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Background. In patients with newly diagnosed type 2 diabetes mellitus (T2DM), a small but statistically significant decrease in absolute number of natural killer (NK) cells (CD56+) in the peripheral blood (PB) was found, especially pronounced with concomitant obesity. In connection with the above, one of the main aims of the present report was to further study the role of NK cells in patients with newly diagnosed T2DM, including those with obesity. For this purpose, a combination of flow cytometry methods with scanning and transmission electron microscopy was used to determine the number and function of CD56+ cells in the PB of patients with T2DM. Materials and methods. We examined 144 patients of both sexes with newly diagnosed T2DM aged 40–70 years who had no other acute or chronic diseases and had not previously taken any hypoglycemic drugs. The control group consisted of 50 healthy individuals with normoglycemia aged 40–65 years who had not COVID-19 disease. Results. Our studies have found that in untreated patients with newly diagnosed T2DM compared to healthy controls, there is a very small statistically significant decrease in the absolute number of CD56+ cells in the PB. When combining flow cytometry (FACS method), transmission and scanning electron microscopy in patients with T2DM, a significant change in the ultrastructure of CD56+ cells was revealed, indicating a decrease in their function (an increase in the number of cells with a smoother surface of the cell membrane, a sharp decrease in the number of azurophilic granules in the cytoplasm considered the main producer of cytokines and perforins, the appearance of parallel tubular structures, biomarkers of decreased cell function, a disruption of the Golgi apparatus structure, granular endoplasmic reticulum, etc.). The data obtained indicate that at the initial stage of T2DM development in humans, there is a pronounced weakening in the function of NK cells and, consequently, the natural immune defense of the body and explain the increased susceptibility of diabetics to various viruses and infections, including COVID-19, and also more severe clinical course and increased mortality. Conclusions. The conducted studies show that in patients with T2DM who are at the initial stage of T2DM, there is a sharp disturbance in the submicroscopic organization of CD56+ cells, the most important cellular element of natural immunity, which suggests a weakening of the function of natural immune defense. It is the main cause of increased sensitivity of diabetic patients to infection with various pathogens, including the SARS-CoV-2, as well as more severe clinical course and increased mortality rate.

Background. Vitamin D deficiency (VDD) is widespread in the world; its proportion varies considerably in different populations and depends on many causes. Up to now, there were no National recommendations for the diagnosis, prevention, and treatment of VDD in adults in Ukraine. Their creation became the purpose of this work. Methodology. Consensus was created using the Delphi method, voting was conducted using the SurveyMonkey® platform. After approval of the composition of the Consensus Group, agreement on the order of formation and structure of the Consensus, creation and correction of the main statements, and two voting rounds, the main Consensus statements were formed and were successfully voted on. The 15 authors of the article are 15 experts who participated in the voting. The final 14 Consensus statements are presented in this article. Each statement is preceded by a justification based on high-quality evidence available in the current literature. Results. Despite the reduction of VDD in the Ukrainian population in recent years, experts have recommen­ded increasing the awareness of the medical community and the Ukrainian population about the problem and ways to overcome it, with a screening of the total serum level of 25-hydroxyvitamin D (25(OH)D) in subjects from the groups of risk to achieve the target concentration of 30–50 ng/ml (75–125 nmol/l). To ensure it, we recommend the individual selection of a prophylactic dose of vitamin D (800–2000 IU/d for young healthy persons and 3000–5000 IU/d for patients with diseases and conditions that affect the metabolism of vitamin D). For the treatment of VDD, we recommend short-term intake of higher doses (4000–10,000 IU/d) of vitamin D with control of the 25(OH)D level after 4–12 weeks of treatment and subsequent use of maintenance doses. Also, we re­commend the determination of serum 25(OH)D level before the initiation of antiosteoporotic therapy in patients with osteoporosis and its complications to prevent its ineffectiveness and increase the safety profile.

Research objectives: to evaluate the activity of apoptosis and proliferation mechanisms of eutopic endometrium in patients with adenomyosis who had a history of papillary thyroid carcinoma (PTC). Materials and methods. 63 women of reproductive age were examined: group I – 31 patients with adenomyosis and PTC in history, group II – 32 patients with adenomyosis and normal thyroid status. The intensity of pelvic pain was assessed using a visual analog scale in all women. The material for morphological research was obtained with Pipelle biopsy of the endometrium in the secretory phase of the menstrual cycle. A morphological study was performed on 30 biopsies of eutopic endometrium (15 samples from patients of group I and 15 samples from patients of group II). An immunohistochemical study was performed using monoclonal antibodies to cell-specific markers Bcl-2 (DAKO, clone 124) and Ki-67 (DAKO, clone MIB-1). Results. High expression of Bcl-2 was detected in the endometrial glandular epithelial cells (EGECs) in 70% and 62.5% of samples in group I and II respectively (р > 0.05), the number of Bcl-2-positive cells was significantly higher in samples from group I (80.0 ± 13.1% versus 60.0 ± 15.2% in group І and ІІ respectively, р < 0.05). In endometrial stromal cells (ESCs) high expression of Bcl-2 was detected in 90% and 100% of samples from group I and II respectively (р > 0.05), no significant difference in the number of positive cells was found between groups (18.9 ± 12.2% and 12.6 ± 9.1% in group І and ІІ respectively, р > 0.05). Expression of Ki-67 was detected in the EGECs in 70% and 62.5% (р > 0.05) of samples in group І and ІІ respectively and in the ESCs in 100% of samples from groups I and II respectively. The immunocytochemical Ki-67 labelling index was much more prominent in group I (45.0 ± 11.4% versus 25.8 ± 16.7% EGECs (р < 0.05); 26.5 ± 10.2% versus 16.3 ± 8.9% ESCs (р < 0.05) for group I and II respectively). Conclusions. Altered proliferation of the eutopic endometrium with marked resistance to apoptosis was found in reproductive aged female with adenomyosis and PTC in history, that is can be considered as a marker of the aggressiveness of the disease course in this cohort of patients.

Background. The morphology of the thyroid in Graves’ disease (GD) can be quite diverse: in most cases there is a diffuse enlargement of the thyroid gland (diffuse goiter), in some cases it is not increased, and in some patients there are focal neoplasms (single and multiple), including thyroid cancer. According to some studies, in patients with Graves’ disease, focal formations are observed in 10–31% of cases, and in half of the patients, they appear against the background of treatment with thionamides. The purpose of this paper was a retrospective study of the morphological features of benign thyroid neoplasms due to GD based on the results of cytological and pathomorphological studies. Materials and methods. The study was performed at the clinic of the State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. All patients with GD who were operated in the Department of Endocrine Surgery from 2008 to 2019 (1854 patients) were first selected, and then those who had benign focal formations according to the pathohistological examination were selected among them. Results. The frequency of benign thyroid neoplasms in GD is 22.06 % in women aged 26 to 55 years. Cytological studies of thyroid neoplasm punctures in GD made it possible to clearly establish their benign nature (BSRTC-2) in 94.3 % of cases. In 5.7 % of cases, cytological categories BSRTC-3 and BSRTC-4 were established. Positive immunocytochemical reactions to thyroid peroxidase and thyroglobulin, and the absence of CK17 allow avoiding cytological overdiagnosis, characteristic of benign neoplasms of the thyroid gland in GD. Conclusions. Among pathohistologically confirmed benign neoplasms of the thyroid gland in GD, in 63.82 % of cases a histological diagnosis was adenomatous or colloid goiter, in 34.47 % — signs of nodular hyperplasia, in 1.71 % — the presence of thyroiditis.

Stem cell (SC) differentiation requires a series of chromatin rearrangements to establish cell identity. Posttranslational modifications of histones usually regulate the dynamics of hete­rochromatin. Histones are subjected to various modifications, such as acetylation, methylation, phosphorylation and ubiquinination, and thus contribute to regulation of chromatin status and trans­criptional activity. The chemically stable pattern of methylated histones promotes cellular memory relative to external stimuli, maintaining transcription levels of adaptive genes even after elimi­nation of environmental signals. Chromatin mo­difications play an important role in the maturation of pancreatic islet cells, the establishment of a secretion pattern that stimulates the regu­lation of insulin secretion. MicroRNAs, a class of endo­genous small noncoding RNAs in eukaryotes, are important regulators of gene expression at the level of posttranscriptional mecha­nisms. MicroRNAs regulate insulin secretion, pancreatic deve­lopment, and β-cell differentiation. Pluripotent SCs are characterized by a high rate of proliferation, the ability to self-repair and the potential for differentiation in different cell types. This rapid proliferation is due to a modified cell cycle that allows cells to rapidly transition from DNA synthesis to cell division by reducing the time of gap (G1 and G2) phases. The canonical WNT/β-ca­tenin signaling pathway is characterized as a major driver of cell growth and proliferation. At G1, WNT signaling induces a transition to the S-phase. Compared to their somatic counterparts, pluripotent SCs exhibit a high rate of glycolysis similar to aerobic glycolysis in cancer cells, a phenomenon known as the Warburg effect, which is important for maintaining SC properties. In stem cells, the extracellular influx of Ca2+ into the cytoplasm is mediated mainly by depot-controlled Ca2+ channels. Extracellular cal­cium has been shown to promote SC proliferation and thus may be involved in transplant therapy.

Background. Increased level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 (ApoA1) in plasma is associated with a reduced risk of developing cardiovascular diseases. In addition to its potential cardioprotective function, HDL and ApoA1, the main HDL apolipoprotein, also have antidiabetic properties. The aim of the study was to determine the level of ApoA1 in the blood of patients (n = 81) with diabetes mellitus and COVID-19. Materials and methods. ApoA1 was determined by enzyme-linked immunosorbent assay kits (Elabscience, USA). The measurements were performed at an optical density of 450 nm. Results. ApoA1 level in the blood of patients with diabetes and especially with COVID-19 was significantly lower than in healthy people. The study of the dependence of plasma ApoA1 content on the level of Hb1Ac, the gender and the type of diabetes showed that in blood of patients with type 2 diabetes the amount of ApoA1 is lower than in those with type 1 diabetes, and with an increase in the level of Hb1Ac the amount of ApoA1 decreases. There was also significant gender difference. With an increase in the body mass index, the content of ApoA1 in blood plasma decreases below normal — 0.9 g/L, and at body mass index < 25 kg/m2, the amount of ApoA1 is significantly higher than the average lipoprotein level in diabetic patients. In individuals with newly diagnosed diabetes, the level of ApoA1 is significantly higher, and in patients with more than 10 years of illness, it is below average and below normal. Biguanide treatment, either in combination with other drugs (mainly insulin) or as monothe- rapy, does not significantly affect the level of ApoA1 compared to the entire group average. In patients treated with sulfonylurea, the level of ApoA1 is significantly lower than the average level for the group and the norm. A significant positive effect on the amount of ApoA1 in plasma was observed in people treated with a combination of drugs with sodium-glucose cotransporter type 2 inhibitors, insulin and especially dipeptidyl peptidase-4 inhibitors. However, insulin monotherapy did not significantly affect the ApoA1 content. Possible mechanisms of ApoA1 decrease in COVID-19 and diabetes are discussed. Conclusions. Thus, the level of ApoA1 may be one of the promising markers of severe COVID-19.

Background. Vitamin D (VD) is a versatile steroid hormone that regulates the activity of several thousand genes. Over the past decades, numerous diseases associated with VD deficiency have been reported, including cancer and autoimmune thyroid disorders. Researches revealed that VD can influence the development and course of these diseases. The VD participation in modulation of the hypothalamus-pituitary-thyroid gland axis, both at the level of the pituitary gland and at that of the thyroid, has been shown. The effect of VD on autoimmune diseases, including thyroid autoimmune diseases, is widely studied. Most of the existing data support the relationship between VD deficiency and a greater tendency to develop and higher antibody titers associated with Hashimoto’s thyroiditis, Graves’ disease (GD) and postpartum thyroiditis. An important fact is that epidemiological studies have demonstrated a high prevalence of VD deficiency or insufficiency throughout the world. VD insufficiency is a potent dietary trigger that results in severe, chronic diseases. The question arises how reliable is the relationship between VD and autoimmune thyroid diseases (AITD). Although the results of the studies performed are somewhat contradictory, the vast majority of data indicates a link between VD deficiency and an increased risk of developing the disease, high antibody titers, and difficulties in treatment. Genetic polymorphisms associated with VD function and metabolism also have some influence on the risk of ATD. With regard to the precise nature of the relationship between VD and AITD, it is believed that VD plays a small but significant role in the AITD pathogenesis. After the AITD development, its consequence may be an increase in VD deficiency. It is the need to determine the effect of VD supplementation in the prevention and treatment of AITD and its optimal level directly for clinical practice. It is necessary for clinical practice to determine the effect of VD supplements in the prevention and treatment of AITD and its optimal level. A study, the purpose of which was to study the content of VD, namely 25(OH)D in 176 patients with GD complicated by autoimmune ophthalmopathy (AO) and to identify a correlation relationship with antithyroid antibodies (TPO, TSHR-Ab) was carried out at the State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. Materials and methods. The levels of 25(OH)D, TSH, TSHR-Ab, TPO were determined by enzyme immunoassay using standard kits from Siemens firm. During the study, 176 patients were divided into two groups, depending on the presence of AO: the first group consisted of patients with GD without AO (62 people), the second group included patients with GD and AO (114 people). Results. In GD, 91.78 % of patients (161 people) have an insufficient level of 25(OH)D content: a suboptimal level was recorded in 42 patients (23.86 %), and a deficit — in 119 patients (67.61 %). A significant negative correlation relationship was revealed between TSHR-Ab and 25(OH)D in the group of patients with GD and AO — with a lower level of 25(OH)D, the higher values of TSHR-Ab correlate. Compensation of the 25(OH)D deficiency leads to a significant (P < 0.05) decrease in the levels of TSHR-Ab and TPO in patients with GD. Besides, there is a large body of literature available lin-king vitamin D to thyroid autoimmunity as a result of cross-sectional studies and observations. Conclusions. Thus, there is still an urgent need for large multicenter studies to evaluate the effect of vitamin D supplementation on meaningful long-term clinical endpoints in AITD.

The aim of the study was to investigate the effect of obesity on the development of cancer of certain localizations in patients with type 2 diabetes mellitus (T2D) and to explain the association mechanisms of obesity in diabetes and cancer. The study included retrospective analysis of first time diagnosed cancer cases in patients with T2D in 2012-2016 in Ivano-Frankivsk region. Analysis of the data was carried out using Statistica 12.0 (StatSoft Inc., USA) program. The data are presented in the tables as M ± SD (M ± standard deviation). Differences between the studied parameters were determined using the ANOVA- test, taking into account the Bonferroni correction. The relationship between the studied data was evaluated using the criterion of chi-square with Yates correction (χ²). The odds ratio (OR), 95% confidence interval, the positive and negative predictive value were calculated to determine the association between two events. The differences were considered significant at p < 0.05. According to the results, 533 cases of the first time diagnosed cancer were detected in patients with T2D. It was found that obesity is inherent in women with breast, uterine, ovarian and colorectal cancer; for men with prostate cancer and with colorectal cancer. According to the criterion of χ², the effect of obesity on the incidence of breast cancer in women (x2=8.46; p

Background. Determination of the blood lymphocyte immunophenotype is one of the key indicators of the immune function in a diseased person. However, the studies of the lymphocyte immunophenotyping in patients with type 2 diabetes (T2D), with the most frequent complication of this disease — overweight/obesity, are rare and controversial. The purpose of study was to determine immunophenotype of blood lymphocytes (CD3+ T, CD4+ T, CD8+ T, CD20+ and CD56+ cells) in patients with newly diagnosed T2D and different body mass index (BMI). Materials and methods. There were examined 78 patients with newly diagnosed T2D and 40 normoglycemic individuals, who were divided into 4 subgroups, depending on the BMI. The blood lymphocyte immunophenotyping was carried out by the flow cytometry using a FACStar Plus laser cytofluorimeter and a panel of monoclonal antibodies to membrane antigens of lymphocytes. Results. The entire group of patients with T2D is characterized by a small but significant (p 35.0 kg/m2, it was found that in subgroup 1, the absolute number of CD3+ T, CD4+ T, CD8+ T, CD20+ and CD56+ cells was close to those in normoglycemic individuals. Patients of subgroup 2 showed a significant increase in the absolute number of CD4+ T cells by 12.5 % (p

Diabetic patients are in the spotlight from the early stages of a pandemic, as growing epidemiological data show they are at higher risk for severe clinical outcomes from COVID-19. As the global COVID-19 pandemic continues to evolve, it is also becoming increasingly apparent that the interactions between COVID-19 and diabetes mellitus (DM) are complex pathophysiological mechanisms. The outcome of COVID-19 is more severe in people with DM, which has the potential to accelerate the onset of acute metabolic complications of DM such as diabetic ketoacidosis and hyperglycemia. These mechanisms underlying these associations remain unclear, but they likely include the angiotensin converting enzyme receptor 2, a binding site for SARS-CoV-2, which is expressed in key metabolic organs such as in the pancreas, in particular in β-cells. The potential β-cell tropism of SARS-CoV-2 can damage cells and impair insulin secretion, causing hyperglycemia and ketoacidosis. Understanding the bidirectional interaction between DM and COVID-19 will be critical to protecting and treating people with DM. Current epidemiological data on COVID-19 do not support the hypothesis that diabetic patients are at increased risk of infection compared to the general population. To date, it has been established that decompensated DM is an independent factor that aggravates the course of coronavirus infection and significantly increases the risk of a fatal outcome of the disease. The review provides a brief summary of the evolution of pathogenetic and clinical aspects for understanding the mechanisms of this pathological tandem, as well as therapeutic strategies for treating patients with COVID-19 and DM. As the incidence of DM continues to rise globally, more than ever, diabetes prevention and control must be a priority for health systems around the world.

Background. Type 2 diabetes mellitus (T2DM) is closely associated with an increased risk of cardiovascular diseases. It was shown that endothelial dysfunction is one of the key pathological events in the development of chronic vascular diabetic complications. An important effect of endothelial dysfunction is that it increases the production and biological activity of the potent vasoconstrictor and the pro-inflammatory peptide — endothelin (ET). Metformin is used in the treatment of T2DM as a first-line medication. It has been shown that the mechanism of action of metformin may be associated with biochemical processes in the gastrointestinal tract. Brain natriuretic peptide (BNP) is used as a marker in the diagnosis of heart failure. The purpose of this work was to determine and compare ET-1, NT-proBNP and glucagon-like peptide-1 (GLP-1) blood levels in diabetic patients treated with metformin. Materials and methods. NT-proBNP, GLP-1, endothelin-1 and glycated hemoglobin were determined using enzyme-linked immunosorbent assay. To compare the data groups, Student’s t-test and one-way ANOVA were used. Results. The content of ET-1 in the blood of patients with T2DM significantly exceeds its concentration in the control samples. Monotherapy with metformin leads to a decrease in ET-1 levels by more than 65 %. The combination therapy of metformin with insulin causes even greater decrease in ET-1. The blood level of GLP-1 in patients with T2DM is significantly, more than 2 times, reduced compared to healthy people. After metformin treatment, the content of GLP-1 is increased to the control level. The concentration of NT-proBNP in the blood of diabetic patients more than 2 times exceeds the control values. Treatment with metformin leads to a decrease in the content of natriuretic peptide by more than 40 %. Conclusions. Thus, treatment with metformin causes a decrease in ET-1 and NT-proBNP concentrations, and an increase in blood GLP-1 of patients with type 2 diabetes. These events together may indicate a positive protective effect of metformin on the cardiovascular system.

Background. According to the current hypothesis, type 2 diabetes mellitus (T2DM) is chronic low-gradient inflammation. Almost 80 % of patients with type 2 diabetes are obese. However, such important biomarkers of inflammation as the leukocyte composition of the blood and the neutrophil-to-lymphocyte ratio (NLR) in patients with newly diagnosed type T2DM and varying degrees of obesity remain poorly understood. The purpose was to study the leukocyte composition and the index of inflammation NLR in non-hematological patients with newly diagnosed type 2 diabetes, depending on different body weights. Materials and methods. The study involved 108 patients with newly diagnosed T2DM aged 40–70 years and 50 normoglycemic individuals with different body mass index (BMI). The total number of blood leukocytes was determined using a hematological analyzer, and the leukocyte composition was determined both with an analyzer and in blood smears stained according to the Pappenheim staining method using a cacodylate buffer (Ph 6.85) per 200 identified cells. The index of inflammation NLR was calculated by dividing the absolute neutrophil count by the lymphocyte count. Results. Compared to healthy people, T2DM patients are characterized by a small but significant (p < 0.05) increase in the total number of leukocytes, the absolute number of neutrophils and monocytes, and the index of inflammation NLR. When dividing the entire group of T2DM patients and healthy individuals into four subgroups, depending on the body weight, it was found that leukocytosis, neutrophilia, monocytosis, and the NLR index in patients with T2DM correlated with the BMI value. At BMI ≤ 25.5 kg/m2, the number of leukocytes in T2DM patients compared with those in healthy individuals was increased by 11.5 %, neutrophils by 20.7 % (p = 0.007), monocytes by 11.1 %, and the NLR index by 19.4 %. With a BMI of 25.9–29.9 kg/m2, the number of leukocytes was increased by 19.2 %, neutrophils by 27.6 %, monocytes by 38.8 %, and the NLR index by 29.7 %. With a BMI of 30.0–34.9 kg/m2, the number of leukocytes was significantly increased by 48.1 %, neutrophils by 58.6 %, monocytes by 105 %, and the index NLR by 32.6 %; and with BMI > 35 kg/m2, leukocytes were increased by 67.3 %, neutrophils by 93 %, monocytes by 97 %, and the index of inflammation NLR by 54.9 %. In healthy individuals, similar changes were observed depending on the leukocyte composition and BMI but less pronounced. Conclusions. The level of leukocytosis, neutrophilia, monocytosis, and the index of inflammation NLR in T2DM patients also largely depends on their body weight, especially obesity. In obesity, the inflammatory process is intensified by summing factors specific to the pathogenesis of T2DM and overweight, this must be taken into account when choosing therapy in patients with type 2 diabetes mellitus, complicated by obesity.

Testosterone is a hormone that plays a key role in carbohydrate, fat and protein metabolism in men. Age-related decrease in testosterone levels, which is facilitated by the development and progression of comorbidities, especially type 2 diabetes mellitus, obesity, dyslipidemia, can have a significant impact on the development of cardiovascular diseases in men and increase the risk of premature death. The paper presents an analysis of modern literature data on the prevalence of late-onset hypogonadism and its impact on the development of cardiovascular pathology in men. An analysis of researches presented in the search database and MedLine database was performed using the keywords “testosterone”, “male”, “late-onset hypogonadism”, and “cardiovascular diseases”. The controversy of a number of hypotheses about the role of androgen deficiency in the development of cardiovascular pathology in men is shown. However, it was determined that most studies showed the correlation between androgen deficiency and the development of metabolic disorders, which are factors for the development of metabolic syndrome, obesity, type 2 diabetes mellitus. In turn, these comorbidities are direct factors that lead to the early onset and progression of vascular pathology and associated mortality in older men. Testosterone therapy is necessary in men with type 2 diabetes mellitus and clinically and laboratory confirmed testosterone deficiency, provided that its safety standards are met. Due to ambiguous results regarding the effect of testosterone on the development of cardiovascular disease, this issue needs further study.

Background. Postmenopausal osteoporosis is an issue of great concern as it results in an elevated risk of fractures with a further negative impact on the elderly women’s health. The osteoporosis may be diagnosed based on the low-energy fractures occurring with no major trauma, or based on the low bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). The purpose of study is to examine 25(ОН)D level, 10-year pro­bability of major osteoporotic fractures, bone mineral density and quality, fat and lean mass and to analyze their associations in the pre- and postmenopausal women. Materials and methods. Three hundred and two women aged 45–80 years (mean age — 61.3 ± 7.7 years) were examined and divided into 6 groups according to the pre- and postmenopausal period duration: group I — premenopau­sal women (n = 36; mean age — 50.1 ± 3.4 years); groups II–VI — postmenopausal women (n = 266; mean age — 62.8 ± 6.8 years). All the examined patients were subjected to bone mineral density measurement by the DXA on Prodigy system (GE Medical Systems, model 8743, 2005) according to the standard protocol. BMD and T-score of the lumbar spine, femoral neck and total skeleton were evaluated. Trabecular bone score of lumbar spine was measured by TBS iNsight (Med-Imaps, Pessac, France). Total 25(ОН)D was assessed by electrochemoluminescent method using Еlecsys 2010 ana­lyzer (Roche Diagnostics, Germany) and Cobas test systems. The 10-year probability of major osteoporotic fractures and hip fractures was calculated by the Ukrainian FRAX model without DXA results considered. Total body fat and lean mass was assayed by the dual-energy X-ray absorptiometry (Prodigy, GE). Results. We found a significant association between the pre- and postmenopau­sal period duration and bone density and quality variables (trabecular bone score (F = 6.85; p

The review deals with the development and achievements in a new scientific direction in medicine studying the pathogenesis of various human diseases — clinical pathophy­siology over the last decades. The latest low-traumatic intravital highly sensitive research methods used in pathophysiology for studying the important vital physiological and immunological processes in an organism of patients with type 1 and type 2 diabetes mellitus made it possible to show that the etiopathogenesis of these diseases in humans significantly differs from that in animals with experimental diabetes mellitus. This made it possible to obtain more accurate information about the causes and natural course of diabetes mellitus in humans that requires the development of new methods for its diagnosis, especially at the preclinical stage of development and to stimulate the development of more effective agents for the prevention and treatment of this disease.

Background. Diabetic neuropathy is the most common complication of diabetes mellitus (DM), found in 30–90 % of patients. The relevance of the study is due to the prevalence of diabetic neuropathy, as well as assessing the effectiveness of the use of methylated form of vitamin B12 in the treatment of patients with DM. The aim of this study was to determine the effectiveness of methylcobalamin (Diacobal, Kusum Pharm) in the complex treatment of patients with DM complicated by diabetic peripheral neuropathy (DPN). Materials and methods. The study was conducted by a simple open method. The Michigan Neuropathy Screening Instrument (MNSI), the Neurological Symptoms Score (NSS), the European Quality of Life Questionnaire (EQ-5D) were used to screen and determine the severity of symptoms of DPN. The neurological examination of patients included an assessment of various types of sensitivity (pain, tactile, vibrational, cold, heat, proprioceptive, pressure sensation). Blood levels of vitamin B12 (cyanocobalamin) were determined in all patients. Diacobal was added to the regimen of traditional treatment for DPN regardless of the levels of vitamin B12. Results. It was shown that DPN is a common complication of DM: according to subjective characteristics (MNSI and NSS scales), its symptoms were detected in 84.3 % of cases among DM patients. Subjective scales, such as EQ-5D, MNSI, NSS, are not enough to assess the presence and degree of polyneuropathy in DM patients. The data of these scales do not correlate with the results of a physical examination, but can be used as an auxiliary method for the analysis of subjective symptoms of a patient. A neurological examination is recommended for DM patients, regardless of whether they present active complaints. DPN was detected in 64.8 % of cases among diabetic patients according to objective criteria for the diagnosis and determination of various types of sensitivity (pain, tactile, vibrational, cold, thermal, proprioceptive, pressure sensation). Determining the level of cyanocobalamin should be used in conjunction with the determination of homocysteine and folic acid. Conclusions. The use of methylcobalamin (Diacobal in a daily dose of 1,500 μg for 3 months) in the complex treatment of diabetic neuropathy in diabetic patients is effective and safe, helps to eliminate the manifestations of diabetic neuropathy and improve the quality of life of patients.

Determining of the proliferative potential of tumor cells is an important task for the diagnosis of thyroid cancer. Therefore, a search for markers characterizing the state of proliferative processes is necessary. Proliferating cell nuclear antigen (PCNA), a protein necessary for the organization of components involved in DNA replication and repair, along with Ki-67 is one of the main markers of proliferative processes. Recent studies have shown its ability to interact with many factors that are involved in several metabolic pathways, including DNA repair, translesion DNA synthesis, DNA methylation, chromatin remodeling and cell cycle regulation. The review presents the data on its structure, function, regulation and involvement in malignant transformation of cells. To determine biomar­kers useful for thyroid cancer diagnosis and installing a panel of markers for the early detection of metastatic carcinomas of the thyroid gland, a number of studies have been conducted, which showed that PCNA levels are almost 2-fold higher in metasta­tic than in non-metastatic tumors. An increased expression of PCNA in thyroid carcinomas was also noted as compared with adenomas. The highest level of PCNA expression was observed in the most aggressive types of thyroid cancer — anaplastic and medullary carcinomas. In differentiated tumors, the amount of antigen was somewhat lower, but it increased markedly in invasive variants of these tumors. PCNA expression was enhanced in B-RAF V600E-positive papillary carcinomas compared with B-RAF V600E-negative. A patient survival analysis that was associated with PCNA and Ki-67 marker levels showed a better prognosis in patients with low PCNA levels. The worse results were observed in patients with moderate PCNA, and the worst prognosis was for patients with high antigen values. The possibilities of suppressing PCNA with specific inhibitors for the treatment of certain types of cancer are discussed.

The results of numerous studies have demonstrated the high effectiveness of bariatric surgery in patients with obesity and type 2 diabetes mellitus (DM). Currently, surgery is one of the most effective ways to decrease body mass, to maintain long-term weight loss and to manage type 2 DM. Particular interest has been generated by the strong positive influence of bariatric surgical interventions on the disruption of carbohydrate metabolism in patients who undergo surgery. This change leads to an improvement in the course of type 2 DM as well as its full remission. This review presents information on the mechanisms associated with glycaemic control improvement in obese patients following the bariatric surgery. This review also contains a comparative analysis of effect of various surgical interventions on DM course, the reasons for postbariatric glycaemia and predictors of the effectiveness of bariatric surgeries in terms of metabolic control in obese patients with type 2 DM. In addition, some information concerning surgical and metabolic complications of bariatric surgical intervention is provided, which needs balanced approach to the treatment method choice.

Background. Joint damage in patients with diabetes mellitus is a common complication and is associated with degenerative dystrophic changes in the periarticular structures. The purpose of our work was to study insulin and leptin hormone levels in patients with diabetic osteoarthritis and to investigate their possible influence on the development of this complication. Materials and methods. Seventy­seven patients were examined, they were divided into groups by the type of diabetes mellitus, the presence and severity of diabetic arthropathy. The content of insulin and leptin in the blood serum was determined by enzyme­linked immunosorbent assay. Results. Diabetic arthropathy was diagnosed in more than 70 % of patients. In persons with diabetic arthropathy, insulin levels were significantly elevated (for type 1 diabetes mellitus — by 38.5 %, for type 2 diabetes mellitus — by 55.6 %), as well as leptin content (for type 1 diabetes mellitus — by 43.8 %, for type 2 diabetes mellitus — by 53.7 %). There is a direct correlation between the severity of joint damage and the levels of insulin and leptin. The severity of arthropathy in patients with type 2 diabetes mellitus directly correlates with insulin resistance. Conclusions. Risk of developing arthropathy in type 1 diabetes mellitus with elevated insulin levels is increased by 3.8 times, with elevated leptin content — by 1.3 times, in patients with type 2 diabetes mellitus — by 2.6 and 1.2 times, respectively. For this sample, it was found that the development of arthropathy does not depend on the type of diabetes mellitus. In women with type 2 diabetes, the risk of developing arthropathy is 6.4­time higher than in men. Thus, an increased insulin and leptin levels can be markers of the presence and progression of arthropathy in patients with diabetes mellitus.

Background. Testosterone deficiency is a medical condition that adversely affects male sexuality, reproduction, general health and quality of life. Testosterone therapy can improve the symptoms of testosterone deficiency and possibly stop the development of comorbid diseases. The purpose of the study is to determine the safety and side effects of substitution testosterone therapy in men with type 2 diabetes mellitus and testosterone deficiency. Materials and methods. Testosterone replacement therapy was carried out in 89 men aged 36–72 years with type 2 diabetes mellitus (duration from 1 to 18 years) and androgen deficiency: first group (35 patients) received testosterone undecanoate (1000 mg), second group (54 indivi­duals) — 1 ml of an oil solution (250 mg) of a mixture of testoste­rone esters. Results. In the examined patients of the first group, the average values of erythrocytes, hemoglobin and hematocrit after the end of the observation period did not change significantly. Mean prostate­specific antigen level 9 months after the initiation of testosterone therapy increased by less than 10 % of the baseline, from 1.48 ± 0.26 ng/ml to 1.62 ± 0.20 ng/ml (p > 0.05). An increase in the volume of the prostate gland was non­significant: 32.1 ± 1.9 cm3 before the start of treatment vs 35.7 ± 1.9 cm3 in 9 months. In men of the second group, the average rates of erythrocytes, hemoglobin and hematocrit after the completion of testosterone replacement therapy did not change significantly. The mean prostate­specific antigen values 9 months after the initiation of testosterone therapy in patients of the second group remained virtually unchanged: 1.22 ± 0.30 ng/ml prior to therapy and 1.24 ± 0.20 ng/ml 9 months after (p > 0.1). An increase in the prostate volume in the examined patients was non­significant: 28.4 ± 2.2 cm3 before the start of treatment vs 31.6 ± 1.6 cm3 in 9 months. Conclusions. The results showed that the use of testosterone with different duration of action in men with diabetes mellitus is an effective and safe method.

The article describes the current understanding of the pathogenesis of different types of thyroid nodules. An algorithm for the diagnosis of thyroid diseases, which is aimed at verifying the morphological structure of goiter before the start of treatment, is presented in order to make the right decision on the indications for surgical treatment and its scope. The main methods for both conservative and surgical treatment of thyroid nodules are considered. The features of the treatment of pregnant women with thyroid nodules have been determined.

The review of the literature summarizes and analyzes the material on inflammatory processes accompanying cardiovascular complications in diabetes mellitus. The role of endothelial dysfunction is shown leading to an increase in the permeability of the endothelium, accumulation of lipoproteins in the vessel wall, their modification, formation and secretion of cell adhesion molecules, which in turn leads to involvement of monocytes and their differentiation into inflammatory macrophages. The role of scavenger receptors in the deposition of cholesterol and the formation of foam cells was noted. The mechanisms of the inflammatory process initiation and the formation of inflammasоmes are considered in detail. The scheme of transduction of proinflammatory signals in the cell and participation of the key factor NF-κB integrating all incoming information and controlling the transactivation of genes involved in inflammation are described. It is shown that inflammation is key process in the development of vascular diseases in diabetes mellitus, and the suppression of these processes inhibits the progression of the disease reducing arterial damage and contributing to their healing.

The second part of the review shows the current approaches to the methods of diagnosis and treatment of various forms of hypogonadism in men.

The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

The historical data on the development of medicine as a science, with an emphasis on aspects of the endocrinology, are given in this paper. The role of Ukrainian and foreign scientists and their contribution to the development of the chemistry of hormones has been clarified in a historical context. The role of schools, academies in shaping the outlook of future scientists and the promotion of best practices is shown. The article shows how the knowledge of medicine was gradually accumulated: clinical manifestations, definition of laboratory differences. The ability to provide pathogenetic treatment to the patient with endocrine disease was possible in most cases only after the industrial synthesis of hormones. The works of many scientists were awarded the Nobel Prize in medicine and physiology. The definition of “hormone”, classification, place of biosynthesis, particularly of the secretion, the industrial synthesis of some of them and the scope of use are presented. Special attention is paid to the description of new methods of synthesis of thyroxine, flutapharm and other substances.

Objective of the research — to evaluate the efficacy of combined hypouricemic therapy in patients with hyperuricemia, urate nephropathy on the background of concomitant pathology (type 2 diabetes mellitus, hypertension) based on the dynamics of uricemia, uricosuria, the functional state of the kidneys, minimizing and eliminating the risk factors for the progression of chronic kidney disease. Sixty seven patients were involved in the study. Correction of hyperuricemia in patients with urate nephropathy and concomitant pathology (type 2 diabetes mellitus, hypertension) using phytodiuretic agent Urolesan® in combination treatment leads to normalization of metabolic processes, improvement of glomerular filtration rate, and a decrease in the level of albumin excretion.

ORIGIN — the longest and most extensive study on Lantus® use in patients with cardiovascular risk with diabetes mellitus (DM) type 2 in the early stages, as well as prediabetes, in which insulin therapy is not indicated now. ORIGIN trial was initiated to investigate the efficacy of therapy with insulin glargine compared with standard therapy in terms of effects on cardiovascular events. The main findings of ORIGIN trial for over 6-year period: — Achievement of target glycemic level doesn’t reduce cardiovascular risks. — Lantus® does not cause the risk of cancer. — Early administration of Lantus® once daily leads to a stable target glycemic control. — In most of patients (58 %) treated with Lantus® the cases of symptomatic hypoglycemia didn’t occur; incidence of severe hypoglycemia was very low (0.01 episodes per 1 patient-year and 0.003 for standard therapy), the incidence of general hypoglycemia was 0.1 episode per 1 patient-year in the insulin glargine group and 0.027 for standard therapy. — Lantus® prevents the progression of prediabetes to diabetes mellitus type 2 (DM occurred in 25 % of those with prediabetes who received insulin glargine, vs. 31 % in the standard therapy, i.e., the risk for DM development was 28 % lower).

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