Carbohydrate Metabolism Disorders Research Articles

МУЛЬТИДИСЦИПЛИНАРНЫЙ ПОДХОД К ДИАГНОСТИКЕ И ЛЕЧЕНИЮ ИНФЕКЦИОННЫХ ОСЛОЖНЕНИЙ СИНДРОМА ДИАБЕТИЧЕСКОЙ СТОПЫ

Introduction. Diabetic foot syndrome is one of the severe complications of diabetes mellitus. This combination of pathological processes occurring in the foot is induced and aggravated by diabetes mellitus. Most often, diabetic foot syndrome is a consequence of angiopathy, neuropathy, osteopathy; it may be accompanied by infectious and ulcera-tive lesions, leading to amputation of the extremity. The aim of the study. To assess the results of diagnosis and treatment of diabetic foot syndrome, following the intro-duction of a multidisciplinary approach. Materials and methods. A retrospective analysis of 151 medical records of patients diagnosed with diabetic foot syndrome was carried out. There were 87 (57.6 %) men and 64 (42.4 %) women; the mean age was 63.6 ± 1.0 years. The most of patients (139 (92.1 %)) were diagnosed with type 2 diabetes mellitus. Results. A multidisciplinary approach to the diagnosis and treatment of diabetic foot syndrome was achieved through the efforts of a team of specialists consisting of a surgeon, general practitioner, endocrinologist and vascular surgeon. The average glycemic level in the examined patients was higher than normal and amounted to 10.6 ± 0.4 mmol/l. In 111 of patients, the correction of carbohydrate metabolism was carried out with insulin, in the remaining observations – with tableted hypoglycemic drugs. All patients received treatment aimed at eliminating the main links in the pathogenesis of diabetic foot syndrome. Local conservative treatment was carried out in 66 cases, surgical treatment – in 85 cases. The majority of surgical interventions (40–47 %) were minor surgeries (preserving the supporting function of the leg), in 20 (23.5 %) patients surgeries were performed on the arteries, in 19 (22.4%) – high amputations (above the ankle joint), in 6 (7.1 %) – opening of foot phlegmon. The average duration of treatment for diabetic patients with diabetic foot syndrome was 17.1 ± 0.6 days. Conclusion. Patients with diabetic foot syndrome were diagnosed with severe disorders of carbohydrate metabolism with the presence of angiopathy and neuropathy. A multidisciplinary approach to the diagnosis and treatment of diabetic foot syndrome makes it possible to identify the main links in pathogenesis and, based on existing protocols, to per-sonalize the treatment. This makes it possible to preserve the supporting function of the extremity in most patients and to reduce the number of high amputations.

РЕДКИЙ СЛУЧАЙ ОБТУРАЦИОННОЙ КИШЕЧНОЙ НЕПРОХОДИМОСТИ: ТОНКО-ТОЛСТОКИШЕЧНАЯ ИНВАГИНАЦИЯ У ВЗРОСЛОГО

Introduction. Diabetic foot syndrome is one of the severe complications of diabetes mellitus. This combination of pathological processes occurring in the foot is induced and aggravated by diabetes mellitus. Most often, diabetic foot syndrome is a consequence of angiopathy, neuropathy, osteopathy; it may be accompanied by infectious and ulcera-tive lesions, leading to amputation of the extremity. The aim of the study. To assess the results of diagnosis and treatment of diabetic foot syndrome, following the intro-duction of a multidisciplinary approach. Materials and methods. A retrospective analysis of 151 medical records of patients diagnosed with diabetic foot syndrome was carried out. There were 87 (57.6 %) men and 64 (42.4 %) women; the mean age was 63.6 ± 1.0 years. The most of patients (139 (92.1 %)) were diagnosed with type 2 diabetes mellitus. Results. A multidisciplinary approach to the diagnosis and treatment of diabetic foot syndrome was achieved through the efforts of a team of specialists consisting of a surgeon, general practitioner, endocrinologist and vascular surgeon. The average glycemic level in the examined patients was higher than normal and amounted to 10.6 ± 0.4 mmol/l. In 111 of patients, the correction of carbohydrate metabolism was carried out with insulin, in the remaining observations – with tableted hypoglycemic drugs. All patients received treatment aimed at eliminating the main links in the pathogenesis of diabetic foot syndrome. Local conservative treatment was carried out in 66 cases, surgical treatment – in 85 cases. The majority of surgical interventions (40–47 %) were minor surgeries (preserving the supporting function of the leg), in 20 (23.5 %) patients surgeries were performed on the arteries, in 19 (22.4%) – high amputations (above the ankle joint), in 6 (7.1 %) – opening of foot phlegmon. The average duration of treatment for diabetic patients with diabetic foot syndrome was 17.1 ± 0.6 days. Conclusion. Patients with diabetic foot syndrome were diagnosed with severe disorders of carbohydrate metabolism with the presence of angiopathy and neuropathy. A multidisciplinary approach to the diagnosis and treatment of diabetic foot syndrome makes it possible to identify the main links in pathogenesis and, based on existing protocols, to per-sonalize the treatment. This makes it possible to preserve the supporting function of the extremity in most patients and to reduce the number of high amputations.

Hospital complications in patients with acute kidney injury after coronary artery bypass grafting

The aim was to assess the incidence of hospital complications in patients with acute kidney injury (AKI) after coronary artery bypass grafting (CABG).Patients and Methods. The study included 77 patients with stable angina who underwent CABG, aged 65 (61-69) years, 77,9 % men. The number of patients with arterial hypertension was 96,1 %, with carbohydrate metabolism disorders 45,5 %, with chronic kidney disease (CKD) 22,1 %, and with myocardial infarction (MI) 57,1 %. CABG on the working heart was performed in 28,6 %, bimammary CABG in 49,4 %. The duration of artificial circulation was 64 (55-82) minutes; the number of shunts implanted was 2,7+0,7 units. CKD was diagnosed when the glomerular filtration rate was less than 60 ml/min. The development of AKI was assessed according to the KDIGO criteria (2012).Results. CABG related AKI was detected in 10 (13 %) patients, of which grade 1 in 9 (11,7 %), grade 2 in 1 (1,3 %). The indicators associated with AKI after CABG were more severe initial CKD (stages 3b and 4 CKD – 20 % vs 1,5 %, p=0,043), a higher incidence of acute heart failure (in terms of adrenaline requirement – 30 % vs 5,9 %, p=0,043), more occluded coronary arteries (in the groups with and without CABG: one occlusion 70 % and 52,2 %, two occlusions 0 % and 13,4 %, three occlusions 10 % and 0 %, respectively, p=0,028). More severe CKD (stages 3b and 4) statistically significantly increased the relative risk of AKI after CABG by an average of 2,9 times. Among patients with AKI compared to patients without AKI after CABG, there was a higher incidence of cardiac death (20 % vs 0 %, p=0,015), intraoperative MI (60 % vs 8,9 %, p=0,001), acute heart failure (30 % vs 5,9 %, p=0,043).Conclusion. The incidence of AKI following CABG was 13 %. The development of AKI was associated with more severe initial CKD. Patients with postoperative AKI had a poor hospital prognosis.

PREVENTION OF TYPE 2 DIABETES MELLITUS

Prevention of type 2 diabetes mellitus and complications is an urgent problem in modern medicine. In patients with a body mass index (BMI) above 25 kg/m2, indicators of markers of carbohydrate metabolism (serum glucose -fasting and postprandial glycemia, glycosylated hemoglobin and urine glucose) and lipid metabolism -total cholesterol (TC), triglycerides (TG), lipidogram (low-density lipoprotein cholesterol -LDL cholesterol, atherogenic index -AI is significantly higher, and high-density lipoprotein cholesterol -HDL cholesterol is significantly lower than in patients with normal body mass index (BMI) and abdominal index (AI). Asignificant positive relationship between age, abdominal index, BMI, AI, glucose level in blood serum. Assessment of markers of carbohydrate and lipid metabolism should be included in the list of mandatory examinations of patients over the age of 30 years, and be strictly individual. There is a relationship between the progression of carbohydrate metabolism disorders and changes in lipid parameters metabolism in the examined women.The population should be widely informed about the development of type 2 diabetes mellitus and the progression of complications.

Quality of Life of Patients with Hypertensive Disease and Type 2 Diabetes mellitus and Its Parameters Depending on Plasma Catestatin and Relaxin-2 Levels

The objective: to investigate the impact of hypertensive disease (HD) and concomitant type 2 diabetes mellitus (T2DM) on the quality of life (QOL) of patients using the SF-36 questionnaire and to evaluate the peculiarities of the QOL parameters depending on plasma relaxin-2 (RLN-2) and catestatin (CTS) levels. Materials and methods. The study was conducted in accordance with the principles of the Declaration of Helsinki. 136 patients took part in the study: 106 patients with HD and 30 healthy volunteers. The patients with HD were divided into two groups. The first group included 55 patients with HD and T2DM, the second group – 51 persons with HD without T2DM. Each study participant underwent a comprehensive clinical, laboratory and instrumental examinations. All participants filled out quality of life SF-36 questionnaire and the questionary of HD patient. Concentrations of CTS and RLN-2 in blood plasma were determined by enzyme immunoassay method (E4996Hu, BT Lab, Shanghai, China and E-EL-H1582, Elabscience, USA, respectively). All patients filled the home blood pressure monitoring diaries for 31 days. Statistical data analysis was performed using the SPSS 25.0 statistical program. Results. The patients with HD had lower parameters of physical and mental components of health compared to healthy volunteers (p<0.005). It was found that the presence of concomitant T2DM leads to even a greater decrease in quality of life indicators than in patients with HD without carbohydrate metabolism disorders (p<0.05). In patients with RLN-2 levels ≥4.69 pg/ml the lower parameters of the physical component of health (p<0.05) and social functioning (p=0.012) were determined. Lower CTS scores are associated with lower QOL scores (p≤0.005). Significant negative correlations were found between average SBP (aSBP) and indicators of physical and mental components of health (p<0.001), while mean DBP had correlations only with general health and total physical component of health (p<0.05). Conclusions. HD leads to a decreased QOL of patients, which is confirmed by lower scores of the SF-36 questionnaire and established negative correlations between aSBP and QOL parameters. The presence of concomitant T2DM is associated with even a greater decline in physical and mental health components.

Biomarkers and subclinical left ventricular dysfunction in patients with type 2 diabetes without clinical manifestations of cardiovascular diseases

Aim. To study the relationship between the structural and functional left ventricular (LV) parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with type 2 diabetes (T2D) without clinical manifestations of cardiovascular diseases, as well as to evaluate the possibility of their use for early diagnosis of subclinical LV dysfunction.Material and methods. Data from 120 patients of both sexes aged 45-75 years (57,11±7,9 years) were analyzed. They were divided into three following groups: 1st — with T2D (n=47), 2nd — with prediabetes (n=20), 3rd — control (n=53). All participants underwent transthoracic echocardiography with assessment of the linear and volumetric heart dimensions, systolic and diastolic LV function. Speckle tracking echocardiography was analyzed with calculation of LV global longitudinal strain (GLS). The blood levels of NT-proBNP and inflammatory markers were determined (high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6).Results. According to echocardiography, patients with carbohydrate metabolism disorders revealed significantly higher LV mass values, LV posterior wall thickness, and relative wall thickness in comparison with the control group. Transmitral flow parameters, as well as tissue Doppler sonography, in the T2D and prediabetes groups were significantly different from those in the control group. GLS in the groups of patients with carbohydrate metabolism disorders was lower than in the control group (p=0,001). The level of NT-proBNP was significantly higher in the T2D and prediabetes groups compared to the control group, while in all three groups it did not exceed normal values (p<0,001). A higher level of NT-proBNP was associated with hypertension — odds ratio (OR) 3,64 [1,02-13,04] (p=0,005), a decrease in LV ejection fraction — OR 1,25 [1,06-1 ,47] (p=0,007), concentric hypertrophy — OR 4,84 [1,43-16,41] (p=0,011) and decreased GLS — OR 1,85 [1,62-2,06] (p=0,005), an increase in the ratio of early and late diastolic transmitral flow (E/A) — OR 0,01 [0,008-0,416] (p=0,024) and isovolumic relaxation time (IVRT) — OR 1,08 [1,03-1,14] (p=0,03). The sensitivity and specificity of NT-proBNP as a test for predicting GLS reduction <-18% were 86 and 27%, respectively. The hsCRP level, within the reference values, was significantly higher in the T2D and prediabetes groups compared to the control group (p<0,001) and demonstrated a direct linear relationship with E/A, IVRT, early diastolic deceleration time (p<0,05). A higher level of hsCRP was significantly associated with diastolic dysfunction — OR 1,16 [1,02-1,32] (p=0,023), as well as with a GLS decrease <-18% — OR 1,58 [1,12-4,65] (p=0,03).Conclusion. In patients with T2D without clinical manifestations of cardiovascular disease, the presence of concentric LV myocardial hypertrophy, LV diastolic dysfunction and decreased GLS (<-18%) is associated with higher blood levels of NT-proBNP and hsCRP. However, in all cases, the levels of biomarkers do not exceed the reference values, which does not allow their use in the early diagnosis of subclinical LV dysfunction in T2D.

Gestational diabetes – management strategies including pharmacological treatment and lifestyle interventions

Diabetes is a chronic disease, characterized by elevated blood glucose levels, resulting from insulin resistance and inadequate insulin production. Among many types of diabetes, gestational diabetes (GDM) is a unique kind, correlated with numerous metabolic changes occurring during pregnancy, it develops around second trimester of the gestation and in most cases resolves after delivery. The prevalence of gestational diabetes is rising globally and becomes a significant public health concern. [48] According to the World’s Health Organization’s classification GDM is, apart from the diabetes mellitus type 1 (DM1) and diabetes mellitus type 2 (DM2), one of the main clinical forms of carbohydrate metabolism disorders occurring during pregnancy. So far, epidemiological data are ambiguous regarding GDM prevalence, this study estimates GDM frequency at 4–12%. [1] The aim of this article is to provide a comprehensive analysis of the topic of gestational diabetes, its prevalence, risk factors, importance of early detection, methods of glycemia monitoring and management strategies, including lifestyle interventions and pharmacological treatment. Referring to the treatment, it also describes the preparation for pregnancy of people with preexisting DM1 and DM2 and the necessity to modify foregoing management strategies. Furthermore, it describes the most frequent early complications resulting from GDM as well as long-term outcomes for both mother and offspring.

Hubungan Tingkat Pengetahuan dan Sikap Terkait Diabetes Melitus dengan Kadar Glukosa Darah Sewaktu (GDS) Lansia di Wilayah Puskesmas Tanggulangin

Diabetes mellitus (DM) was a metabolic disease characterized by an increase in blood glucose levels accompanied by a decrease in carbohydrate, protein and fat metabolism. The elderly group (elderly) was the group most at risk of developing dm because this group was a population that was susceptible to carbohydrate metabolism disorders which could lead to diabetes mellitus. This studied aims to analyze the relationship between the leveled of knowledge and attitudes regarding dm on the blood sugar levels of the elderly. This researched used an observational studied with a crossed sectional approached. The population in this studied was members of the elderly posyandu in the working area of the tanggulangin community health center used a random sampling technique of 88 respondents. Data collection used knowledge questionnaires and attitude questionnaires. Data was analyzed used univariate analysis and bivariate analysis (chi square test). The results of the analysis showed that the leveled of knowledge (p=0,011) and attitudes of the elderly (p=0,008) regarding diabetes mellitus showed a significant relationship (p<0,05)

Alginate-Based Carriers Loaded with Mulberry (Morus alba L.) Leaf Extract: A Promising Strategy for Prolonging 1-Deoxynojirimicyn (DNJ) Systemic Activity for the Nutraceutical Management of Hyperglycemic Conditions.

The iminosugar 1-deoxynojirimicyn (DNJ) contained in mulberry leaves has displayed systemic beneficial effects against disorders of carbohydrate metabolism. Nevertheless, its effect is impaired by the short half-life. Alginate-based carriers were developed to encapsulate a DNJ-rich mulberry extract: Ca-alginate beads, obtained by external gelation, and spray-dried alginate microparticles (SDMs). Mean size and distribution, morphology, drug loading, encapsulation efficiency, experimental yield, and release characteristics were determined for the two formulations. Ca-alginate beads and SDMs exhibited an encapsulation efficiency of about 54% and 98%, respectively, and a DNJ loading in the range of 0.43-0.63 μg/mg. The in vitro release study demonstrated the carriers' capability in controlling the DNJ release in acid and basic conditions (<50% in 5 h), due to electrostatic interactions, which were demonstrated by 1H-NMR relaxometry studies. Thus, alginate-based particles proved to be promising strategies for producing food supplements containing mulberry leaf extracts for the management of hyperglycemic state.

Association of Polymorphic Variants of TCF7L2 and PPARG Genes with Metabolic Markers in Patients with Early Disorders of Carbohydrate Metabolism.

We performed complex analysis of the association of polymorphic variants rs7903146 of the TCF7L2 gene and rs1801282 of the PPARG gene with metabolic parameters, insulin resistance, and β-cell function in a group of patients with early signs of carbohydrate metabolism disturbances in a sample of Tyumen citizens. The study group consisted of 64 people (39 women, 25 men) aged 40-70 years. The distribution of frequencies of alleles and genotypes of the polymorphic markers rs7903146 and rs1801282 was analyzed and associations of carriage of major homozygous polymorphisms with various phenotypic traits were identified. Genotyping for polymorphic variants of TCF7L2 and PPARG genes was performed using allele-specific PCR with primers provided by Synthol company. Carriers of homozygotes for allele C of the polymorphic marker rs7903146 significantly differed from other respondents by a higher level of C-peptide, as well as by the presence of associations with waist circumference, elevated level of glycated hemoglobin, and arterial hypertension. Carriers of homozygotes for the allele C of the rs1801282 polymorphism of the PPARG gene differed from the group of carriers of homozygotes for the allele G and the group of heterozygote carriers by higher levels of triglycerides, as well as the presence of associations with waist circumference and the level of glycated hemoglobin.

1166A&gt;C polymorphism of the &lt;i&gt;AGTR1&lt;/i&gt; gene as a marker metabolic disorders in the North residents

BACKGROUND: dyslipidemia is currently considered to be one of cardiovascular risk factors. Angiotensin II receptor type I (AGTR1) genetic polymorphisms are known as candidate genes for hypertension, diabetes, as well as for diabetes and obesity complications. Until now, there are not much data on how 1166A&gt;C (rs5186) polymorphism of the AGTR1 gene correlates with Northerners’ carbohydrate and lipid metabolism disorders. In addition, the data are contradictory. Following on from this, we see it is relevant to study the subject.AIM: this research assessed variants of 1166A&gt;C (rs5186) polymorphism of the AGTR1 gene as a predictor of dyslipidemia, carbohydrate metabolism disorders, overweight, and hypertension.MATERIALS AND METHODS: the North residents from Magadan Region, Caucasian by ethnicity, aged from 24 to 56 (average age 43.7± 1.4 yrs) participated in the survey. By real-time polymerase chain reaction we determined the single nucleotide polymorphism of the AGTR1 (rs5186) gene. We also analyzed physical development and cardiovascular variables as well as the concentrations of glucose, insulin, glycosylated hemoglobin, C-reactive protein, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The insulin resistance index and the atherogenicity coefficient were calculated using standard methods.RESULTS: the examined subjects were one hundred and one volunteers. According to the results of genetic analysis, 55 people were assigned to the group of homozygotes for the wild type (AA) and 46 people were assigned to the group of the AGTR1*C allele variant carriers (heterozygotes and homozygotes AC+CC). Our findings contributed to the evidence on more unfavorable lipid pictures showed by the AGTR1*C allele variant carriers: significantly high values of total cholesterol (5,77±0,11, р=0.045), low-density lipoproteins (3,87±0,09, р=0.009), triglycerides (1,43±0,06, р=0.035), and atherogenicity coefficient (3,61±0,10, р=0.001), along with significantly low values of high-density lipoproteins (1,30±0,03, р=0,008). The above indicators were observed as opposed to significantly high fasting glycemia (5,74±0,14, р=0.006) and glycosylated hemoglobin (5,74±0,09, р=0.001) exhibited by the AA homozygotes subjects whose indices could be defined as the state of prediabetes. No intergroup differences were found in anthropometric or cardiovascular variables.CONCLUSION: thus, we could see impairments in the lipid pictures of the AGTR1*С polymorphic variant carriers along with the optimization of carbohydrate metabolism and no effect on the blood pressure or anthropometric characteristics.

Polypragmasy and the basics of personalized rational pharmacotherapy selection in older patients with obesity and type 2 diabetes mellitus

Increasing life expectancy and, as a consequence, a large number of comorbidities lead to a multitude of medications prescribed by physicians of different specialties. Patients with obesity and carbohydrate metabolism disorders, especially with type 2 diabetes mellitus (DM2), are at particular risk of polypragmasy, which is associated with the use of potentially nonrecommended medications. Prescribing errors can cause significant harm to the patient’s health and increase the risk of rehospitalization and healthcare costs. Identification of probably not recommended drugs in this category of patients will improve understanding of prevalence and risk factors of their use, develop strategies to prevent and limit the burden of taking inappropriate drugs and promote development of personalized and patient-oriented treatment options. Tools exist to assess potentially inappropriate therapy (PIT) in the elderly and new tools and criteria are often created. However, they are not specifically aimed at people with obesity and carbohydrate metabolism disorders. Thus, these criteria usually include only a few items related to DM2. Consequently, there is a clear need for a modern tool that can be used to address PIT specifically in older adults with obesity and carbohydrate metabolism disorders.

Pregnancy course and outcomes in patients with non-insulin dependent gestational diabetes mellitus: An observational cohort study

Background. Gestational diabetes mellitus is the most frequent metabolic disorder during pregnancy. Its prevalence is steadily increasing worldwide. In the setting of hyperinsulinism, this pathology may cause various structural and functional changes in the placenta, as well as a reduction in oxygen supply to the fetus. This may result in fetal hypoxia and increased risk of fetal growth restriction. Therefore, research into the specific features of gestation course in patients with gestational diabetes mellitus in order to prevent its complications appears relevant. Objective. To study the specific features of gestation, delivery, and perinatal outcomes in patients with non-insulin dependent gestational diabetes mellitus. Methods. We conducted an observational cohort study of the case histories of 120 women with singleton pregnancies of the second and third trimesters with diagnosed non-insulin dependent gestational diabetes mellitus, their labor and delivery records, and the medical records of the newborns. All the patients were managed at the Ural Research Institute of Maternity and Child Care during 2021–2023. The main group comprised 70 patients whose pregnancy was complicated by sub- and decompensated forms of placental insufficiency. The comparison group comprised 50 pregnant women without pathologies of the fetoplacental complex. The obstetric history, gestation course of the present pregnancy and its outcomes, as well as the condition of the newborns, were analyzed. The obtained data were processed by the methods of variation statistics using Microsoft Excel spreadsheets (Microsoft, USA) and Statistica 13 (DellInc., USA) and MedCalc 15.8 (MedCalcSoftware, Belgium) applications. The null hypothesis was rejected at p &gt; 0.05. Results. Gestational diabetes mellitus in previous pregnancies was statistically significantly less frequent in the main group (2.9% (n = 2)) than in the comparison group (18.0% (n = 9)) ( p &gt; 0.05). Placental insufficiency in the main group was characterized by fetal growth restriction, which was associated with impaired uteroplacental blood flow in 58.6% (n = 41) of the cases. In the main group, the pregnancy ended in preterm delivery in 21.4% (n = 15) of the cases; in 78.6% (n = 55) of the cases, the delivery was at term. There were no preterm births in the comparison group, p &gt; 0.05. Cesarean section was performed in 62.9% (n = 44) of patients in the main group, compared to 20.0% (n = 10) in the comparison group ( p &gt; 0.05). Newborns of the main group required respiratory support more often (p &gt; 0.05). Conclusion. The mechanism of placental insufficiency in patients with non-insulin dependent gestational disorders of carbohydrate metabolism remains to be elucidated. Further research should investigate the predictors of fetoplacental complex pathologies in this group of patients in order to reduce the number of perinatal complications.

Physiology and pharmacology of glucagon-like peptide-1 receptor

Modern approaches to the treatment of type 2 diabetes mellitus (T2DM) are aimed not only at glycemic control, but also at reducing cardiovascular risks. The increasing prevalence of the disease and the need for effective treatment options highlight the importance of glucagon-like peptide-1 (GLP-1) receptor agonists in the pharmacotherapy structure.The aim of the work was to review the literature regarding the physiology of GLP-1 and the therapeutic potential and development trends of its agonists.Materials and methods. The search for the review materials was carried out using the abstract databases of PubMed, Google Scholar and e-Library. The search was carried out for publications from 2000 to 2023, using the following keywords: “GLP-1”; “GLP-1R agonists”; “GIP”; “exenatide”; “liraglutide”; “dulaglutide”; “semaglutide”; “lixisenatide”; “albiglutide”; “taspoglutide” taking into account various spellings.Results. The interaction of almost all food components with enteroendocrine cells of the intestine leads to the secretion of incretins (primarily GLP-1) into the blood, triggering a complex of physiological reactions aimed primarily at the rapid utilization of incoming glucose (regulation of insulin and glucagon secretion), as well as the central regulation of dietary behavior (slowing gastric emptying and the formation of a feeling of satiety). A wide distribution of the GLP-1 receptor in various tissues and organs, its connection with intracellular signaling cascades aimed at launching energy-consuming remodeling (recovery) processes in endothelial cells, heart, neurons, beta cells, etc., is the basis for a wide range of pleiotropic effects of GLP-1 unrelated to its hypoglycemic effect. The discovery of synthetic GLP-1 receptor agonists with a long period of action has made it possible not only to therapeutically influence various parts of carbohydrate metabolism disorders, but also to increase the functional reserves of the target diabetes organs, reducing the risk of developing complications of the disease. Incretin-like drugs are well tolerated, with nausea being the most common side effect. The factors limiting a wider use of the drugs include their high cost and the preferred form of a subcutaneous solution. The current research is focused on the development of long-acting, oral, dual and triple agonists, fixed-dose combinations, and small molecule drugs.Conclusion. GLP-1 receptor agonists are a class of effective and safe drugs for the treatment of diabetes and obesity, which is rapidly developing in the most advanced areas of pharmacy. A further development of this group and the solution of the identified problems will open up new opportunities for the treatment of diabetes and its complications.

Verification of the Morphofunctional Disorders Level of the Hepatorenal System during the Feline Tripelphosphate Urolithiasis

Introduction. The available information referring to the feline urolithiasis pathogenesis does not fully reflect the nature of changes taking place in the body, because it does not take into account the existing liver-kidney interrelationship. A systemic approach to studying this problem enables development of the targeted diagnostic strategies, increase of the subsequent therapeutic efficacy, as well as reduction of the possible clinical harm of polypragmasia. The aim of this article is to study the interrelationship between the nature of the hepatorenal system morphofunctional disorders and the level of metabolic processes in cats sick with struvite urolithiasis with the signs of cystolithiasis.Materials and Methods. The objects of the research were cats: the 1st experimental group consisted of the outbred female cats with tripelphosphate urolithiasis with signs of cystolithiasis, the 2nd experimental group — outbred castrated male cats with tripelphosphate urolithiasis with signs of cystolithiasis, the control group was mixed of the clinically healthy male and female animals. During the research, the results of the sick animals' clinical study, morphological and biochemical blood serum tests, hepatorenal system transabdominal ultrasonography were used, the urine macroscopic and biochemical examinations as well as urine sediment microscopy were carried out.Results. Against the background of hyperazotemia in sick animals (UREA — 14.70±1.30 mmol/L and 17.05±1.60 mmol/L; CREA — 173.90±6.06 μmol/L and 182.30±7.54 μmol/L; URIC ACID — 69.30±4.50 μmol/L and 73.48±4.83 μmol/L) and water-electrolyte metabolism disorder (Ca+2 — 2.89±0.05 mmol/L and 3.04±0.12 mmol/L; P+3 — 3.12±0.06 mmol/L and 3.20±0.09 mmol/L; iCa+2 — 1.39±0.03 mmol/L and 1.42±0.02 mmol/L; Cl- — 125.58±1.19 mmol/L and 129.90±1.06 mmol/L) there were observed: a disorder in the hepatobiliary system functioning due to elevation of the main hepatic transaminase activity (AST — 41.74±5.35 unit/L and 49.30±6.74 unit/L; ALT — 85.82±6.15 unit/L and 90.05±6.50 unit/L; ALКP — 45.61±3.10 unit/L and 48.16±2.86 unit/L; AAR — 0.49±0.03 and 0.54±0.02), elevation of total bilirubin level (BILT — 5,76±0,15 μmol/L and 6,08±0,24 μmol/L) and bilirubin direct (BILD — 1,40±0,03 μmol/L and 1,62±0,02 μmol/L), as well as elevation of the gamma-glutamyl transpeptidase (GGT — 6,67±1,01 unit/L and 7,90±0,90 unit/L) and lactate dehydrogenase (LDH — 215,47±10,30 unit/L and 219,04±9,27 unit/L) activity level. The acoustic shadowing of the hepatorenal system organs confirmed the signs of acute hepatitis against the background of cystolithiasis due to the existing anatomical relationship between kidneys and liver.Discussion and Conclusion. The results of the sick animals’ blood serum examination indicated the progression of the hematopoietic dysfunction during the tripelphosphate urolithiasis, which contributed to the development of the circulatory tissue hypoxia in the liver-kidney system. The development of the hyperazotemia contributed to the elevation of the main hepatic transaminase activity and building-up of the functional disorders in the hepato-biliary system of sick cats in response to the acute inflammatory process going on in the urogenital tract. The carbohydrate and lipid metabolism disorders indicated the liver metabolic activity disorder and its parenchymal damage on the background of urolithiasis. The electrolyte and water metabolism disorders, the development of the hyperproteinemia in test cats with the tripelphosphate urolithiasis contributed to the damage of the hepatorenal system organs due to development of the compensated metabolic acidosis and hyperchloremia.

Prevention of obesity and carbohydrate metabolism disorders in the population at an industrial facility.

One of the urgent tasks of modern healthcare is the development of measures aimed at preventing obesity in the able-bodied population, including in the Republic of Kazakhstan, which would reduce economic losses and increase the coefficient of life expectancy in the population. To identify measures for the early prevention of excess weight, obesity, and carbohydrate metabolism disorders in the able-bodied population at an industrial facility in Kazakhstan. The study involved 662 people (574 men and 88 women) aged 19 to 64 years. The subjects were divided into 2 groups: the main group - persons with obesity (242 people) and the control group - relatively healthy persons (422 people). The diagnosis of obesity was made based on the medical history of a patient, external examination, and physical, laboratory, and instrumental assessment. Three main factors influencing the development of obesity have been identified: a significant level of inactivity; serum glucose; the presence of comorbidities. Other factors (gender and age, smoking) do not have a significant effect on the increase in the body mass index of persons working at an industrial facility. Accordingly, a priority in the prevention of obesity is a healthy lifestyle, involving regular physical activity and a healthy balanced diet.

Changes in the synthesis of short-chain fatty acids under the influence of various factors in healthy people and patients with type 2 diabetes mellitus

Short-chain fatty acids (SCFAs) are an important link in the maintenance and normalization of some important body functions. Recently, the metabolic component of the SCFAs effects has also been actively studied; the effect on body weight, insulin resistance and glycemia is of particular interest in the context of the prevention and treatment of carbohydrate metabolism disorders. In this regard, it is relevant to study the characteristics of SCFAs' production in patients with impaired carbohydrate metabolism, mainly with type 2 diabetes mellitus (T2DM). The purpose of the research was to study the modern data on the synthesis peculiarities of SCFAs in healthy people and patients with impaired carbohydrate metabolism. Material and methods. The data of domestic and foreign literature presented in PubMed, Google Scholar, ResearchGate, Elsevier, eLibrary, CyberLeninka databases, published mainly over the past 10 years, have been analyzed. Results. According to the concept of the philometabolic nucleus, bacteria of certain species, which are of the greatest importance compared to the rest, are responsible for the synthesis of specific SCFAs. The gut microbiota (GM) has the property of plasticity - the ability to change its composition under the influence of various factors. Most studies describe the effect of GM and its metabolites on the carbohydrate metabolism, but an equally important aspect of this process is the effect of carbohydrate metabolism disorders on GM and its functional activity. In case of disorders of carbohydrate metabolism, some altered components of homeostasis negatively affect GM and its production of SCFAs. As a result, the total amount and variety of SCFAs decrease, which exacerbate the imbalance in relation to carbohydrate metabolism. There is evidence that in patients with T2DM, the concentration of butyrate, which has a positive effect on insulin resistance, body weight, fasting glycemia and postprandial glycemia, decreases. The concentration of propionate and acetate, which didn't show such a pronounced positive effect in studies on carbohydrate metabolism, on the contrary, increases. Conclusion. The production of SCFAs by GM representatives depends on many factors, such as nutrition, physical activity, medication intake and the presence of chronic diseases. Numerous studies have confirmed the difference in the characteristics of the production of SCFAs in patients with T2DM and healthy people. The study of the peculiarities of GM metabolism in patients with T2DM is a tool in understanding the basics of therapy and lifestyle correction in both patients with T2DM and healthy people in order to prevent disorders of carbohydrate metabolism.

Значение исследования генетических маркеров в лечении и профилактике ожирения у детей и подростков

Aim. To consider the role of hereditary predisposition in the formation of obesity, and to analyze the importance of genetic marker studies in the treatment and prevention of obesity in children and adolescents. Key points. The increasing prevalence of obesity among children and adolescents over the past decades is one of the most important medical and social problems, since obesity contributes to the emergence of such non-infectious diseases as type 2 diabetes mellitus and arterial hypertension, which are rightly considered a non-infectious epidemic of the 21st century. At the same time, the role of hereditary predisposition in the formation of obesity is well known, and therefore the search for its genetic markers becomes relevant. Conclusion. Genetic markers help not only to identify patients at risk for obesity, but also to diagnose metabolic disorders at early stages: dyslipidaemia, disorders of carbohydrate metabolism, early manifestations of endothelial dysfunction, which will help to prevent the development of heart attacks, strokes, type 2 diabetes mellitus, and thus reduce disability and mortality from non-infectious diseases. Along with this, the isolation of certain genetic markers and their combinations will allow the creation of personalized obesity treatment and prevention programs. Keywords: obesity, children, adolescents, genetic markers, gene polymorphisms.

Показатели оксидативного стресса и дисфункции эндотелия при сахарном диабете 2-го типа: риски и фокус на диетотерапию

Type 2 diabetes (T2D) is a chronic metabolic disease that poses a significant threat to public health worldwide. Carbohydrate metabolism disorders in T2D are closely related to oxidative stress. Numerous vascular complications are the main cause of disability and mortality in this disease. Objective. Comparative evaluation of the indices of oxidative stress and endothelial dysfunction with anthropometric and biochemical parameters in T2D patients. Patients and methods. The study included 55 patients with T2D and 58 patients with class 1–3 obesity without diabetes. Patients with T2D received a standard treatment with oral sugar-lowering drugs, hypolipidemic and hypotensive therapy as indicated. All patients underwent measurements of anthropometric parameters (height, weight, body mass index), indices of carbohydrate and lipid metabolism, antioxidant status and endothelial dysfunction, triglycerides-glucose index, and pulse wave velocity. Statistical processing of the results was performed using SPSS 23.0 software. Results. Several correlations were found between oxidative stress indices and clinical and metabolic parameters characterizing the state of carbohydrate and lipid metabolism and anthropometric indices in patients with T2D. The level of high-sensitivity C-reactive protein was almost twice as high in T2D patients compared to patients with obesity (11.1 ± 2.58 mg/L and 6.77 ± 1.11 mg/L, respectively). A negative correlation between the levels of superoxide dismutase and fasting blood glucose was determined (r = -0.30, p &lt; 0.005). Conclusion. The study revealed a strong correlation between oxidative stress indices, markers of endothelial dysfunction and cardiometabolic disorders in patients with T2D. The influence on oxidative stress/antioxidant defense indices may become an additional therapeutic link in the treatment of T2D patients. Key words: reactive oxygen species, endothelial dysfunction, oxidative stress, type 2 diabetes

Ассоциации полиморфизма гена параоксаназы 1 с поражением коронарного русла у больных хронической ишемической болезнью сердца и сахарным диабетом 2-го типа

Aim. To determine the features of coronary lesions in patients with chronic coronary heart disease (CHD) and type 2 diabetes mellitus (DM), to analyze their relationship with polymorphic variants of the paraoxonase gene (PON) 1. Design. A cross-sectional retrospective observational study. Materials and methods. The study included 200 patients with a stable form of IHD, divided into two groups: the main group included 112 people with IHD in combination with type 2 diabetes, the comparison group included 88 patients without carbohydrate metabolism disorders. All patients underwent selective coronary angiography (CAG) using a General Electric INNOVA 3100IQ angiographic unit (GE, USA) according to the M. Judkins method. Real-time polymerase chain reaction (PCR) was used to determine the rs622 polymorphism of the PON1 gene. Statistical processing of the obtained results was carried out using the IBM SPSS Statistics Version 25.0 software package (International Business Machines Corporation, USA). Results. In patients with coronary artery disease on the background of type 2 diabetes, coronary lesions were more often of a multivessel nature (p = 0.015) with the development of hemodynamically significant stenoses (p = 0.027); compared with patients with coronary artery disease without diabetes, they had more cases of lesions in the middle and distal parts of the arteries (p = 0.005 and p = 0.038, respectively). Multivascular coronary disease in patients was associated with the presence of the GG genotype rs622 of the PON1 gene (in the main group p = 0.010, odds ratio (OR) = 5.098, confidence interval (95% CI) — 1.337–19.433, in the comparison group p = 0, 02, OR = 7.143, 95% CI — 1.287–39.630). The AG genotype of the rs622 polymorphism of the PON1 gene has a protective effect against widespread lesions of the coronary arteries in patients with coronary artery disease and type 2 diabetes (p = 0.019, OR = 0.377, 95% CI — 0.165–0.860) and the development of hemodynamically significant stenoses of the coronary arteries in patients with IHD without diabetes (p = 0.005, OR = 0.255, 95% CI — 0.966–0.676). Conclusion. In patients with coronary heart disease and type 2 diabetes, coronary angiography demonstrated pronounced atherosclerotic changes in the coronary arteries. Multivessel coronary lesion is associated with the GG genotype of the rs622 polymorphism of the PON1 gene, which determines the possibility of predicting and further preventing the development of coronary heart. Key words: coronary heart disease, coronary atherosclerosis, type 2 diabetes mellitus, multivessel lesion, gene polymorphism, paraoxanase 1