An interview with Natalia Georgievna Mokrysheva, an associate member of the Russian Academy of Science, Director of the National Medical Research Centre for Endocrinology.

 Natalia Georgievna told us how her family had impacted her choice of profession and how I.I. Dedov, an academician of the Russian Academy of Science, helped her become a doctor and a scientist. Also, she provided some piece of advice for young scientists to listen to themselves when choosing their major and unlocked the secret of how to manage to do everything.

The interview details the developments conducted by the National Medical Research Centre for Endocrinology: technologies for cell cultivation for patients and attempts to create 3D live models of tumours for studies of various drugs. The technology for cell programming and genome editing in endocrine oncology has been put in practice. The Centre has a fundamental experimental endocrinological scientific framework.

Professor Mokrysheva focused her attention on one of the most essential issues — cardiometabolic complications in patients with type 2 diabetes mellitus. Last year, the Centre for Metabolic Disorders and Obesity in Children and Adults was opened, making it possible to treat the problem of obesity in its entirety.

Aim: To review the current scales for the evaluation of a cardiovascular risk in young men (under 45 years of age).

Key Points. The common cardiovascular risk evaluation scales are used mostly for subjects of over 40 years of age, thus complicating the prognosis of cardiovascular disorders in young people and, therefore, can result in low efficiency of preventive measures in this age group. The article describes cardiovascular risk calculators that can be used for young people, and their properties, advantages and possible use in clinical practice.

Conclusion. The most useful for practical settings are QRISK3 and Mayo Clinic Heart Disease Calculator. Their use is limited since these calculators are in English. Validation of these scales in Russian young people is essential. 

Aim: To study the features of adiponectin, leptin, resistin, adipsin, interleukin 6, and tumor necrosis factor α levels in individuals with a metabolically healthy and unhealthy phenotype at different values of body weight according to the literature.

Key points. The results of foreign and domestic studies of the levels of adipocytokines in metabolically healthy and unhealthy phenotypes in individuals with different body weights are presented. Adipokines such as adiponectin, leptin, resistin, adipsin, interleukin 6, and tumor necrosis factor α were analyzed. Data are given on the pathogenetic and clinical features of the production of these biologically active substances and their effect on metabolism.

Conclusion. According to the literature, high levels of leptin, resistin, tumor necrosis factor α, interleukin 6 are associated with a metabolically unhealthy phenotype, and adiponectin, adipsin are associated with a metabolically healthy phenotype. 

Aim: To study peculiarities of various types of diabetes mellitus (DM) in young patients.

Key points. In patients with DM onset in young age, it is challenging to correctly identify the DM type, therefore, it is essential to know the peculiarities of the onset and progression of each type. DM1 patients present with severe pancreatic β-cell dysfunction. Slow immunemediated DM is diagnosed in the presence of glutamic acid decarboxylase antibodies, but without any need to use insulin for 1 year after the diagnosis. DM2 is characterised with normal or elevated C-peptide levels, absence of antibodies, and presence of some signs of metabolic syndrome. In young patients, DM with autosomal dominant inheritance can be verified, which is caused by pathogenic mutations in associated genes — MODY (Maturity Onset Diabetes of the Young).

Conclusion. A review of literature demonstrates the need in thorough differential diagnosis of a DM type if young patients present with hyperglycaemia.

Aim: To study the features of pathogenesis, diagnosis and management of patients with diabetes, frolicking during various pathologies of the exocrine part of the pancreas.

Key points. Diabetes of the exocrine pancreas (DEP) is a common problem among patients with chronic pancreatitis, pancreatic cancer, hemochromatosis, after pancreatectomy. We discuss various aspects of this type of diabetes: its etiology, pathogenesis, diagnostic features, the importance of diagnosis for proper management. There are a comparative analysis of disorders of the relationship of various pancreatic hormones in DEP, their influence on the pathogenesis of the disease and clinical significance in the differential diagnosis of DEP with diabetes mellitus 1 and 2 types.

Conclusion. The increasing incidence of chronic and acute pancreatitis, better survival rates in patients with pancreatic cancer with the subsequent development of DEP, led to the evidence that the differential diagnosis of this disease, the development of guidelines for the management of such patients have become relevant. 

Aim: to establish the features of eating disorders in patients with type 2 diabetes mellitus.

 Material and methods. Examination of 536 women with complicated T2DM aged 50–80 years was carried out on the basis of the endocrinology department of the State Budgetary Healthcare Institution “PKKB”, Perm. The DEBQ questionnaire was used to identify eating disorders.

Results. Emotional type of eating behavior was observed in 2.4% of DM2 patients, external — in 13%, restrictive — in 21%. All three eating disorders were present in 7.1% of patients, emotiogenic in combination with external — in 14.3%, restrictive in combination with emotiogenic — in 6.2%, restrictive in combination with external — in 14.6%. The emotiogenic type of eating behavior correlated with age (r = –0.598; p = 0.006), duration of diabetes (r = –0.536; p = 0.0148), body mass index (r = 0.363; p = 0.008), waist size (r = 0.384; p = 0.0361), total cholesterol (r = 0.741; p = 0.0079). A connection has been established between xternal type of eating behavior and body mass index (r = 0.567; p = 0.009), high-density lipoprotein cholesterol (r = –0.7; p = 0.0014), glycated hemoglobin level (r = 0.780; p = 0.022), triglycerides (r = 0.348; p = 0.0164). The dependence of the restrictive type of eating behavior on age (r = 0.879; p = 0.048), body mass index (r = 0.321; p = 0.021), glycemia level (r = –0.6; p = 0.01) and lipoprotein cholesterol was revealed. low density (r = –0.663; p = 0.013).

Conclusion. Established eating disorders have shown an impact on metabolic control in women with type 2 diabetes. Their detection and prevention should be considered as a priority in the dispensary observation of this category of patients. 

Aim: To determine the effects of dapagliflozin in impaired carbohydrate and fat metabolism in type 2 diabetes mellitus (T2DM).

Design: An open cohort controlled prospective study.

Materials and methods. In this study 60 patients with T2DM and obesity were examined. Dapagliflozin 10 mg was added to metformin monotherapy. Carbohydrate metabolism and fat metabolism markers were evaluated for 6 months: anthropometry, body composition analysis, assessment of adipokines (adiponectin, leptin, irisin, interleukin (IL) 6) and lipid panel.

Results. Dapagliflozin addition resulted in glycated hemoglobin level decrease by an average of 0.6% (p = 0.093) along with significant positive effects on fat metabolism markers. The mean body mass decrease was 3.3 kg (p < 0.05). There was also a significant decrease in fat mass of 3 kg (p = 0.001) and a muscle mass extension, according to a body composition analysis report, which correlated with leptin levels decrease (p = 0.073) and adiponectin and irisin levels increase (p < 0.05). A significant decrease in total cholesterol, triglycerides and low-density lipoproteins levels also occurred (p = 0.001).

Conclusion. Leptin and IL-6 levels decrease and irisin and adiponectin levels increase correlating with a fat mass reduction and muscle mass expansion occurred with dapagliflozin added to the therapy. These findings suggest the possibility of metabolically unhealthy obesity transitioning to metabolically healthy obesity. Adipose tissue dysfunction treatment as a focus of therapy may provide not only a better control of T2DM, but also cardiometabolic risks reduction

Aim: to study metabolic effects of empaglilozin in patients with type 2 diabetes and obesity.

Design. Single center prospective randomized study.

Materials and Methods. The study included 46 patients (10 men and 36 women) aged 37–69 years with previously diagnosed T2D and obesity. Patients were randomized into two groups by random numbers: in the main group (n = 22), empagliflozin 25 mg/day was added to metformin 2000 mg/day, the control group (n = 24) continued therapy with metformin 2000 mg/day. We looked such indicators, as anthropometric data were assessed: body weight (BW), waist circumference (WC), body mass index (BMI), glycemic control, and metabolic health markers (adiponectin, leptin) at baseline and after 6 months of therapy.

Results. Although we didn’t find pronounced glycemic effect in the combined treatment group, but we showed positive dynamics of anthropometric parameters — a decrease in BW (p = 0.035), WC (p = 0.04), BMI (p = 0.005) — we found a decrease in leptin levels from 28.8 ± 11.0 to 21.0 ± 9.13 ng/ml (p = 0.035). In the main group, the level of adiponectin increased statistically significantly (p = 0.002) from 9.70 ± 2.15 to 13.0 ± 3.18 μg/ml.

Conclusion. Significant non-glycemic effects of empagliflozin were obtained. 

Aim: Comprehensive (clinical, laboratory, instrumental) assessment of the clinical efficacy of metabolic disorders correction in patients with type 2 diabetes mellitus using a type 2 sodium-glucose cotransporter inhibitor.

Design: Randomized comparative study.

Materials and methods. A 26-week study included 130 patients with the presence of visceral obesity (56.3 ± 2.1 years) who did not reach the target parameters of glycated hemoglobin (HbA1c) on metformin monotherapy 2 g/day. The main group (68 people) received canagliflozin 300 mg/day, in combination with metformin 2 g/day; the control group (62 people) continued to receive monotherapy with metformin 2 g/day. At baseline and in 6 months, all patients underwent laboratory and instrumental examination methods, which included an assessment of carbohydrate metabolism (fasting glycemia (FG), postprandial glycemia (PPG), HbA1c); lipid profile (cholesterol levels, high and low density lipoproteins, triglycerides); content of adipocytokines- adiponectin (ADN), leptin (L). Visceral fat area (AVF) was assessed using a bioimpedance analyzer and magnetic resonance imaging (MRI) at the L4 level.

Results. In 6 months, both groups showed significant positive dynamics of FG, PPG and HbA1c. In main group, HbA1c decreased by 2.7 ± 0.3% (p < 0.01), in control group by 0.2 ± 0.1% (p < 0.01). The FG and PPG levels in main group decreased by 4.5 ± 0.4 mmol/L (p < 0.01 ) and 5.8 ± 0.5 mmol/L (p < 0.01), respectively, in control group by 1.3 ± 0.2 mmol/L (p < 0.01) and 1.7 ± 0.4 mmol/L (p < 0.01). The level ADN in main group increased by 102.8 ± 4.8 mcg/ml (p < 0.01), in control group by 8.2 ± 2.1 mcg/ml (p < 0.01). L in main group decreased by 10.3 ± 0.9 ng/ml (p < 0.01), in control group by 4.1 ± 0.7 ng/ml (p < 0.01). In main group, there was a decrease in the VFA of by 18.6 ± 2.3 cm2 (p < 0.01) according to MRI, in control group by 4.7 ± 2.4 cm2 (p < 0.01). According to bioimpedance analysis, there was a decrease in the area of AVF by 26.7 ± 3.2 cm2 (p < 0.01) in the main group, and by 4.7 ± 2.5 cm2 (p < 0.01) in the control group.

Conclusion. Combination therapy with canagliflozin and metformin makes it possible to achieve high clinical efficacy of carbohydrate metabolism correction in combination with a decrease in visceral fat depot and normalization levels of the main markers of metabolic health. 

Aim: To demonstrate a clinical case of a patient with diabetes mellitus secondary to chronic pancreatitis, who needs not only compensation for carbohydrate metabolism, but also correction of exocrine pancreatic insufficiency.

Key points. The patient noted a significant improvement in well-being against the background of adequate hypoglycemic therapy (nighttime metformin, sodium-glucose co-transporter type 2 inhibitors and glucagon-like peptide-1 receptor agonist, basal insulin glargine) and enzyme-replacement therapy with pancreatin minimicrospheres at a dose of 50,000 IU on main meals and up to 25,000 ED at snacks. When evaluating the glycemic profile of continuous glucose monitoring showed stabilization of blood glucose at the target range. According to the results of laboratory tests, the patient showed not only normalization of carbohydrate metabolism, but also an initially reduced level of total protein, vitamins and minerals.

Conclusion. Administration of drugs used to treat patients with type 2 diabetes mellitus for the management of patients with diabetes secondary to chronic pancreatitis is justified. At the same time, the addition of insulin is often necessary. For this group of patients, the enzyme replacement therapy of exocrine pancreatic insufficiency is as important for the correction of metabolic disorders as the usual hypoglycemic therapy. 

Aim: to present the likely pathophysiological mechanisms of hyperprolactinemia development in patients with a new coronavirus infection, as well as to present the results of clinical studies available at the time of writing the review to assess the contribution of hyperprolactinemia to the severity of the coronavirus infection.

Key points: hyperprolactinemia is considered as a negative factor contributing to a more severe course of coronavirus infection in different groups of patients. The more severe course of a covid infection is based on the development of inflammatory processes that increase with an increased level of prolactin in the blood.

Conclusion. The authors of most research papers report that experimental, clinical trials and clinical studies are needed to confirm the inflammatory and/or anti-inflammatory role of prolactin in the setting of coronavirus infection. 

Aim: To study the levels of regulatory T lymphocytes (Treg) and B-cells in peripheral blood in patients with Graves' disease in dynamics after thyroidectomy.

Design: Single center, observational, prospective, cohort, open, controlled study.

Materials and methods. The study included 96 patients with Graves' disease, mean age 42.86 ± 10.81 years. Clinical, hormonal and immunological examinations were performed against the background of persistent drug-induced euthyroidism, before surgery, and also 1, 3, and 6 months after thyroidectomy. The levels of Treg and B-cells in the blood was examined by flow cytometry using direct immunofluorescence and monoclonal antibodies. The level of antibodies to thyroid-stimulating hormone receptors (rTSH) was assessed by enzyme immunoassay. The control group consisted of 85 healthy women of the same age.

Results. In patients with Graves' disease in the dynamics of the postoperative period, there was a consistent statistically significant decrease in the titer of antibodies to rTSH: from 14.69 (8.67–19.81) to 0.81 (0.59–0.93) IU/l. The absolute amount of Treg in their blood was reduced relative to the control values already in the preoperative period and decreased even more at 6 months after thyroidectomy. The proportion of CD19+ CD5+ - and CD19+ CD5– -cells in the examined patients before surgery was significantly higher than in the control group. The content of CD19+ CD5+ cells decreased as early as 1 month after thyroidectomy and remained at the level of control values. The сontent of CD19+ CD27– -cells in patients with Graves' disease in the preoperative period was higher than in the control group, decreased to the control values 1 month after thyroidectomy and remained in this range until the end of the follow-up. The content of CD19+ CD27+ cells in patients before thyroidectomy was lower compare to control, in the period of 1–3 months it corresponded to the control values, but decreased again on the 6th month after surgery.

Conclusion. The reduction of Treg and B-memory cells in the peripheral blood in patients with Graves' disease six months after thyroidectomy remains of immunosuppressive regulatory mechanisms with an increase in the migration activity of immune cells for a long time. 

Aim: To demonstrate clinical cases of hypothyroidism in adolescents manifested under the guises of rheumatic diseases.

Key points. We presented the cases of hypothyroidism which required differential diagnostics with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). Thyroid arthropathy course is demonstrated.

Conclusion. Hypothyroidism is characterized by nonspecific symptoms (weakness, oedema) which are also typical for SLE and JIA; thyroid hormones measurement for diagnostics is necessary. If joint syndrome remains in spite of hypothyroidism compensation repeated differential diagnostics of thyroid arthropathy and JIA is required.