BACKGROUND: Less than a year has passed since the start of the new coronavirus infection COVID-19 pandemic caused by SARS-CoV-2. First published research results demonstrate a frequent increase in glycemia in patients without previously diagnosed carbohydrate metabolism disorders. A possible relationship between the carbohydrate metabolism state and the course of COVID-19 is considered.

AIM: To identify the incidence of known and newly diagnosed diabetes mellitus (DM) in hospitalized patients with COVID-19 and evaluate the relationship between glycated hemoglobin (HbA_1c), inflammation markers and infectious disease severity.

METHODS: A single-center, cross-sectional, retrospective study included 155 patients with confirmed COVID-19 and bi- lateral polysegmental viral pneumonia hospitalized in the Endocrinology Research Centre, Russian Federation. Diagnosis of carbohydrate metabolism disorders was based on the HbA_1c level, blood glucose level at admission (BGA) and fasting plasma glucose (FPG). Patients were divided into 2 groups: without the previously diagnosed DM (n=129, 83.3%) and with known history of DM (n=26, 16,7%). Patients without previously diagnosed DM were divided into subgroups according to HbA_1c levels: ≤6,0% (Group A), >6,0% HbA_1c, <6.5% (Group B), ≥6,5% (Group C). Additionally, insulin, interleukin 6 (IL-6) and D-dimer levels were measured in all patients. Blood oxygen saturation (SpO₂) was measured by pulsoximetry, computerized tomography of lungs with calculation of lung parenchyma damage percentage.

RESULTS: Type 2 DM was previously established in 16.7% of all included patients. Among patients without DM history, DM was revealed in 8 patients (5.2%), based on HbA_1c, FPG and BGA. In 66 patients (42.6%) we observed no changes in carbohydrate metabolism. In 55 patients, the interpretation of carbohydrate metabolism state was difficult due to inconsistency of HbA_1c level with FPG and BGA: in particular, the level of HbA_1c ≥ 6.5% (which corresponds to the diagnostic threshold of the DM) was detected in 19 patients (12,2%) with normal FPG and BGA. No true stress hyperglycemia on admission and according to FPG was reported. Despite the presence of confirmed DM, HbA_1c levels positively correlated with inflammatory markers (erythro- cyte sedimentation rate, C-reactive protein, IL-6) and SpO₂. Patients with a HbA_1c ≥6.5% without DM history had the most severe course of the disease: longest duration of hospitalization, largest damage of the pulmonary tissue, and high lethality.

CONCLUSION: The incidence of DM among patients hospitalized with COVID-19 was 21.9% (16.7% had previous diagnosis of DM, 5.2% — newly diagnosed), which is 1.5 times higher than in general population in a comparable age category. It is difficult to assess the carbohydrate metabolism disorders in patients in acute infectious period. An increased level of HbA_1c (≥6.5%), first detected in the acute period of infection, in combination with normal FPG and BGA parameters, cannot be a diagnostic criterion and requires dynamic monitoring. HbA_1c level can be considered as a predictive factor of COVID-19 severity, independent of DM.

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.

AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met^® as compared with any other combination therapy approaches used in everyday clinical practice.

MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin >7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met^®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA_1c <7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.

RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met^® group, 68.7% of patients achieved an HbA_1c level of <7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p <0.001). Galvus Met^® therapy contributed to a significantly greater decrease in HbA_1c levels by the end of the study compared to other combinations (delta HbA_1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p <0.001). In the same group, the average level of HbA_1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p <0.001. In the Galvus Met^® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p <0.001. The frequency of hypoglycemia episodes in the Galvus Met^® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met^® group, there were significantly fewer adverse events (4.9% versus 17.7%, p <0.001).

CONCLUSIONS: In real clinical practice, Galvus Met^® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA_1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy.

BACKGROUND: Incidence of Type 2 Diabetes Mellitus (T2DM) and associated dysglycemic conditions, increasing the risk of diabetes development, continues to rise worldwide, most notably due to ever-growing obesity rate. Early identification of the persons who are exposed to the risk of T2DM development holds much significance for prevention of both this disease and associated cardiometabolic complications.

AIM: To study characteristics of insulin secretion and insulin sensitivity among obese children and adolescents versus the glycemic level 60 minutes (GL60) after the standard oral glucose tolerance test (OGTT).

METHODS: This open-label comparative cross-sectional study involved 613 children in the age between 6 and 17.9 years old with constitutive-exogenous obesity, divided into 2 groups: 173 patients with GL60 level ≥ 8.6 mmol/L and 440 children with GL60 level < 8.6 mmol/L. They underwent a screening for dyslipidemia, non-alcoholic fatty liver disease, arterial hypertension and impaired glucose tolerance (IGT). Insulin secretion was evaluated on the basis of maximal (IRI max), average level (IRI avg) of insulin in the course of OGTT and insulinogenic index (IGI), insulin resistance (IG) — by Matsuda index.

RESULTS: The groups were comparable in the terms of age, sex, sexual maturation stage and obesity level. Children with GL60 level ≥ 8.6 mmol/L were characterized by higher IR (Matsuda 2.8 ± 2.3 vs 3.5 ± 2.2, р < 0.01), hyperinsulinemia (IRI max 190.0 ± 59.5 vs 157.1 ± 63.4 μU/ml, р < 0.001, IRI avg 115.3 ± 59.7 vs 90.2 ± 54.1 μU/ml, p < 0.001) along with low IGI value (1.84 ± 1.62 vs 2.61 ± 1.3, р < 0.01), which is indicative of the first phase insulin secretion impairment. The lowest IGI values were found among the "GL60 level ≥ 8.6 mmol/L" group patients with IGT (1.4 ± 0.9). Besides, the patients with GL60 level ≥ 8.6 mmol/L are characterized by the higher rate of metabolic complications in the form of impaired glucose tolerance, arterial hypertension, fatty hepatosis and steatohepatitis.

CONCLUSIONS: GL60 level ≥ 8.6 mmol/L can be used as an additional marker for metabolically complicated obesity among children and adolescents with a high risk of the carbohydrate metabolism disorder development.

BACKGROUND: Diabetic foot ulcer (DFU) is a dangerous complication of diabetes mellitus (DM), which can lead to the development of chronic wounds and amputations. Recombinant human epidermal growth factor (rhEGF) can be used as an adjuvant treatment for chronic wounds resistant to standard treatment. Studies have demonstrated its clinical efficacy, however, there is insufficient information on the long-term results of treatment, its safety and the effect on the progression of diabetes complications, adverse cardiovascular events and the development of cancer.

AIM: To assess the long-term results of rhEGF therapy for trophic foot ulcers in individuals with multiple complications of diabetes.

METHODS: The study included 20 patients with type 1 and type 2 diabetes and various forms of DFS without critical ischemia, who had previously been treated with DFS using rhEGF in order to assess the general condition, progression of microand macrovascular complications of diabetes, adverse cardiovascular events, the development of cancer and the quality of life.

RESULTS: There was a statistically significant difference between the area of wound defects, the percentage of granulation tissue that filled the wound defect, before the start of rhEGF treatment and at the time of discharge from the hospital (p <0.05). During treatment with rhEGF, mild adverse events were observed in 35%. Complete epithelialization of wounds in most patients occurred in 3 [2; 4] months. In 11.76%, the wound was not completely epithelialized. Relapse occurred in 5.8% due to non-compliance with limb unloading. Minor amputation was performed in 1 patient. Progression of diabetic retinoand nephropathy was revealed in 23.5%. 11.76% suffered myocardial infarction of unknown age, 1 patient (5.88%) suffered acute cerebrovascular accident. Serious adverse events in the form of PE with a fatal outcome and critical ischemia of the lower limb were recorded in 5.8%.

CONCLUSIONS: As a result of the study of long-term results of rhEGF treatment of chronic foot wounds, a low percentage of relapses and small amputations, the absence of high amputations and oncological diseases, the development of serious adverse events in 2 patients, the progression of diabetic retinoand nephropathy in 4 patients, the development of IM of unknown age in 2 patients was recorded. and stroke in 1 patient after rhEGF therapy.

Concerning the uncontrolled growth in the incidence of obesity and Type 2 Diabetes Mellitus (T2DM), numerous research have been carried out to study the pathogenetic mechanisms of progress of these diseases and development of new methods for their prevention and treatment in recent years. T2DM is known to be a multifactorial disease, in the development of which both lifestyle and various environmental factors, and genetic predisposition are involved. At the same time, in recent years, a theory has been discussed that intestinal dysbiosis, which is caused with quantitative and qualitative changes in the gut microbiota (GM) is one of the mechanisms of obesity and T2DM development. At the moment, various methods have been proposed for restoring the normal composition of GM, including the administration of prebiotics and metabiotics that stimulate the growth of gut flora, as well as probiotics, which directly include the necessary beneficial bacteria (mainly Bifidobacterium and Lactobacillus). Fecal microflora transplantation (FMT), which allows transferring an entire microbial community into the recipient's body, rather than individual bacteria is the newest and least studied method of GM normalization. In this connection, this method of GM influencing is of great interest for the prevention and treatment of metabolic diseases.

Biosimilars are biological drug products that have an equivalent clinical profile with innovator biotherapeutics but are developed under a reduced program. To this end, specific comparability approaches are followed based on reverse engineering that involves a thorough analysis of the innovator biotherapeutics and the development of the version of the latter, which should be as much as possible similar with respect to structural and functional characteristics with the innovator. This approach includes the evaluation and comparison between the biosimilar and innovator biologic with respect to the molecular structure and impurity profile and of biological activity in in vitro settings as well as pharmacokinetic, pharmacodynamic, and immunogenicity characteristics on human subjects. Where considered necessary, animal studies or phase 3 clinical studies might be performed when residual uncertainties remain in terms of biosimilarity, that could not have been resolved in the previous tests and trials. Any potentially inevitable differences should be insignificant for safety and efficacy. The state-of-the-art methods of biotechnology and analytics, when applied in line with the appropriate scientific and regulatory requirements, can allow developing similar biologics where no difference in the clinical profile exists with the respective innovator product. Available experience demonstrates the lack of major problems due to the incomparability between the biosimilar and corresponding reference biologics when applicable scientific standards and regulatory recommendations are met.