mellitus (T2DM) in men with androgen deficiency.

Materials and methods. The study included 124 men with type 2 diabetes. To diagnose hypogonadism, the levels of total testosterone (T), sex hormone binding globulin (SHBG), albumin and luteinizing hormone (LH) were measured. Free testosterone (free T) levels were calculated using a calculator from Ghent University Hospital, Belgium. A retrospective analysis of case histories was carried out (spectrum of late complications, the presence of heart attacks and strokes, laboratory data – total cholesterol (CS), triglycerides (TG), fasting blood plasma glucose, basal insulin level, glycated hemoglobin (HbA1c)). The HOMA-IR index was used to determine the degree of insulin resistance.

Results. The average age of men was 57.39 ± 9.41 years. The incidence of laboratory-confirmed hypogonadism is 50.81%. An average positive correlation was found between androgen deficiency and the incidence of non-fatal cardiovascular events (r = 0.45, p < 0.05). There was no statistically significant relationship between the presence of hypogonadism and the incidence and degree of late complications of T2DM. Patients with low T levels tended to have higher HOMA-IR values compared to patients with normal T levels (p < 0.05). At the same time, the indicators of carbohydrate and lipid metabolism did not differ significantly in these groups (p > 0.05).

Conclusions. The revealed incidence of hypogonadism in men with T2DM corresponds to the data of international studies. The presence of a significant correlation between low testosterone levels and cardiovascular events in patients with T2DM suggests that hypogonadism can be used as an additional criterion for cardiovascular risk. Testosterone deficiency exacerbates insulin resistance, which can lead to weight gain and impair carbohydrate metabolism.

The purpose of the presented literature review was an attempt to sum up current estimates of the effect of the use of dipeptidyl peptidase-4 inhibitors (iDPP-4) in the algorithms of both traditional (diabetes mellitus) and a number of alternative nosologies, in particular, oncological and neurological pathology, as well as a new coronavirus infection (COVID-19). To do this, the most large-scale (as a rule) publications of 2018–2021 devoted to the problems under consideration were analyzed. The search was carried out by keywords in the Pubmed information base (ncbi.nlm.nih.gov). Factors contributing to the widespread use of IDP-4 in clinical practice are both pharmacologically clear mechanism of action and efficacy, as well as the possibility of oral use, a successful pharmacokinetic profile, low toxicity, in particular, a low risk of hypoglycemia. Newly obtained data on the mechanisms of mechanisms are discussed. Renoprotective action, the presence of cardioprotection is debated. The biochemical prerequisites for the possible effectiveness of iDPP-4 as blockers of the development of a hyperimmune reaction that causes, in particular, the severe course of the new coronavirus infection are discussed. At the same time, the results of studies of various designs are categorically compared, indicating both in favor of the use of iDPP-4 in patients with COVID-19, and not noticing its expediency. It is concluded that, given the large-scale biochemical role of DPP-4, it is important both to continue the active use of its inhibitors in diabetes mellitus, and to expand attempts to use them in a number of other nosologies, including COVID-19.

Type 2 diabetes mellitus (T2DM) is a polygenic disease that develops as a result of the interaction of hereditary predisposition and environmental factors. The predisposition to develop T2DM is associated with the inheritance of certain alleles of “healthy” genes. More than 100 polymorphic variants of genes that increase the risk of developing T2DM have already been described. Today, genes predisposing to the development of β-cell dysfunction and insulin resistance (IR) are the most well studied. In addition, genes that affect lipid metabolism and eating behavior and genes of some cytokines can participate in the formation of a genetic predisposition to the development of T2DM. Our article reviews the most promising potential areas of application of knowledge about the genetics of T2DM in clinical practice. The first direction is to specify the classification and stratification of T2DM into subclasses/clasters. The second one is an individual assessment of the risk of developing T2DM and its complications. Today, predictive models of the risk of developing type 2 diabetes are not accurate enough for widespread use in clinical practice, but now researchers are actively working to improve their accuracy and effectiveness. And finally, knowledge about the genetics of T2DM can help predict the effectiveness of glucose-lowering therapy. In this review, we also discuss the topic of metabolic disease endophenotypes. The concept of endophenotypes suggests the presence of certain pathogenic common links in the pathogenesis of IR, obesity, T2DM, cardiovascular diseases, non-alcoholic fatty liver disease and chronic kidney disease, which are based on certain polymorphic gene variants. The results of research in the field of genetics of T2DM give us new possibilities for a personalized approach to the management of this complex disease.

The increase in the prevalence of type 2 diabetes mellitus (T2DM) worldwide in young people determines the high relevance in studying the course of this disease. There are difficulties in awareness of this pathology in young people, both in specialists and in patients due to the fact that the long-term outcomes of T2DM in young people are poorly understood. This leads to late diagnosis of diabetes and longer exposure to hyperglycemia leads to high risks of microand macrovascular complications. Clinical symptoms of T2DM with a debut at a young age are different in patients, so this disease is not always diagnosed on time. T2DM in young people (18–45 years) has a more aggressive course, the decrease in the level of β-cells occurs faster than in patients with late-onset T2DM. The risk of developing complications in T2DM with onset at a young age is higher than in late-onset diabetes, mainly due to the longer duration of the disease. With a duration of T2DM in young people of 13.3 ± 1.8 years it was shown that the incidence of nephropathy, neuropathy and retinopathy was 54.8%, 32.4% and 13.7%, respectively. According to the literature, in patients with T2DM at a young age, life expectancy is reduced by 14 and 16 years in males and females, respectively. The course of T2DM is more aggressive in relation to young patients than to middle-aged and elderly patients. T2DM with a debut at a young age is a socially significant disease, due to a decrease in the quality of life, the development of diabetic complications and early disability of the working population.

Introduction. In type 2 diabetes mellitus, an inevitable decrease in the secretion of  β-cells of the pancreas occurs, which requires the  initiation of  insulin therapy. Currently, there have been no studies evaluating the  features of  insulin therapy in patients with diabetes type 2 and morbid obesity.

Objective. To compare the effectiveness of different insulin therapy regimens in patients with type 2 diabetes mellitus and morbid obesity. Materials and methods. 140  patients with diabetes type  2 and morbid obesity were included in  a 24-week prospective, non-blinded, randomized clinical study. The patients were divided into 4  groups: 1  – received basic-bolus insulin therapy in combination with metformin (n = 40); 2 – used prandial insulin in combination with metformin (n = 40); 3 – basal insulin in combination with empagliflozin and metformin (n = 30); 4 – received prandial insulin in combination with empagliflozin and metformin (n = 30). Initially, after 12 and 24 weeks, the level of HbA1c, fasting plasma glucose and during the day, body weight, daily insulin doses, frequency of hypoglycemia, and albumin in daily urine were assessed.

Results. After 24 weeks of treatment, there was no statistically significant difference in the achieved HbA1c level between the groups (p = 0.65); in groups 3 and 4, there was a statistically significant decrease in body weight, daily doses of insulin and frequency of hypoglycemia compared to the first and second treatment groups (p = 0.029, p < 0.001 and p < 0,001, respectively); also registered a decrease in albumin in daily urine by 27% during the study period compared with the first and second treatment groups (p = 0.044).

Conclusions. Administration of iSGLT-2 in combination with both basal and prandial insulin in patients with diabetes type 2 and morbid obesity has advantages over the basic-bolus regimen and the regimen of multiple prandial injections, despite the comparable efficacy.

The increase in the prevalence of diabetes mellitus has accelerated significantly in recent years. The situation has been greatly complicated by the COVID-19 pandemic. On the one hand, diabetes mellitus is a risk factor for a severe course of infection, and on the other hand, COVID-19 increases the risk of developing diabetes mellitus. There remain other negative factors that reduce the effectiveness of measures taken to combat the disease: lack of public awareness about diabetes, its effects and preventive measures, which contributes to low vigilance against the disease and neglect of active prevention of diabetes in order to eliminate correctable risk factors. In turn, this leads to an increase in the number of people with insulin resistance and prediabetes. Another important aspect is the lack of effective continuous glycemic control in many patients with diabetes, which increases the risk of complications and disability later in life. The availability of drugs for treatment, especially insulin, is also a problem that can be solved by developing and introducing biosimilars of original insulin drugs on the pharmaceutical market. An important condition for the possibility of transferring patients to more affordable insulin biosimilars is comparability with the reference insulin at all stages of preclinical and clinical trials, proven in accordance with current ESE recommendations. These include the use of the hyperinsulinemic euglycemic clamp method to evaluate pharmacokinetics and pharmacodynamics, as well as immunogenicity studies.

Insulin resistance (IR) is an important problem of humanity, which leads to development of many metabolic disorders. Сurrently the pathogenic mechanism of the development of IR is not completely investigated. Nevertheless, there are some hypotheses explaining the development of this condition. These include such hypotheses as the hypothesis of thrifty genotype, thrifty phenotype, hormonal, stress, good and bad calories, chronic metabolic inflammation, microbiotic and integrated model suggested by Professor Rainer Straub. In this article, the microbiotic theory will be considered in detail, explaining the mechanism of the development of peripheral tissue insensitivity to insulin in dysbiosis due to amplification of transmission by proinflammatory molecules from the intestine to the bloodstream and activation of systemic inflammation, disruption of the “gut-brain-periphery” mechanism and impaired receptor interactions of active intestinal metabolites of the gut microbiota (GM) at the level of cells of metabolic organs. The value of this theory is that its factors affect all links in the pathogenesis of the development of IR, reflected in the integrated model of Professor Straub. In this review the influence of GM and metabolic processes of human body on the development of IR will be considered in detail, data from clinical studies about the influence of GM (its composition, active metabolites, individual bacterial strains) on the development of IR and the role of chronic metabolic inflammation in this process will also be presented. In addition, attention will be paid to bidirectional effects of GM and metformin, as well as to data from clinical studies on changes in GM in healthy people and people with IR under the influence of metformin and how GM affects the pharmacokinetics of this drug. The possibility of IR correction through the use of dietary fiber will also be considered.

Today, prediabetes is regarded by the world medical community as early diabetes mellitus. The accumulated research evidence shows that prediabetes is characterized by a spectrum of complications that are similar to those of diabetes mellitus, which means that the deterioration of cardiovascular prognosis starts already at the stage of prediabetes. In the current timeframe, metformin is actually the only drug that is widely prescribed for the treatment of prediabetes to prevent type 2 diabetes mellitus and cardiovascular diseases associated with insulin resistance and hyperinsulinemia. Meanwhile, metabolically unhealthy obesity characterized by hyperinsulinemia and insulin resistance is associated with a significantly unfavourable course of prediabetes, as well as the highest risk of developing both type 2 diabetes mellitus and cardiovascular diseases, development/ progression of chronic kidney disease. The theme of this review is the priority of metformin for the management of the most prognostically unfavourable phenotypes of prediabetes. The review is also devoted to the description of the most significant mechanisms that provide effects of metformin underlying the management of key disorders that determine the unfavourable prognosis of prediabetes. In particular, it sets forth the role of unhealthy nutrition, its effects on the development of imbalance of the composition of gut microbiota, which, in turn, entails a cascade of metabolic disorders underlying the development of metabolic ill health. The review sets forth the key role of metformin as a drug that protects against the development of these disorders. The information presented in this review will be useful to personalize the choice of both the scope and nature of interventions in patients with different phenotypic characteristics.

Cardiovascular diseases are a frequent comorbid condition in patients with type 2 diabetes mellitus (t2DM). This problem tends to remain acute because of the progression of t2DM, which increases the chances of cardiovascular events. Medicine today has a range of innovative hypoglycemic drugs, which proved their safety and effectiveness towards diseases of cardiovascular system. However, high cardiovascular mortality demonstrates that the medication is not enough effective. Partly lack of success may be explained by not enough work with unmodified risk factors, such as physical activity, smoking and excessive and wrong nutrition. Studies about dietary fiber (DF) let us discuss their including in the dietary plan of patients with t2DM and cardiovascular diseases. One of the promising DF types is Cyamopsis tetragonoloba extract. It showed its effectiveness concerning carbohydrate metabolism and lipid profile, improving, metabolic features of t2DM patients and lowering the risks of cardiovascular events. What is more, the advantage of Cyamopsis tetragonoloba extract is easy to use and has no side effects.

Synthetic glucocorticoids are widely used in pregnancies at risk of preterm delivery and in pregnant women at risk of having a child with severe 21-hydroxylase deficiency. The positive effects of reducing mortality in preterm and virilisation in girls with congenital adrenal hyperplasia are now unquestionable. The adrenogenital syndrome responding to 21-hydroxylase deficiency is a common, potential fatal disease. Its incidence calculated on the basis of neonatal screening data makes 1 case for 14000 live newborns among the worldwide population, 1 for 9638 – In Russia. DEX passes through the placenta and decreases fetal ACTH production thereby suppressing the fetal production of androgens. The prenatal treatment does not preclude from a life-long treatment in future and it is not prevention of a salt-losing syndrome at the postnatal period, and dexamethasone safety in relation to cognitive development of children prenatally treated with dexamethasone is still up for debate. Adding to the concern is the fact that the doses of DEX that the fetus is exposed to are estimated to be 60 times the normal fetal cortisol level. The glucocorticoid and the mineralocorticoid receptors are highly expressed in the hippocampus, amygdala, and prefrontal cortex. These areas, important for executive functioning, emotional regulation, and memory, are vulnerable to high doses of GCs. Most experimental data from animal have shown that prenatal exposure to synthetic glucocorticoids programs the foetal HPA and may lead to altered susceptibility to metabolic and cardiovascular disease i.e. metabolic syndrome, high blood pressure. Prenatal glucocorticoid exposure also leads to modification of HPAassociated behaviours and cognition.

Introduction. In the cases of neurosurgery failure in acromegaly treatment, drug therapy with somatostatin analogues (SSA) octreotide or lanreotide is indicated. The effectiveness of SSA is limited by the presence of resistance, there is an opinion that in some cases it can be overcome by replacing one drug with another.

Aim. Own experience analysis of transferring acromegaly patients from therapy with long-acting octreotide to lanreotide autogel 120 mg.

Materials and methods. The case histories of acromegaly patients who were recommended to replace long-acting octreotide therapy with lanreotide therapy 120 mg were analyzed. GH and insulin-like growth factor-1 (IGF-1) dynamics was evaluated at least 6 months after the replacement of the drug. The target value for GH was considered to be less than 2.5 micrograms/l, for IGF-1 – an excess of no more than 30% of the upper normal limit.

Results. 24 patients were transferred to lanreotide therapy 120 mg. Of the 19 patients with insufficient reduction of GH and IGF-1 on prolonged-acting octreotide therapy at a dose of 40 mg every 28 days (OCT40) the prescription of lanreotide 120 mg every 28 days (LAN120) led to the target values of both GH and IGF-1 in 4 (21%) cases. These patients had no more than a twofold excess of IGF-1, and the level of GH was less than 2.5 mcg/l on the background of OCT 40 therapy. In 6 (32%) patients, IGF-1 levels normalized or decreased, but GH remained outside the target values. In 9 (47%) cases, the replacement of the SSA did not lead to a significant positive dynamics in the levels of GH and IGF-1. The effects of lanreotide therapy 120 mg in another five patients initially treated with octreotide 20 mg are also described.

Conclusions. Replacement of OCT4 with LAN120 may be effective in some patients with acromegaly. A slight increase in the level of IGF-1 together with the target values of GH before replacing the SSA may be the predictor of success.

Introduction. Today the search and development of new methods for diagnosing organic or functional pathology of the thyroid gland with an asymptomatic or clinically nonspecific course is an urgent task of endocrinology and therapy. The functioning of the thyroid gland and the state of the human intestinal microbiome are dynamically interrelated. One of the considered promising methods is mass spectrometry of microbial markers of the human intestinal microbiota.

The purpose of the study. To study the microbial spectrum and characteristics of the biotic environment of the intestine in patients with thyroid diseases.

Materials and methods. 21 patients were examined (8 men and 13 women, median age 40.5 [31.75; 54] years, respectively; 15 with thyroid disease, 6 without thyroid disease). In addition to the standard clinical and laboratory-instrumental examination, patients, colon contents were examined by chromatography-mass spectrometry of microbial materials. The work used descriptive non-parametric statistics with subsequent interpretation. Mean values of indicators and their variance are presented as median, upper and lower quartiles. In relation to representatives of the fecal microbiota, in addition to absolute values, the frequency of occurrence of the microorganism within the reference range, moderate or pronounced deviations was taken into account. The determination of the statistical significance of differences in the relative frequency value was carried out using Fisher’s exact test. The presentation of the results is implemented in the form of range diagrams, compactly depicting a one-dimensional probability distribution, tables. Results. Differences in the composition of the microbiota of the control group and the experimental group for Alcaligenes spp., Staphylococcus spp., Megamonas hypermegale, Peptostreptococcus anaerobius were revealed.

Conclusions. The development of thyroid gland pathology is accompanied by significant deviations in the composition of the fecal microbiota, determined by mass spectrometry of microbial markers. In persons with thyroid pathology, in the absence of clinically significant external influences on the intestinal microbiome, a pronounced decrease in the level of Alcaligenes spp., Staphylococcus spp., is detected, a tendency to a decrease in the level of Megamonas hypermegale, Peptostreptococcus anaerobius is determined. Further differentiated study of the composition of the intestinal microbiome in patients with thyroid diseases is required, depending on the nosological affiliation and the nature of the endocrine dysfunction.

Currently, the incidence and prevalence of chronic kidney disease (CKD) are increasing annually worldwide, and clinical data show that CKD patients commonly experience relative vitamin D insufficiency or deficiency. Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT is an adaptive and in many cases ultimately maladaptive process that develops in response to declining kidney function, impaired phosphate excretion, failure to bioactivate vitamin D and hypocalcemia. SHPT is characterized by persistently elevated levels of parathyroid hormone (PTH) and complicated by important disturbances in mineral metabolism. Maintaining the level of vitamin D and parathyroid hormone concentrations in the target range reduce its associated complications (e.g., fractures, chronic kidney disease and cardiovascular calcification). Effective therapeutic interventions are highly desirable if the morbidity and mortality associated with uncontrolled SHPT are to be reduced. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. However, because of the difficulties associated with lowering PTH while simultaneously controlling serum levels of calcium and phosphorous, traditional therapies for managing SHPT have several limitations. Selective vitamin D receptor activator paricalcitol mainly targets vitamin D receptors (VDR) in the parathyroid glands, has less effect on VDR in the intestine and other tissues, inhibits PTH strongly, triggers less hypercalcemia, and has less effect on intestinal absorption of calcium, phosphorus and bone metabolism and significantly lowers renin levels, albuminuria and blood pressure, which is supported by the results of most studies conducted over these decades. The article is devoted to the problem of treatment of patients with SHPT inpatient with renal replacement therapy with program hemodialysis.

Introduction. One of the key factors contributing to the development and progression of obesity is impairment eating behavior (EB). Therefore, drug therapy for obesity should not only reduce hunger, contributing to weight loss, but also reducing the severity of EB disorders.

Aim. Assess the representation of different types of EB in obese patients, the effect of sibutramine therapy on dynamics EB by The Dutch Eating Behavior Questionnaire (DEBQ) and for hunger/satiety on a visual analog scale (VAS). Quality life of patients, adherence to treatment of obese patients and their weight dynamics in different types of EB during therapy with sibutramine was also assessed.

Materials and methods. The study included 36 obese patients (30 women and 6 men), mean age 38.7 ± 10.8 years, mean body weight 102.8 ± 16.4 kg, body mass index (BMI) 36.8 ± 4.6 kg/m2, receiving therapy with sibutramine at a dose of 10 mg per day once in the morning before meals in combination with hypocaloric nutrition.

Results and discussion. The study showed the prevalence of the emotiogenic type of eating disorders in patients. However, it was pointed out that sibutramine therapy combined with hypocaloric nutrition proved its efficacy in any type of eating disorders. Positive dynamics anxiety/depression in subclinical conditions during treatment with sibutramine was also revealed.

Conclusion. Sibutramine treatment may be recommended for the development of a new EB model in obese patients because it is effective in reducing weight in any type of EB disorder.

Octreotide is a first-generation somatostatin analog that has been used for 40 years for the medical treatment of acromegaly, both after neurosurgical intervention and as first-line treatment. The frequency of biochemical control against the background of extended-acting octreotide varies from 25 to 56% depending on growth hormone and IGF-1 levels at the disease debut, presence of previous surgery, patient gender and age, treatment compliance and the dose of octreotide used. Longterm clinical experience with prolonged-acting octreotide demonstrates that more than half of patients require an increase in dosage to 30 mg or higher. If during treatment with Octreotide in a dose of 30 mg for 3 months there is no normalization of IGF-1 level, but there was a decrease of 50% or more of the initial level, further dose increase to 40 mg is possible, because this increases the effectiveness of treatment without increasing the frequency of side effects. Foreign researchers have shown that high doses of Octreotide (60 mg every 28 days) can improve biochemical control in patients who have not fully responded to therapy with doses of 30–40 mg of extended-acting Octreotide. Further studies are needed to determine the optimal dose of prolonged octreotide in acromegaly therapy, both at the start of treatment and during treatment. Management of patients by a team of specialists involved in the treatment of pituitary tumors will allow faster achievement of biochemical control of acromegaly.