Aim of the study. To study the associations of genetic variants identified by genome-wide genotyping with clinical and metabolic characteristics of patients with newly diagnosed type 2 diabetes mellitus (T2DM), including basal and postprandial glucagon-like peptide-1 (GLP-1) and glucagon levels, as well as a pancreatic β-cell function index (HOMA-B). Material and methods. Genome-wide genotyping of DNA from 100 patients with newly diagnosed T2DM was performed using Illumina Infinium I Array microarrays. Genetic association analysis was performed using generalized linear models (GLMs) within an additive genetic model, adjusted for age, sex, and the first two principal components of a principal component analysis (PCA). GLP-1 and glucagon levels were measured fasting and 30 minutes after a standard breakfast, and insulin levels were measured fasting and 120 minutes after a standard breakfast. The HOMA-B index was calculated based on glucose and insulin values. The genome-wide significance threshold was set at p <5 × 10^-8. Results. More than 30 genetic variants showed significant associations with fasting GLP-1 levels, including loci in genes involved in myocyte and adipocyte differentiation (HDAC9, rs17347800; p = 2.83 × 10^-8), angiogenesis (EFNB2, rs56077446; p = 8.73 × 10^-10), cholesterol transport and obesity (INSIG2, rs62164898; p = 1.47 × 10^-10), and the switch between glycolysis and oxidative phosphorylation (ADCY10, rs73022199; p = 7.16 × 10^-9). No statistically significant associations were found for post-stimulation GLP-1 levels. Basal glucagon concentration was associated with the loci AKAP14 (rs141362915; p = 2.22 × 10^-10), EGR2 (rs2664317; p = 1.3 × 10^-8), CNTN3 (rs676403; p = 8.15 × 10^-9), glucagon level 30 min after exercise – with the genes GPR19 (rs10772590; p = 1.81 × 10^-8), pseudogene KRT8P17 (rs3005547; p = 1.35 × 10^-9), region AL049634.2‑SIRPB1 (rs3848789; p = 2.56 × 10^-8) and SLC45A4 (rs78605132; p = 1.65 × 10^-8). HOMA-B was associated with the unannotated loci AL354984.1 (rs6015149; p = 4.33 × 10^-9) and AC034195.1 (rs7624611; p = 2.3 × 10^-9). Conclusion. Genetic variants associated with basal GLP-1 levels in patients with newly diagnosed T2DM were identified for the first time. The lack of significant associations for stimulated GLP-1 levels may indicate differences in the genetic regulation of basal and postprandial incretin secretion. Different sets of associated genes for basal and stimulated glucagon levels support the existence of discrete mechanisms of genetic control of these conditions. The obtained data expand our understanding of the genetic regulation of the incretin system and glucagon secretion in T2DM, which may be important for the development of personalized approaches to therapy. 

Aim of the study. To comprehensively assess cardiovascular risk factors in women with premature ovarian insufficiency (POI) by analyzing EAT thickness and identifying factors associated with its increase (≥5.1 mm). Materials and methods. This cross-sectional study included 109 women. Participants were divided into three groups: Group 1 (n = 48) – women with a regular menstrual cycle and follicle-stimulating hormone (FSH) and estradiol levels within reference ranges (control group); Group 2 (n = 38) – women with amenorrhea lasting 3 to 12 months and elevated FSH levels >25 IU/L (confirmed once or twice with a 4-week interval); Group 3 (n = 23) – women with amenorrhea for more than one year and elevated FSH levels >25 IU/L. Assessments included anthropometry, evaluation of lipid and carbohydrate metabolism, HOMA-IR, 24-hour blood pressure monitoring, ultrasound of the brachiocephalic arteries, and echocardiography for EAT measurement. The EAT threshold of ≥5.1 mm was determined by ROC analysis; a logistic regression model was built for risk stratification.  Results. Patients with POI, secondary amenorrhea for more than 12 months, and persistently elevated FSH had higher levels of glucose, insulin, HOMA-IR, total cholesterol (TC), and LDL, lower HDL, and a higher frequency of carbohydrate metabolism disorders. The prevalence of arterial hypertension reached 47.8% in women with secondary amenorrhea for more than 12 months and persistently elevated FSH. No atherosclerotic plaques were detected. EAT thickness increased from 4.3 mm (control) to 5.7 mm (POI) and 6.0 mm (women with secondary amenorrhea >12 months and persistently elevated FSH). EAT closely correlated with lipid parameters and inversely with estrogen levels. The frequency of EAT ≥5.1 mm was 7.4, 52.2, and 100%, respectively. Independent predictors of increased EAT were TC level and smoking; the model was statistically significant (p <0.001, pseudo-R² 67.6%). Conclusion. Women with POI, amenorrhea for more than 12 months, and persistently elevated FSH have a significantly unfavorable cardiometabolic profile and a marked increase in EAT, which reflects the degree of estrogen deficiency and can serve as an accessible risk marker. The predictive model for EAT ≥5.1 mm, based on total cholesterol level and smoking status, allows for individualized risk stratification. 

Aim of the study. To evaluate the effects of canagliflozin on glucose metabolism parameters and liver function over a 6-month treatment period in patients with type 2 diabetes mellitus (T2DM) and confirmed non-alcoholic fatty liver disease (NAFLD). Additionally, to compare the efficacy of 100 mg canagliflozin therapy with that of a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin, in this patient group. Materials and methods. The study included 69 patients aged 49–69 years with T2DM and NAFLD; patients with other chronic liver diseases were excluded. Participants were randomized into two groups: G1 received 100 mg canagliflozin (n=37), and G2 received 50 mg sitagliptin (n=32). Body mass index (BMI), levels of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), glycated hemoglobin (HbA1c), and fasting glucose were measured at baseline, and then after 3 and 6 months. Adverse events and subjective tolerability were recorded. Results. The average age was 55.9 ± 9.6 years in G1 and 54.9 ± 9.2 years in G2. Baseline levels of ALT, AST, and GGT were comparable: in G1 – ALT 84.4 ± 12.8 U/L, AST 56.4 ± 15.3 U/L, GGT 116.7 ± 11.9 U/L; in G2 – ALT 88.4 ± 10.1 U/L, AST 62.3 ± 14.3 U/L, GGT 120.3±16.1 U/L. After 3 months, G1 showed significant reductions in ALT (61.7 ± 8.3 U/L) and GGT (81.4 ± 11.5 U/L), p<0.05, which were not observed in G2. After 6 months, G1 patients experienced further significant declines in ALT (46.5 ± 7.1 U/L) and GGT (58.4±8.3 U/L), p <0.05, while in G2, only GGT levels decreased significantly. Intergroup analysis revealed a more pronounced and quicker improvement in liver enzymes in the canagliflozin group. Parameters of glucose metabolism did not differ significantly in the short term, although a positive trend was noted. Conclusion. Treatment with 100 mg canagliflozin in patients with T2DM and NAFLD promotes more rapid and significant reductions in liver enzymes compared to sitagliptin, suggesting potential hepatoprotective effects of the drug in this patient cohort. 

Aim of the study. To evaluate the structure of initial therapy for type 2 diabetes mellitus (T2DM) among patients residing in Moscow in 2025 and to analyze the use of different classes of glucose-lowering drugs (GLDs) according to age, sex, presence of diabetes complications, and comorbidities. Material and methods. A retrospective analysis was performed on data from 11,382 individuals with newly diagnosed T2DM in 2025. Clinical characteristics, treatment regimens, complications, and comorbidities – including atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and chronic heart failure (CHF) – and their association with therapy type were analyzed. Results. The mean age of patients was 62.1 ± 11.9 years, with a predominance of women (54.7%). Monotherapy with oral GLDs was used in 57.6% of patients, dual therapy in 28.3%, triple or more combination therapy in 4.3%, and insulin therapy in 7.4%. Metformin was prescribed to 83.4% of patients, dipeptidyl peptidase-4 inhibitors to 26.8%, glucagon-like peptide-1 (GLP-1) receptor agonists to 3.5%, and sodiumglucose cotransporter-2 (SGLT-2) inhibitors to 1.9%. With increasing age, the proportion of combination therapy decreased (from 32.3 to  12.7%), while monotherapy use increased (from 51.6% to 72.5%). The prevalence of ASCVD increased from 1.6% in the 18–29 age group to 19.6% in patients aged 80+, CKD from 1.6 to 30.5%, and CHF from 1.6 to 3.2%. In patients with CKD and CHF, SGLT-2 inhibitors were prescribed more frequently (2.3 and 3.6%, respectively) compared to 1.8% in patients without complications. Conclusion. In real-world clinical practice in Moscow, physicians adhere to principles of a personalized approach to initial T2DM therapy. Metformin remains the drug of choice for most patients, whereas innovative drug classes (GLP-1 receptor agonists, SGLT-2 inhibitors) are more frequently used in younger individuals. The presence of comorbidities (ASCVD, CKD, CHF) significantly increases the use of drugs with cardio-renal protective effects. 

The article discusses evidence-based data indicating the potential for additional reduction of the risk of developing heart failure (HF) and its progression in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia through the use of fenofibrate. The relevance of reducing the residual risk of heart failure–related complications in patients with T2DM is considered. Results of both clinical and experimental studies are presented, demonstrating a beneficial effect of fenofibrate, an agonist of peroxisome proliferator–activated receptor alpha (PPARα), on the risk of HF development and progression. Possible mechanisms underlying the beneficial effects of fenofibrate are discussed, which may account for its impact on the risk of HF progression in patients with T2DM. Data are provided on differences between the effects of fenofibrate and those of another representative of the fibrate class, supporting the relevance of its use in clinical practice. 

Currently, there is still a need to study and implement the most effective therapeutic approaches for patients with type 1 diabetes to reduce the risk of diabetes-related complications and improve quality of life. The development and integration of continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion have enabled the creation of more advanced systems that provide automated insulin delivery. These systems automatically adjust the insulin dose every few minutes based on CGM data, helping to achieve glycemic targets while significantly reducing the burden on the patient. This article provides an overview of the most popular automated insulin delivery systems, including open-source systems that have not yet received regulatory approval. The review emphasizes that, regardless of the type of device, clinical effectiveness largely depends on how successfully the patient masters the principles of insulin pump therapy and uses all the functions of the systems. Despite all the technological advances, the patient's active participation in managing insulin delivery currently remains essential. 

Diabetic foot syndrome (DFS) and gout are interrelated diseases that often accompany diabetes mellitus, where hyperuricemia is a key risk factor for the progression of lower limb damage and systemic disorders. This literature review analyzes the pathogenetic role of uric acid in the development of DFS, emphasizing its effect on inflammation, neuropathy, and amputation risk, while the effect of uric acid on amputations remains poorly understood in the literature. The key mechanisms of hyperuricemia influence on diabetes include excessive intake of purines from food, impaired uric acid transport, activation of proinflammatory pathways that exacerbate diabetic neuropathy and contribute to the chronization of ulcerative defects. Special attention is paid to comorbid conditions such as cardiovascular diseases and chronic kidney disease, which also worsen the outcomes of DFS and increase mortality. The therapy section presents the main modern strategies for reducing uric acid levels. This review emphasizes the need for uric acid screening in all patients with DFS to predict outcomes, personalize therapy, and reduce the risk of amputations.

Obesity is a complex chronic polyethological disease characterized by excessive accumulation of adipose tissue, which leads to adverse metabolic complications (diabetes mellitus, cardiovascular diseases, metabolic syndrome). Every year, obesity becomes epidemiological in nature, and according to various forecasts, by the middle of the 21st century, more than half of the adult population of the planet will have this disease. This trend is causing concern and requires drastic measures to be taken in the global health system. To date, a number of innovative pharmacological drugs have appeared in the arsenal of clinicians, allowing them to effectively manage body weight. The purpose of this review is to analyze the available data on the etiology, pathological processes underlying the development of obesity, and modern approaches to the diagnosis and treatment of this disease; to form a comprehensive understanding of this disease and identify the causes of widespread prevalence and treatment difficulties. 

Timely detection of thyrotoxicosis in the elderly is often difficult, since the condition in most cases is characterized by a low-symptomatic course, and the classic symptoms of hyperactivation of the sympathetic nervous system may be erased or completely absent. The presented case study describes a clinical case of a 68-year-old patient with a burdened cardiological history, in whom a paroxysm of atrial fibrillation for the first time appeared as a “cardiac mask” of thyrotoxicosis syndrome and a starting point for further diagnostic search. Despite the positive titer of antibodies to thyroid-stimulating hormone receptors, the diagnosis of diffuse toxic goiter caused complications, and therefore the patient underwent further examination to clarify the cause of thyrotoxicosis. Thyroid scintigraphy revealed a local focus of increased radiopharmaceutical uptake in the projection of a previously identified microcarcinoma. The development of severe drug-induced hepatitis while taking thiamazole made standard preoperative preparation impossible. This case highlights the diagnostic value of newly emerging atrial fibrillation in comorbid patients, the need for oncological vigilance even in relation to nodes with signs of functional activity, as well as the importance of a personalized interdisciplinary approach in complex clinical situations. 

The paper presents a clinical case of a patient with newly diagnosed type 2 diabetes mellitus (T2 DM), in whom severe decompensation of carbohydrate metabolism probably contributed to the worsening of chronic heart failure with a reduced ejection fraction against the background of chronic kidney disease of mixed genesis. Special attention is paid to the strategy of choosing cardio- and renoprotective therapy using drugs from the group of sodium-glucose cotransporter type 2 inhibitors, angiotensin converting enzyme inhibitors and highly selective antagonists of mineralocorticoid receptors in order to timely multifactorial therapeutic effects on various components of cardioreno-metabolic syndrome in a multimorbid patient. In the presented clinical case, a long-term asymptomatic course of T2DM2 (glycated hemoglobin level – 17.5%), against the background of cardio-reno-metabolic syndrome, could serve as a trigger in the development of rhythm disturbances that required electro-pulse therapy. The clinical case demonstrates the need for active screening of carbohydrate metabolism in patients at high and very high risk of cardiovascular complications, as well as the importance of an interdisciplinary approach in the management of such patients.