Carbohydrate Metabolism Disorders Research Articles

The interplay of metabolically associated fatty liver disease and carbohydrate metabolism disorders: Current understanding of pathogenesis and treatment

Metabolic-associated fatty liver disease (MAFLD) is a chronic, non-infectious condition associated with metabolic disorders, including type 2 diabetes mellitus. This review describes current understanding of the MAFLD pathogenesis and its relationship to impaired carbohydrate metabolism, particularly the role of insulin resistance, dysregulated autophagy, and other factors contributing to disease development. Furthermore, it analyzes existing therapeutic approaches to MAFLD management, including the use of ursodeoxycholic acid as an autophagy modulator, as well as various glucose-lowering medications, such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and thiazolidinediones. Additionally, the pathogenetic role of fibroblast growth factor-21 in MAFLD development and the potential clinical application of FGF-21-based therapies are described. Thus, this overview reflects current knowledge regarding the pathogenesis and treatment of MAFLD, highlighting the necessity of a comprehensive approach to managing this condition in the context of its strong association with impaired carbohydrate metabolism

Вторичные мессенджеры инсулина при синдроме поликистозных яичников и методы его патогенетической коррекции

The study of new mechanisms of insulin resistance (IR) formation is a prerequisite for the development of new pathogenetically-oriented therapies of polycystic ovary syndrome (PCOS) and the treatment of associated disorders of carbohydrate and fat metabolism. Important regulators of insulin signaling are its secondary messengers, namely myo-inositol (MI), D-chiro inositol (DCI), and α-lipoic acid (ALA), which mediate various effects of insulin. Consequently, MI induces cellular glucose uptake and enhances glycolysis, whereas DCI stimulates glycogenesis and regulates energy metabolism. The physiologic MI/DCI ratio for oocytes is crucial for oogenesis, steroidogenesis, and the regulation of the menstrual cycle. ALA provides insulinomimetic effects through the induction of glucose translocation into cells, antioxidant and anti-inflammatory effects on pancreatic cells, and the suppression of lipolysis and the reduction of triglyceride levels. A wealth of evidence from large-scale studies, meta-analyses, and systematic reviews has demonstrated the crucial role of MI, DCI, and ALA in the treatment of PCOS. A multitude of studies, including those conducted by the authors, have demonstrated that the administration of these substances results in a reduction in HOMA, levels of glucose, insulin, triglycerides, low-density lipoproteins, and body mass index. This, in turn, has been shown to restore ovulation and the menstrual cycle in women with PCOS, as well as to reduce the risk of cardiometabolic diseases, including diabetes and nonalcoholic fatty liver disease KEYWORDS: polycystic ovary syndrome, inositol, myo-inositol, D-chiro inositol, alpha-lipoic acid, insulin resistance, fat metabolism, nonalcoholic fatty liver disease FOR CITATION: Ivanov I.A., Tabeeva G.I., Smetnik A.A. Secondary messengers of insulin in polycystic ovary syndrome and its pathogenically- oriented treatment. Russian Journal of Woman and Child Health. 2024;7(2):135–143 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-8.

Nutritional support in rehabilitation of victims with severe combined trauma

To evaluate the clinical and rehabilitation effectiveness of the protein module (Fresubin Protein) in therapeutic nutrition in patients with severe combined injury (polytrauma) at the rehabilitation stage in a specialized department (neurosurgery). We examined 43 victims who received a combined injury that required treatment in the intensive care unit with subsequent transfer to a specialized department (neurosurgery). At the stage of treatment and rehabilitation in the specialized department, we assessed the biochemical parameters of carbohydrate, fat and protein metabolism, body composition, as well as energy metabolism using indirect calorimetry, and the functional state of the gastrointestinal tract. In the comparison group, patients received a standard diet at the rate of 30 kcal/kg BW. The main group received a standard diet (30 kcal/kg BW) with the addition of a protein module (0.8 g/kg BW) to the diet as an additional source of protein. In both observation groups, moderate to severe protein-energy malnutrition was diagnosed before the study (decreased total protein level - 50.63±1.3 g/l, albumin - 27.97±0.95 g/l, transferrin - 1.33±0.9 g/l). Anthropometric parameters (BMI=17.1±1.2 kg/m2, BMD=20.15±1.5 cm, OP=22.2±1.1 cm, TKFST=8.4±0.5 cm) indicated a deficiency of the somatic protein pool, lean and fat body mass. No pronounced disorders of carbohydrate and fat metabolism were noted. A correlation was found between the dynamics of protein metabolism and the inflammatory process parameters (CRP, white blood cell count, r=-0.79, p=0.001). Against the background of nutritional support with the inclusion of a protein module in the diet, by the 21st day, patients of the main group showed a reliable (p<0.05) normalization of protein metabolism parameters, an increase in lean body mass. The results of the studies indicate that in victims with severe combined trauma, upon admission to the treatment and rehabilitation stage in a specialized department, despite the intensive care provided in the intensive care unit, moderate to severe protein-energy malnutrition with severe protein metabolism disorders is diagnosed. This is manifested by a decrease in the concentration of total protein, albumin, transferrin, and somatic protein pool. Low lean mass values indicate a deficiency of the protein component of nutritional support, a decrease in lean and muscle mass. The consequence of which is a limitation of the volume of rehabilitation, an increased risk of complications. The identified protein deficiency dictates the need to increase the protein component of therapeutic nutrition. Inclusion of a protein module in the therapeutic nutrition program at the rate of 0.8 g/kg of body weight ensures adequate correction of protein metabolism disorders, overall nutritional status in severe combined injury and creates the prerequisites for increasing the effectiveness of rehabilitation measures.

THE ROLE OF INTRAUTERINE ANTIGEN EXPOSURE IN THE MORPHOGENESIS OF CEREBRAL BLOOD VESSELS

Introduction. The state of cerebral vessels in children of the first year of life with congenital toxoplasmosis, both active and without signs of activity (as models of antenatal antigenic exposure), was considered. The patients were born to mothers whose pregnancy proceeded with mild preeclampsia and perinatal damage to the nervous system. The features of the morphogenesis of the brain vessels of rats after exposure to antigens in the antenatal period were experimentally investigated. Materials and Methods. 119 children of the first year of life were examined. 43 patients with toxoplasmosis, 25 children from women whose pregnancy was complicated by mild preeclampsia, and 28 children with perinatal lesions of the nervous system of hypoxic-ischemic genesis due to antenatal hypoxia of the fetus. The comparison group consisted of 23 healthy children with an uncomplicated antenatal history. Experimental study of the morphogenesis of brain vessels of Wistar rats after intrauterine administration of antigens according to the method of M.A. Voloshin. Results. At 1–2 and 7–8 months of life, in children with antigenic antenatal exposure and perinatal lesions of the nervous system of hypoxic-ischemic genesis, blood flow disorders in the anterior cerebral arteries, vessels of the nail bed, manifestations of endothelial dysfunction and impaired function of the sympathoadrenal system were detected. In the experiment, after the intrauterine introduction of antigens of various nature, an increase in the proportion of the connective tissue component in blood vessels was established, and a significant decrease in the ratio of muscle and connective tissue components from the 1st to the 60th day of postnatal development. Changes in indicators of carbohydrate metabolism and a decrease in glycogen in the anterior cerebral artery of rats 1–60 days of life with antigenic antenatal exposure indicate long-term changes in metabolic disorders of carbohydrate metabolism in the anterior cerebral arteries. By extrapolating the results obtained in the experiment on rats, it is possible to predict metabolic disorders in the vessels of people of the appropriate age, which to a certain extent explains the ultrasound and biomicroscopic changes in vessels, endothelial dysfunction detected in children with antigenic antenatal stimulation at 1–2 and 7–8 months of life. Conclusions. The identified features indicate a change in the morphogenesis of brain vessels after antenatal antigenic exposure and are the background for the formation of central nervous system pathology in children

Молекулярно-генетические предикторы перинатальных осложнений гестационного сахарного диабета у беременных после применения вспомогательных репродуктивных технологий

Aim: to assess the impact of carrying polymorphisms of genes related to lipid and carbohydrate metabolism, vascular tone, and angiogenesis on the complications development related to gestational diabetes mellitus (GDM) in patients with pregnancies resulting from the use of assisted reproductive technology (ART). Patients and Methods: a comprehensive cohort study was conducted. The main group (n=123), comprised of pregnant patients after the use of ART with GDM, was divided into 2 subgroups: 1A — pregnant women with perinatal complications (n=76); 1B — pregnant women without perinatal complications (n=47). The comparison group (n=105) included patients with pregnancies resulting from ART, without GDM. The perinatal complications analyzed in the study included preeclampsia, placental insufficiency, fetal growth retardation, and small for gestational age. Molecular genetic testing was conducted using allele-specific real-time PCR. Polymorphisms of the PPARG (Pro12Ala C&gt;G), TCF7L2 (IVS3 C&gt;T), ApoB Pro2739leu G&gt;A, VEGF-A: -634 G&gt;C, eNOS Glu298Asp G894T G&gt;T genes were studied. Results: carrying the polymorphic Pro12Pro allele of the PPARG gene (Pro12Ala &gt;G) was associated with an increased risk of developing GDM in patients after ART (odds ratio (OR) 2.451, 95% confidence interval (CI) 1.60–3.746, p=0.001). Conversely, the AlaP12Ala allele of the PPARG gene has a protective effect against these risks (OR 0.408, 95% CI 0.267–0.623, p=0.001). It was noted that carrying the TCF7L2 IVS3 TT genotype was associated with an increased risk of developing GDM in patients after ART (OR 3.795, 95% CI 1.482–9.720, p=0.004). Carrying the CC genotype of the VEGF-A -634 G&gt;C gene (OR 3.607, 95% CI 1.084–5.218, p&lt;0.05), as well as the recessive homozygous TT genotype of the eNOS 894 G&gt;T gene (OR 2.637, 95% CI 1.033–6.374; p&lt;0.05), was associated with an increased risk of developing perinatal complications of GDM in patients after ART. Conclusion: identifying genetic determinants of GDM associated with perinatal complications is important for determining the high-risk group at the stage of ART preparation and early pregnancy. Early identification of high-risk patients will allow for effective preventive measures before entry into the program, and for objective analysis of the clinical signs concerning the disease progression, as well as timely correction of carbohydrate metabolism disorders to improve perinatal outcomes. KEYWORDS: ART, gestational diabetes, perinatal complications, gene polymorphisms related to lipid and carbohydrate metabolism, gene polymorphisms — angiogenesis and vascular tone regulators. FOR CITATION: Melkozerova O.A., Murzin A.V., Tretyakova T.B., Deryabina E.G. Molecular-genetic predictors concerning the perinatal complications of gestational diabetes mellitus in pregnant women after assisted reproductive technologies. Russian Journal of Woman and Child Health. 2024;7(1):4–11 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-1.

Предиабет: современные подходы к диагностике и лечению

Aim. To describe modern approaches to the diagnosis and treatment of prediabetes. Key points. Taking into account the growing number of patients with prediabetes, timely diagnosis of this condition is necessary. In case of confirmation of carbohydrate metabolism disorders, active treatment is extremely important already at the stage of prediabetes, the effect on various links of pathogenesis. The management of such patients implies, first of all, an active lifestyle change and a decision on the appointment of drug therapy. When choosing a treatment option for prediabetes, it is important to take into account the type of carbohydrate metabolism disorder. With impaired fasting glycemia, metformin is a more pathogenetically justified option, and with impaired glucose tolerance – Subetta. Conclusion. The substrate, normalizing the indicators of postprandial glycemia and the level of glycated hemoglobin in patients with prediabetes (impaired glucose tolerance), may contribute to reducing cardiovascular risks. However, there are currently no such studies, and therefore it seems relevant to carry out work evaluating the effect of therapy with this drug on the risk of cardiovascular events in patients with prediabetes. Keywords: prediabetes, type 2 diabetes mellitus, impaired fasting glycemia, impaired glucose tolerance, Subetta, metformin.

Incidence of carbohydrate metabolism disorder in iron overload of different etiology

Incidence of carbohydrate metabolism disorder in iron overload of different etiology

Уровень глюкозы, ассоциированный с возникновением новых случаев сахарного диабета 2 типа у мужчин и женщин 45–69 лет в Новосибирске

Aim. What glucose level is associated with the occurrence of new cases of diabetes mellitus 2 type (T2DM). Design. Prospective cohort study. Materials and methods. A survey of a representative sample of Novosibirsk residents was carried out in 2003–2005 as part of the international project Health, Alcohol and Psychosocial factors in Eastern Europe. The presented work included indicators of 3146 people aged 45–69 years without a previous history of carbohydrate metabolism disorders (all individuals with established T2DM at the time of the initial examination were excluded from the analysis). The study included people without a history of diabetes, examined in 2003–2005 and again in 2015–2018. New cases of T2DM were diagnosed in 2003–2021. According to epidemiological criteria, diabetes was established when the fasting blood glucose level was ≥ 7.0 mmol/l, according to the anamnesis and the City Diabetes Registry. Results. Initially, elevated fasting glucose concentrations (5.6–6.9 mmol/l) were detected in 45.3% of participants (28.5% — 5.6–6.0 mmol/l, hyperglycemia 6.1–6.9 mmol/l — 16.8%). According to dynamic observation data, by 2021, 316 (10.1%) people will be diagnosed with T2DM. The threshold blood glucose value that determines the risk of developing T2DM over time is 5.7 mmol/l, Se = 64.2%, Sp = 61.4%, AUC = 0.67. Conclusion. According to our data, among residents of Novosibirsk aged 45–69 years without diabetes, the prevalence of fasting hyperglycemia is high (5.6 mmol/l or more). Glucose level 5.7 mmol/L is the threshold value associated with new cases of T2DM in people 45–69 years of age. Keywords: new cases of type 2 diabetes mellitus, fasting glucose levels, fasting hyperglycemia.

ОСОБЕННОСТИ ГУМОРАЛЬНОГО ИММУННОГО ОТВЕТА У БОЛЬНЫХ С НАРУШЕНИЯМИ УГЛЕВОДНОГО ОБМЕНА В ПОСТКОВИДНОМ ПЕРИОДЕ

Intensive research is currently underway on the impact of the SARS-CoV-2 virus on the human body. One of the often-found consequences of such exposure is endocrine dysfunction. It has been previously shown that the detected hyperglycemia in patients infected with SARS-COV-2 is due to the consequences of direct damage by the SARS-CoV-2 virus, activation of the immune system and inflammation, as well as the consequences of the use of glucocorticosteroids. Changes in adaptive immunity are characteristic of both hyperglycemia and post-COVID syndrome. Of interest is the combination of these conditions, namely, the development of hyperglycemia in the post-COVID period and the resulting humoral immune response. This study is devoted to identifying the features of B-cell immunity in individuals with post-COVID syndrome and disorders of carbohydrate metabolism. The study included 72 people with carbohydrate metabolism disorders in the post-COVID period. In patients, the lymphocytic link of immunity was assessed: the relative and absolute number of B-lymphocytes (CD45+CD19+), B1-lymphocytes (CD45+CD5+CD19-CD27-), B2-lymphocytes (CD45+CD19+CD5-CD27-), general population Memory B cells (CD45+CD19+CD5-CD27+). In post-covid patients with type 2 diabetes mellitus, more significant changes in the B-cell link were revealed in comparison with patients with impaired glucose tolerance, including a statistically significant increase in the number of B-lymphocytes. Also, in the group of patients with type 2 diabetes mellitus, the number of B2-lymphocytes is significantly higher in the absence of differences in the levels of B1-lymphocytes, which is possibly characteristic of the autoimmune nature of the diseases, and is associated with the secretion of high-affinity antibodies, which presumably explains the more severe clinical course of COVID-19 in the study group. At the same time, in patients with type 2 diabetes mellitus, the number of B1- and B2-lymphocytes of memory cells is significantly lower compared to patients with impaired glucose tolerance in the post-COVID period, which suggests the ineffectiveness of the formed immune response, which confirms more frequent repeated cases. COVID-19 in this group of patients.

The Influence of Carbohydrate Metabolism Disorders on the Course of Perioperative Period in Cardiac Surgery Patients with Post-Infarction Left Ventricular Aneurysms

The aim. To study the impact of carbohydrate metabolism disorders on perioperative period in cardiac surgery pa-tients with post-infarction left ventricular (LV) aneurysms.&#x0D; Materials and methods. Retrospective analysis of perioperative period in random 132 patients with post-infarction LV aneurysms of various locations, who were operated on and discharged from the department of surgical treatment of ischemic heart disease of the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. Disorders of carbohydrate metabolism (DCM) were detected in 98 (74.2%) patients, among whom type 2 diabetes mellitus (DM) was diagnosed in 34 (25.7%) patients, impaired glucose tolerance (IGT) in 64 (48.5%). All the patients underwent general clinical examination, electrocardiography, echocardiography, coronary angiography and surgical treatment.&#x0D; Results. When analyzing the clinical picture in patients with post-infarction LV aneurysms, painless myocardial isch-emia was diagnosed in 41 (31.06%) patients, among whom type 2 DM in 11 (26.8%) cases and IGT in 18 (43.9%). No statistically significant difference was found in patients with and without DCM in the LV contractile function, presence of LV thrombosis, atrial fibrillation, chronic kidney disease, stenosis of brachiocephalic arteries and arteries of the lower extremities, gouty arthritis, and body weight. Intraoperatively, diameter of the coronary arteries in patients with type 2 DM was slightly smaller compared to patients without DCM. Its increase in cases of calcification of coronary arteries and aorta among patients of the study group with DCM was statistically insignificant. A careful analysis of the postoperative period in patients with and without DCM showed a statistically significant occurrence of paroxysms of atrial fibrillation in 30 (90.9%) and 3 (9.1%) cases, respectively (p=0.0115). The patients with DCM had longer stay in the intensive care unit: 4.03 ± 2.3 vs. 3.2 ± 1.3 days (p=0.0483). Acute kidney injury in the early postoperative period occurred in 8 (6.06%) patients, including 5 (62.5%) with type 2 DM (p=0.0142). Sternal wound infection occurred in 2 (1.5%) patients with type 2 DM (p=0.0156).&#x0D; Conclusions. Among cardiac surgical patients with postinfarction LV aneurysms, the major part is formed by patients with DCM (74.2%), the presence of which complicates the course of the postoperative period with the development of paroxysms of atrial fibrillation (p=0.0115), acute kidney injury (p=0.0142), sternal wound infection (p=0.0156), a long stay in the intensive care unit (p=0.0483).

Acute kidney injury as a risk factor for atrial fibrillation after coronary artery bypass grafting — effects of sodium-glucose cotransporter-2 inhibitors

Aim. To identify predictors of paroxysmal atrial fibrillation (pAF) in patients with stable angina after coronary artery bypass grafting (CABG), as well as to evaluate the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors.Material and methods. We examined 92 patients with stable angina who received CABG, aged 64±7 years (men, 78,3%). Among this cohort, 81,5% of patients had multivessel coronary artery disease, carbohydrate metabolism disorders — 35,6%, hypertension — 96,7%, chronic kidney disease (CKD) — 23,9%, preprocedural pAF — 10,9%, previous myocardial infarction (MI) — 54,3%. Off-pump CABG was performed in 31,5%, including bilateral inthernal thoracic artery grafting — in 50%. Cardiopulmonary bypass time was 68 (55-83) minutes. The number of grafts was 2,7±0,7. In addition, 18,5% of individuals received SGLT-2 inhibitors. Serum creatinine content was determined by the Jaffe method, and CKD was diagnosed with glomerular filtration rate &lt;60 ml/min. Acute kidney injury (AKI) was assessed according to the KDIGO criteria (2012).Results. The number of patients who had pAF after CABG was 29,3%, AKI — 16,3%. There were following parameters associated with pAF after CABG: creatinine (100;82-142 in patients with pAF and 83;69-105 μmol/l — without pAF, p=0,032) and urea (7,8;5,8-9,7 in patients with pAF and 5,9;4,7-9,1 mmol/l — without pAF, p=0,025) one day after the intervention; postoperative AKI was revealed in 33,3% and 9,2% (p=0,004), while the number of patients taking SGLT-2 inhibitors was 3,7% and 24,6% (p=0,019) in those with and without pAF, respectively. The probability of pAF after CABG increased by an average of 5,5 times with AKI. Patients with pAF after CABG compared to patients without pAF have a higher rate of AKI, intraoperative MI, and cardiac death.Conclusion. The number of patients with pAF after CABG was 29,3%, AKI — 16,3%. Post-CABG pAF predictor was postoperative AKI. The use of SGLT-2 inhibitors was associated with a lower incidence of pAF after intervention. Patients with pAF after CABG have a poor inhospital prognosis.

Study Ocular Hemodynamics in Pregnant Women with Disorders of Carbohydrate Metabolism

Purpose. To study state of ocular hemodynamics in pregnant women with disorders of carbohydrate metabolism using color Doppler imaging. Patients and methods. 147 pregnant women were examined: 40 of them had type 1 diabetes mellitus (DM), 87 had gestational diabetes (GD); in 20 — pregnancy proceeded physiologically. Examination of pregnant women with DM was carried out in each trimester and 3 months after delivery, pregnant women with GD and control groups — once in the third trimester. The parameters of hemodynamics in the central retinal artery (CRA) and in the short posterior ciliary arteries (SPCAs) were studied using color Doppler imaging. Results. It was found that the peak systolic velocity (PSV) in the CRA was significantly lower in the GD and DM groups, while PSV in the SPCAs and end-diastolic velocity (EDV) in the CRA were higher in the control group compared to the GD. In SPCAs, the resistive index (RI) was the highest in the DM group, and the lowest in the GD group. Conclusion. In patients with GD in the third trimester of pregnancy, there is a statistically significant decrease in PSV and EDV in the CRA and SPCAs, combined with a decrease in RI in SPCAs, compared with patients with a physiological course of pregnancy. In patients with diabetic retinopathy (DR) in the third trimester of pregnancy, PSV and EDV in the CRA and SPCAs were significantly lower, and the pulsatility index (PI) and RI were significantly higher compared to pregnant women with DM without DR. In pregnant women with DR during gestation, there was a decrease in PSV and EDV against the background of an increase in RI and PI in the CRA and in the SPCAs. In pregnant women with DM and absence of DR during gestation, there was an increase in PSV, EDV and PI in the CRA and SPCAs from the first to the third trimesters. The revealed features of the state of hemodynamics in the CRA and SPCAs in pregnant women with DM with presence or absence of DR can become the basis for creating criteria for manifestation and progression of DR.

The association of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients with diabetic nephropathy and essential hypertension

Objective — to establish possible associations of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients (pts) with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. Clinical investigation and examinations involved 171 pts, from them 85 (49.7%) females and 86 (50.3%) males with DN of I—IV stages and EH of II—III stages, aged 31 to 82 years old (an average age was 59.38±1.58 years). They were also genotyped for rs4646994 (I/D) ACE and for rs1799983 (G894T) eNOS gene polymorphisms with the use of polymerase chain reaction. Among the patients with I/D polymorphism of ACE gene there were 24 (14.0%) pts with genotype II, 32 (18.7%) pts with genotype ID and 26 (15.2%) subjects with genotype DD. Among the participants with G894T eNOS gene polymorphism GG genotype was revealed in 29 (16.9%) pts, GT genotype was found in 33 (19.3%) cases and 27 (15.8%) examined persons had TT genotype. Standard parameters of lipid profile were measured in all included pts with a use of an immune enzyme method. Glucose oxidase and immune enzyme methods were used to define serum glucose and insulin levels; level of glycosylated hemoglobin (HbA1C) was detected by fluid chromatography method. Insulin resistance (IR) indices such as HOMA‑IR, triglyceride‑glucose index (TGGI), METS‑IR (metabolic score for insulin resistance) index were calculated by known formulas. Cardiometabolic risk (CMR) of the pts was estimated by ­METS‑IR index. Body mass index (BMI), body fat percentage (BFP), total fat mass (TFM) and fat mass index (FMI) in all the pts were calculated by standard known formulas. Serum uric acid concentration was measured with phosphovolframic method. Dapagliflozin 10 mg/daily was added for 24 weeks to the basic standard antidiabetic therapy including gliclazide or glimepiride and metformin combined with lipid lowering therapy containing atorvastatin. The standard therapy was not changed during the whole period of observation.&#x0D; Results. No association has been revealed between I/D ACE and G894T eNOS gene polymorphisms in pts with DN and EH, with a noted improvement of lipid blood spectrum due to administration of dapagliflozin in a dose of 10 mg/daily for 24 weeks. It has been established that allele D was associated with a reduction of dapagliflozin efficacy in the correction of carbohydrate metabolism disorders in pts with DN and EH. At presence of allele D (ID and DD) in genotype, the levels of glycemia, insulinemia, HbA1C, IR indices such as HOMA‑IR, TGGI, METS‑IR decreased less effective than in the case of allele D absence (genotype II). In pts with DN and EH who had G894T eNOS gene polymorphism, dapagliflozin 10 mg/daily improved muscle sensitivity to insulin and decreased CMR depended on genotype in the following order: GT &gt;TT &gt;GG, whereas the intensity of glycemia, insulinemia, HbA1C and HOMA‑IR index reduction was found to be associated with genotype as follows: GG &gt;GT &gt;TT. Allele I compared with allele D of I/D ACE gene polymorphism in pts with DN and EH was revealed to be associated with more significant reduction of BFP, TFM and FMI due to dapagliflozin administration. In pts with DN and EH who had G894T eNOS gene polymorphism dapagliflozin 10 mg/daily reduced a body mass due to its influence on fat accumulation but not on muscle tissue both in phenotype of visceral obesity (genotype GG) and in phenotype of sarcopenic obesity (genotype GT). In the realization of hypouricemic effects of dapagliflozin in patients with DN and EH, both genetic factors (D and T alleles of I/D ACE and G894T eNOS gene polymorphisms correspondingly), and metabolic factors (initial levels of HbA1C and UA together with anthropometric parameters characterized visceral obesity phenotype such as BMI, TFM and FMI) were involved.&#x0D; Conclusions. In pts with DN and EH, the association of I/D ACE (rs4646994) and G894T eNOS (rs1799983) gene polymorphisms with metabolic effects of dapagliflozin 10 mg/daily has been established. A presence of allele D of I/D ACE and allele T of G894T eNOS gene polymorphisms in genotype was concluded to be associated with less significant metabolic effects of dapagliflozin compared with an absence of these alleles in genotype.&#x0D;

IMPACT OF MELATONIN ON SOME INDICATORS OF CARBOHYDRATE METABOLISM IN LIVER OF RATS WITH DEXAMETHASONE-INDUCED DIABETES

One frequently employed experimental model, particularly in pre-clinical studies examining the hypoglycemic effects of potential antidiabetic medications, is the metasteroid diabetes model induced by the prolonged administration of glucocorticoids to animals. This experimental study aimed to elucidate the effects of exogenous melatonin (10 mg/kg) on glycogen content and the activity of key enzymes—pyruvate kinase (PK) [EC 2.7.1.40], lactate dehydrogenase (LDH) [EC 1.1.1.27], glucose-6-phosphate dehydrogenase (G-6-PDH) [EC 1.1.1.49], and glucose-6-phosphatase (G-6-P-ase) [EC 3.1.3.9]—in the livers of rats with dexamethasone-induced diabetes. Materials and Methods. The experiments were performed on 44 male 18-month-old white non-linear rats, divided into three groups: 1) control (intact rats), 2) rats with dexamethasone-induced diabetes, 3) rats that amid the progression of dexamethasone-induced diabetes, underwent daily oral administration of melatonin (Sigma, USA) in a dose of 10 mg/kg. Dexamethasone diabetes was modeled by subcutaneous injection of dexamethasone (injection solution 4 mg/ml, KRKA, Slovenia) at a dose of 0.125 mg/kg body weight daily for 13 days (O.V. Stefanov, 2001). Decapitation of animals was carried out in accordance with the norms of the "European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes" (Strasbourg, 1986). Glucose content in blood from the tail vein of rats, taken on the 14th day of fasting before decapitation of the animals, was determined using a portable glucometer (One Touch Ultra Easy, Life Scan, USA). The content of glycogen and the activity of the studied enzymes of carbohydrate metabolism in the liver were determined according to the generally accepted, previously described methods. A 5% homogenate was prepared from the cold-isolated rat liver in a chilled 50 mM Tris-HCI buffer (pH=7.4) to study the activities of pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in the cytosolic fraction. The reliability of the difference between the obtained indicators was assessed using the parametric Student's t-test (for normal distribution) and the non-parametric Mann-Whitney U-test (for non-normal distribution). Differences were considered probable at p≤0.05. Results and discussion. According to our results, in the liver of diabetic rats that did not receive any means of correction of carbohydrate metabolism disorders, the glycogen content was 33% lower than in intact animals. The activities of enzymes such as pyruvate kinase and glucose-6-phosphate dehydrogenase were also reduced in the liver of rats with impaired glucose tolerance by 31.6 and 21.5%, respectively, compared to intact animals, indicating inhibition of glucose oxidation pathways, both at the level glycolysis (decrease of pyruvate kinase), as well as at the level of the oxidative stage of the pentose-phosphate pathway of glucose-6-phosphate oxidation. At the same time, the activity of lactate dehydrogenase and especially glucose-6-phosphatase in the liver of rats with diabetes by 19.5 and 56%, respectively, exceeded the indicators of animals of the control group, which demonstrates the increased activity, intensity of glycogenolysis and gluconeogenesis under conditions of insulin resistance, because glucose-6-phosphatase is the terminal enzyme of these processes. Regarding the investigated parameters of carbohydrate metabolism, both the glucose content in the blood of rats, as well as the glycogen content and the activity of all studied enzymes in the liver of rats that were injected with melatonin against the background of the development of diabetes, did not reliably differ from the parameters of intact animals, which confirms the assumption of the probable hypoglycemic effect of melatonin against the background of the development of diabetes. Conclusions: The daily two-week use of melatonin (10 mg/kg), against the background of the development of dexamethasone diabetes in rats, contributes to the normalization of certain indicators of carbohydrate metabolism in the liver of animals.

Management peculiarities of patients with hyperprolactinemia in case of mass formations of the hypothalamic-pituitary region: a clinical case

Hyperprolactinemia is a condition characterized by persistently elevated blood prolactin level. The most prominent manifestations of it are reproductive dysfunction, as well as fat and carbohydrate metabolism disorders, including body weight gain, dyslipidemia, impaired glucose tolerance, and insulin resistance. We describe here a case of hyperprolactinemia in a young man and perform differential diagnosis of prolactinoma with craniopharyngioma. The article demonstrates that initiation of treatment with dopamine agonists allows us to make a correct diagnosis and to determine optimal tactic of management – either therapy or surgery.

Evaluation of antiobesity activity of justicia tranquebariensis on progesterone-induced obese rats

Obesity is characterized as abnormal or excessive fat deposition in adipose tissue and is a chronic disorder of carbohydrate and fat metabolism and poses a risk to the health and well-being of humans. Natural herbal products for weight reduction may be effective in the treatment of obesity and associated disorders. Therefore, the present study was to investigate the phytochemical screening, anti oxidant and anti-obesity activity of Justicia tranquebariensis extract. The phytochemical screening Justicia tranquebariensis showed that the presence of saponins, flavonoids, steroids, terpenoids, polyphenol, and alkaloids in ether, ethanol and aqueous extracts. Quantitative analysis of phenol and flavonoids was carried out. Significant amount of flavonoids and phenols were present. The anti-obesity activity of Justicia tranquebariensis was proved by inhibition of lipase. Overall, it was concluded from the present study that Justicia tranquebariensis extract possesed rich source of phytochemicals and hence anti-obesity activity.

Disorders of carbohydrate metabolism and candidate genes for the pathophysiology of polycystic ovary syndrome. A literature review

Polycystic ovary syndrome is a common heterogeneous disease with metabolic disorders. In the last decade, the study of polycystic ovary syndrome pathogenesis has been associated with the modern development of molecular genetics, transcriptomics, and sequencing methods. Numerous studies have shown that the study of genetic markers and epigenetic changes in metabolic disorders, oxidative stress, chronic inflammation, and mitochondrial dysfunction in polycystic ovary syndrome is an important direction in the pathogenesis and etiology of the disease. The aim of this literature review was to describe candidate genes involved in the pathophysiology of polycystic ovary syndrome and associated with disorders of carbohydrate metabolism according to modern domestic and foreign literature over the past five years. The candidate gene data presented were assessed based on the main aspects of polycystic ovary syndrome pathophysiology, namely, metabolic dysfunction, androgen and gonadotropin imbalance, and inflammation. The insulin genes (variable number of tandem repeats), such as INS-VNTR, IRS-1, IRS-2, and INSR, adiponectin and calpain-10 genes, as well as CY1A1, CYP11A1, PON1, DENND1A and TCF7L2 genes are associated with metabolic disorders in polycystic ovary syndrome. Genetic variants of genes involved in regulating the expression and mechanism of action of insulin, as well as its receptors and substrates (IRS-1, IRS-2, INSR), have been suggested as possible factors involved in the development and severity of the clinical and metabolic manifestations of polycystic ovary syndrome. The presented data on PPARγ gene (and its coactivator PGC-1α) expression levels in women with polycystic ovary syndrome revealed the presence of PPARγ gene polymorphisms associated with insulin resistance. Thus, the data presented in this review from genome-wide association studies (GWAS) and the study of candidate genes showed that numerous pleiotropic effects cause carbohydrate metabolism disorders in polycystic ovary syndrome. The study of genetic markers and epigenetic changes in the development of metabolic disorders, oxidative stress, chronic inflammation, and mitochondrial dysfunction in polycystic ovary syndrome is an important direction in the pathogenesis of the disease.

Влияние сахарного диабета на когнитивные функции в детском и подростковом возрасте

Type 1 diabetes mellitus (DM1) is widespread among children and adolescents in Russia. In addition to the pretty well-studied microvascular complications of the disease, scientific sources also describe the brain damage that is manifested by cognitive impairment. Despite the problem being studied actively by researchers Worldwide, they have reported mixed and sometimes contractionary results. Thus, as of now there are disputes about the etiology, pathogenesis, clinical manifestations and factors affecting the development of the abovementioned complications. Changes in the brain are registered at all age periods with special attention being fairly paid in childhood and adolescence because such disorders of carbohydrate metabolism during active growth can lead not only to functional, but also to structural changes in the brain. This is manifested by memory impairment and decreased attention concentration, which in its turn negatively affects the academic performance of schoolchildren and therefore reduces the quality of life of patients. Further study of this problem would help developing an algorithm for early diagnosis of cognitive impairment among children and adolescents with DM1 in order to increase compliance among patients, reduce the risk of microvascular complications and possible disability in older age. A promising direction in the diagnosis of cognitive disorders are neuroimaging methods, which, as opposed to neuropsychological tests, are helping to identify morphofunctional changes in the brain. This bibliographical review describes the etiology of cognitive disorders in children and adolescents with DM1, the main variants of cognitive dysfunction, the effect of the disease on schooling performance and neuroimaging disorders of the brain.

RISK FACTORS FOR THE DEVELOPMENT OF CARDIOVASCULAR DISEASES IN ADOLESCENTS IN YAKUTSK, SAKHA REPUBLIC (YAKUTIA)

The article presents data on the frequency of risk factors for cardiovascular diseases in adolescents. A statistical analysis was also conducted to determine the correlations between the risk factors when an individual has multiple risk factors. The following risk factors for cardiovascular diseases, already occurring frequently in adolescence, were evaluated: high blood pressure, overweight, elevated cholesterol levels, carbohydrate metabolism disorders, low physical activity, eating disorders, and stress perception. A total of 712 adolescents aged 15 –16 years were examined, including 360 girls and 352 boys, residing in the city of Yakutsk, Sakha Republic (Yakutia). The study revealed that among adolescents, low physical activity showed the highest frequency among the risk factors, followed by others in descending order: restrictive eating behavior, high cholesterol and glucose levels, overweight and obesity, and high stress perception. The differences found were based on gender, with boys being more susceptible to obesity. Correlation analyses using Spearman’s (rs) and Pearson’s (rp) coefficients and Pearson’s chi-square test were used to identify relationships between risk factors for cardiovascular diseases. The analysis showed that high blood pressure is associated with adolescents who have high body mass index. Gender-based analysis showed that girls are more prone to arterial pressure disorders and elevated cholesterol and glucose levels.

Novel food isolates with striking α-glucosidase inhibitory activity and probiotic potential for an antidiabetic role.

In the current study, ten lactic acid bacteria (LAB) isolates exhibiting anti-α-glucosidase activity were isolated from fermented food. It is directed at novel supplementary diets to prevent/improve diet-induced carbohydrate metabolism disorders and related chronic diseases. Moreover, to evaluate their safety, functionality, and probiotic potential via in vitro simulated test conditions. From 16s-rRNA sequencing, Pediococcus acidilactici (NKUST 803, 845, 858), Lactobacillus plantarum (NKUST 817, 828, 851), Levilactobacillus brevis (NKUST 816, 855) and Lactobacillus acidophilus (NKUST 803, 863) were identified. The results showed that the isolates possessed anti-pathogenic activity, auto-aggregation ability, hydrophobicity (47.44-96.4%), and gastric acid-resistant activity (79-99.1%), which proved their potential for probiotics in nutraceuticals to render hypoglycemic activity or antidiabetic effects to the host positively. Among tested isolates, L. plantarum 817 and P. acidilactici 858 exhibited maximum α-glucosidase inhibitory (AGI) activity of 35-40%. The heat map clearly showed that L. plantarum 817 exhibited the best AGI activity and probiotic potential, among others. These were studied under various simulated gut conditions and safety tests. However, all isolates possess the potential to be used as probiotics in commercial-scale health applications. Pediococcus sp. possesses notable AGI activity but relatively less colonization potential in the gut hence recommended daily intake for positive health effects.