Background. Type 1 diabetes mellitus (T1DM) is characterized by pronounced genetic heterogeneity, with genes of the HLA complex playing a key role in disease susceptibility. The distribution and contribution of HLA alleles and haplotypes vary substantially between populations, highlighting the need to study population-specific features of genetic predisposition in different cohorts.

   The aim: to investigate the spectrum and frequency of HLA genes and haplotypes associated with the risk of T1DM in the Volga region.

   Material and methods. A multicenter comparative study included 507 children: 310 patients with newly diagnosed T1DM and 197 healthy siblings from three regions of the Volga area. HLA typing of loci HLA-A, -B, -C, -DR, -DQ, and -DP was performed using allele-specific PCR followed by sequencing.

   Results. Patients with T1DM demonstrated significant differences in the distribution of HLA class II haplotypes compared with healthy siblings. The DR3–DQ2 and DR4–DQ8 haplotypes were significantly associated with increased disease risk, whereas DRB1*15:01–DQA1*01:02–DQB1*06:02 and DRB1*07:01–DQA1*02:01–DQB1*03:03 showed a strong protective effect. For the DPB1 locus, opposite associations were observed: DPB1*01:01 was associated with increased T1DM risk, while DPB1*04:02 was associated with reduced risk. Interaction analysis indicated a predominantly additive effect of DPB1 and DR–DQ haplotypes, without evidence of epistatic interactions. Among HLA class I loci, B*08:01 and B*39:01 were associated with increased T1DM risk, whereas B*57:01 demonstrated a protective effect. Interactions between HLA class I and class II loci were generally additive, and some associations were partially explained by linkage disequilibrium within the HLA
region.

   Conclusion. The leading role of HLA class II haplotypes (DR3–DQ2 and DR4–DQ8) in genetic susceptibility to type 1 diabetes was confirmed. The haplotypes DRB1*15:01–DQA1*01:02–DQB1*06:02 and DRB1*07:01–DQA1*02:01–DQB1*03:03 were associated with reduced disease risk. HLA class I loci and DPB1 provide an additional, predominantly additive contribution to T1DM risk, with DPB1*01:01 conferring increased risk and DPB1*04:02 and B*57:01 showing protective effects.

   Introduction. Gut microbiota (GM) metabolism in patients with type 2 diabetes mellitus (T2DM) has a number of features, including changes in the functional characteristics of microorganisms and, as a result, changes in the levels of the main metabolites of GM – short-chain fatty acids (SCFA).

   The purpose of the study. To investigate the features of the SCFA in patients with T2DM receiving innovative hypoglycemic therapy combined with metformin.

  Materials and methods. The study included 80 patients with T2DM aged 45–60 years, with the duration of the disease to 5 years, HbA1c did not exceed 7.5 %, BMI was 27–35 kg/m². All patients received metformin and SGLT-2 inhibitors or metformin and DPP-4 inhibitors.

   Results. The median age of the patients was 55 [52-57] years, and the median duration of T2DM was 2 [1-4] years. The average BMI in the group was 31.22 ± 2.42 (95 % CI: 30.68–31.76) kg/m². The average HbA1c level – 6.16 ± 0.79 (95 % CI: 5.98–6.33) %. A significant decrease in the level of the amount of SCFA (3,664 [2,053–7,014] mg/g) was revealed compared with the people without T2DM (10.5 ± 1.5 mg/g). The absolute concentrations of acetic, propionic, and butyric acids are also almost threefold reduced (1.93 [0.95–3.99] mg/g, 0.82 [0.39–1.58] mg/g, 0.55 [0.30–1.31] mg/g). The anaerobic index was shifted towards sharply negative values and amounted to -0.76 ± 0.25 (95 % CI: from -0.81 to -0.70). There were no statistically significant differences between the treatment groups of patients.

   Conclusions. The data obtained highlight the unresolved problem of decompensation of the microbiotic link in the pathogenesis of T2DM.

   Relevance. Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer. The increasing incidence of thyroid cancer coincides with the growing prevalence of obesity and metabolic disorders; however, their impact on the risk of recurrence remains in-sufficiently studied.

   Objective. To evaluate the role of obesity and associated metabolic disorders in determining the risk of PTC recurrence.

   Materials and Methods. The study included 145 patients with verified prostate cancer who underwent surgery until 2023. A retrospective analysis of clinical, anthropometric, and metabolic parameters was performed. The patients were divided into 2 groups: Group 1 – the patients with absence of recurrence of the disease for 5 years or more, Group 2 – the patients with a recurrence of prostate cancer. Body mass index (BMI), waist circumference (WC), duration of obesity, indicators of carbohydrate and lipid metabolism, and the HOMA-IR index were evaluated. ROC analysis and logistic regression were performed.

   Results. Disease recurrence was observed in 16 (11 %) patients, on average 8.9 (4.3–11.2) years after the primary surgical intervention. Patients with recurrence had higher values of BMI (32.23 vs. 26.88 kg/m²; p < 0.001), WC (99.03 vs. 86.02 cm; p< 0.001), HOMA-IR (5.57 vs. 3.25; p < 0.001), and a longer history of obesity (19.02 vs. 10 years; p < 0.001). Threshold values associated with an increased risk of recurrence were: BMI ≥ 28.13 kg/m², obesity duration ≥ 12 years, HOMA-IR ≥ 3.90, WC ≥ 90 cm. Logistic regression showed an independent contribution of all metabolic factors to the risk of recurrence.

   Conclusion. Obesity, its duration, and the severity of metabolic disorders, primarily insulin resistance, are significant predictors of PTC recurrence. The identified threshold values can be used for risk stratification and optimization of patient follow-up. Moreover, all patients had abdominal obesity before and after surgery, suggesting that persistent obesity acts not only as a risk factor for development but also as a powerful driver sustaining the risk of recurrence for many years after treatment.

   Euglycemic diabetic ketoacidosis (EDKA) is a distinct form of diabetic ketoacidosis characterized by severe metabolic acidosis in the presence of normal blood glucose levels. The increasing incidence of EDKA is associated with the widespread use of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. This review summarizes current data on the pathogenesis, risk factors, diagnostic criteria, and therapeutic approaches to EDKA. Emphasis is placed on the importance of early recognition and timely correction of water–electrolyte imbalance to prevent complications.

   Special attention is given to the clinical features of EDKA in patients receiving SGLT2 inhibitors and to strategies for preventing recurrence.

   Systematization of existing knowledge may improve clinicians’ awareness and optimize the management of patients with this potentially life-threatening complication of diabetes mellitus.

   Objective: to present modern approaches to diagnosing presymptomatic stages of type 1 diabetes mellitus (T1DM) using islet autoantibody screening.

   T1DM is a chronic autoimmune disease characterized by progressive destruction of pancreatic β-cells, with a steadily increasing global prevalence. The current concept defines three stages of the disease: Stage 1 is characterized by the presence of ≥2 autoantibodies with normoglycemia; Stage 2 involves ≥2 autoantibodies with dysglycemia; Stage 3 represents clinical manifestation with hyperglycemia. Traditional diagnosis at the onset of clinical symptoms leads to a high rate of presentation with diabetic ketoacidosis (up to 90 % of cases), which is associated with unfavorable long-term outcomes. Therefore, early diagnosis of T1DM at presymptomatic stages appears highly relevant. Screening programs involving first-degree relatives of T1DM patients and individuals with other autoimmune diseases have demonstrated a 90% reduction in diabetic ketoacidosis at disease onset, which may contribute to preserving residual β-cell function and improving long-term glycemic control. Implementation of early diagnostic and monitoring programs of individuals at presymptomatic stages of T1DM are key directions for changing the disease trajectory and improving patient prognosis.

   Type 2 diabetes mellitus (T2DM) is one of the most common noncommunicable diseases of our time, reaching global pandemic proportions. Despite significant advances in understanding the pathogenesis of the disease and the emergence of new classes of hypoglycemic medications, the effectiveness of T2DM prevention and treatment remains limited, resulting in high rates of disability and mortality due to micro- and macrovascular complications.

   A key challenge hindering the development of optimal therapeutic strategies is the marked heterogeneity of T2DM.

   The disease is not a single nosological entity, but rather a syndrome encompassing a multitude of different pathological conditions characterized by chronic hyperglycemia but differing in etiology, pathophysiological mechanisms, clinical presentation, rate of progression, and spectrum of complications. In recent years, methods for stratifying T2DM based on cluster analysis of clinical and genetic data have been actively developed. A fundamental study by Ahlqvist E. et al. identified five T2DM subtypes that differ in pathogenesis, progression, and risk of complications. Concurrently, the development of genome-wide association studies (GWAS) and machine learning methods (Bayesian nonnegative matrix factorization, soft clustering) has enabled the grouping of hundreds of genetic loci into physiological clusters corresponding to β-cell dysfunction, obesity, lipodystrophy, and lipid metabolism disorders. Stable associations have been established between the identified subtypes and outcomes, including the risk of retinopathy, nephropathy, and cardiovascular events. The integration of phenotypic and genetic clustering opens up prospects for the development of pathogenetically based therapeutic strategies: early insulin administration in insulin-deficient clusters, prioritization of SGLT2 inhibitors and GLP-1 receptor agonists in the insulin-resistant cluster, a focus on weight loss in obesity clusters, and minimization of the risk of hypoglycemia in age-related diabetes.

   Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of lipids in hepatocytes caused by metabolic disorders. This disease is widespread all over the world, and its scale is only now beginning to be assessed. Due to the epidemic of associated diseases such as obesity and type 2 diabetes mellitus (T2DM2), the issues of the pathogenesis and treatment of NAFLD are becoming increasingly relevant. The main pathophysiological mechanisms of NAFLD are insulin resistance, glucotoxicity and lipotoxicity, and impaired insulin metabolism, which explains the relationship between NAFLD and T2DM. At the moment, new approaches to the drug correction of NAFLD are being actively sought. Sodium glucose cotransporter type 2 (SGLT2) inhibitors are a modern class of drugs that are used to treat T2DM2 and a wide range of related complications, such as chronic kidney disease or heart failure. The mechanism of action of SGLT2 inhibitors is based on a decrease in glucose reabsorption by the kidneys and an increase in glucose excretion in the urine by suppressing two glucose transporters in the kidneys: sodium-glucose cotransporter types 1 and 2 (SGLT1 and SGLT2). The use of this group of drugs has already gone beyond endocrine pathology, due to their proven cardio- and nephroprotective properties. Due to the improvement of the metabolic profile when using them, the question of using SGLT2 inhibitors as an independent therapy for NAFLD is being actively discussed.

   Polycystic ovary syndrome (PCOS) is considered a complex multisystem condition with a pronounced cardiometabolic profile in modern medicine. Traditional therapeutic strategies based on combined oral contraceptives and metformin are often insufficiently effective for long-term correction of metabolic risks and prevention of cardiovascular complications. This article discusses the paradigm shift in PCOS treatment, favoring the use of incretin agents – GLP-1 receptor agonists (semaglutide) and dual GLP-1/GIP agonists (tirzepatide). The multifaceted mechanism of action of these agents is analyzed, including not only weight loss and insulin resistance but also a direct impact on the pathophysiological components of the disease: hyperandrogenism, systemic inflammation, and ovarian dysfunction. The paper presents data from recent meta-analyses confirming significant improvements in anthropometric parameters and lipid profiles in PCOS under the influence of incretins. Integrating incretin therapy into PCOS management algorithms opens new possibilities for comprehensive metabolic and reproductive rehabilitation of patients, providing a personalized approach to the treatment of this heterogeneous disease.

   Diabetic foot syndrome (DFS) is one of the most severe and disabling complications of diabetes mellitus (DM), representing a clinical manifestation of systemic involvement rather than merely a localized foot defect. This literature review highlights global and Russian epidemiology of DFS, emphasizing its central role in the prevalence of non-traumatic amputations and mortality. The key pathogenetic links of DFS include diabetic peripheral neuropathy, chronic hyperglycemia, immune dysfunction, and local biomechanical factors that contribute to the formation of chronic non-healing ulcers. The review also describes the roles of diabetic neuro-osteoarthropathy, musculoskeletal foot alterations, and elevated plantar pressure, alongside skin barrier impairment and disrupted wound healing phases, which account for high rates of infection and amputation.

   Special attention is paid to the impact of comorbidities on the clinical course of DFS; these conditions aggravate the syndrome through mechanisms of systemic inflammation and a prothrombotic state, thereby increasing the risk of major adverse limb events (MALE) and overall mortality.

   Furthermore, genetic and epigenetic factors determining individual predisposition to DFS and variability in ulcer healing are discussed. The therapeutic section presents modern approaches to DFS risk stratification and management principles for diabetic foot ulcers, including the necessity of glucose-lowering therapy and timely revascularization in cases of critical limb ischemia.

   The review emphasizes the need for a multidisciplinary approach and regular foot screening in patients with significant comorbidity to reduce amputation rates and improve quality of life.

   This article presents a complex clinical case of a 26-year-old female patient with autoimmune polyglandular syndrome type 2, comprising type 1 diabetes mellitus, primary adrenal insufficiency, and autoimmune thyroiditis with severe decompensated hypothyroidism (thyroid stimulating hormone 491.84 mU/L) despite treatment with high doses of levothyroxine sodium (L-T4) – 350 mcg/day.

    The key diagnostic challenge was to differentiate true L-T4 malabsorption from pseudomalabsorption caused by polypharmacy, non-adherence to the medication regimen, and psychosomatic disorders.

   To verify the cause, an L-T4 absorption test was performed using a 600 mcg dose of L-T4, with monitoring of free thyroxine (fT4) levels. The test results demonstrated an adequate increase in fT4 of more than 240% over 6 hours, which allowed for the exclusion of true malabsorption. Based on these findings, a comprehensive therapy correction was implemented: the sequence of drug administration was optimized (L-T4 to be taken strictly on an empty stomach with a subsequent interval before taking other medications), the glucocorticoid dose was reduced, insulin therapy was adjusted, and psychotherapeutic support was prescribed. This case highlights the critical importance of objectively assessing L-T4 absorption in patients with polyendocrinopathies to select the optimal pathway for achieving hypothyroidism compensation and to develop a personalized management plan.

   The article presents a clinical case of a 55-year-old woman who was diagnosed with hyperplasia of the medial pedicle of the left adrenal gland and the formation of the left ovary against the background of pronounced manifestations of hyperandrogenism syndrome: androgen-dependent alopecia, hirsutism, arterial hypertension, fasting and postprandial hyperglycemia. Hyperandrogenism was confirmed by laboratory tests, the hormonal activity of the left adrenal hyperplasia was excluded. Using gas chromatography-mass spectrometry of daily urine and selective blood sampling from the ovarian veins with an assessment of the concentration of androstenedione and testosterone, the ovarian origin of hyperandrogenism syndrome was proved. The patient underwent laparoscopic extirpation of the uterus and appendages, followed by regression of symptoms. The normalization of hormones was biochemically confirmed after 3 months. The clinical case demonstrates the high sensitivity and specificity of gas chromatography-mass spectrometry, highlighting the importance of this method for the differential diagnosis of adrenal and gonadal diseases.