An interview with Elena Nikolaevna Grineva, an associate member of the Russian Academy of Science, Dr. Med. Sci.; Director of the Institute of Endocrinology at V.A. Almazov National Medical Research Centre.

Elena Nikolaevna told us that she had dreamt of becoming a doctor since her childhood; and after graduation, she joined the research centre, which is now named after V.A. Almazov. She participated in creation of a new endocrinology service, so that not only patients with diabetes mellitus and thyroid gland disorders, but also a large group of patients with pituitary gland disorders, including hormonally active masses, adrenal diseases, neuroendocrine tumours, could be followed up by an endocrinologist.

During the interview, Professor described in detail the main studies, conducted by the six laboratories of the Institute of Endocrinology. Also, she explained how functional imaging helps in diagnosing neuroendocrine tumours and how theranostics was developing. The future of neuroendocrinology is peptide receptor radiotherapy. Special attention was paid to the possible use of cell technologies for the therapy of diabetes mellitus.

The interview is concluded with a story about the study of long-term endocrine effects of COVID-19. Many endocrine organs (pancreas and thyroid gland, pituitary gland, testicles, ovaries, suprarenal glands) express ACE2, via which coronavirus penetrates the cell. It can result in their direct or immunemediated damage.

Aim. To describe the main aspects of the double diabetes concept, the challenges of diagnosing and treating this condition, as well as potential solutions to these challenges.

Key points. Our contemporary cohort of patients with type 1 diabetes mellitus shows a concerning increase in the prevalence of obesity, metabolic syndrome, and insulin resistance — characteristics that are traditionally associated with type 2 diabetes. This combination of factors has been termed double diabetes. These patients demonstrate poorer glycemic control and have an increased risk of microvascular and macrovascular complications, as well as mortality. The diagnosis of double diabetes poses a significant challenge due to the lack of well-defined diagnostic criteria. However, the estimated glucose disposal rate has emerged as a promising and reliable indicator, demonstrating a correlation with cardiovascular complications and mortality in these patients. A pressing issue revolves around the possibility of incorporating additional glucose-lowering medications in conjunction with insulin therapy for these individuals. Current researches provide controversial results.

Conclusion. The concept of double diabetes highlights the contemporary challenges facing type1 diabetic patients and endocrinologists while also revealing new opportunities for future research aimed at improving outcomes for these individuals.

Aim. To summarize the currently available information about the mechanism of development of chronic heart failure against the background of subclinical hypothyroidism.

Key points. The review article is devoted to the influence of subclinical hypothyroidism on the course of cardiovascular pathologies, in particular chronic heart failure. The mechanisms of molecular cellular disorders in this disease are presented. A special role is assigned to the protein of the myocardium phospholamban. The importance of subclinical hypothyroidism as a risk factor and as an independent nosology within the framework of comorbid conditions associated with pathology of the vascular bed is described. The pathogenesis of left ventricular dysfunction in a patient and, as a consequence, chronic heart failure in patients with subclinical hypothyroidism is shown. Data from studies of patients with cardiovascular diseases against the background of elevated thyroid stimulating hormones levels are presented. The topic of the relationship between heart rhythm disturbances and thyroid hormone deficiency is also touched upon.

Conclusion. The role of subclinical hypothyroidism in the pathogenesis of chronic heart failure has been established, not only as a risk factor for its development, but also as an independent nosological form, the presence of which naturally leads to adverse cardiovascular events.

Aim. The purpose of the review is to summarize the results of studies on the relationship between the level of omentin-1 and coronary artery disease (CAD).

Key points. Adipose tissue is currently considered as an endocrine organ synthesizing biologically active factors known as adipocytokines, which may be involved in the pathogenesis of obesity-related metabolic and cardiovascular diseases, in particular, CAD. Omentin-1 is an adipocytokine that is predominantly secreted by visceral adipose tissue and plays an important role in the development of chronic inflammatory diseases, including CAD. Two isoforms of omentin are known: omentin-1 and omentin-2. Omentin-1 is the main circulating form of omentin. Its blood level in healthy people, according to different authors, varies from 1.61 to 815.3 ng/ml. A number of studies have found that the concentration of omentin-1 in the blood of women is higher than that of men, which may be due to sexual dimorphism of adipose tissue. The results of the studies indicate that the levels of omentin-1 circulating in the blood are associated with various metabolic risk factors. The review describes the main molecular mechanisms that determine these effects of omentin-1. A decrease in serum omentin-1 levels can be considered as an independent predictor of CAD and correlates with the severity and prognosis of this disease. A number of studies have established an association between the carriage of various variants of the omentin-1 (ITLN1) gene, CAD and obesity. The article analyzes the available data on the role of the level of omentin-1 in CAD, determined not only in the blood, but also in subcutaneous and visceral adipose tissue. The possible prospects for the use of various molecules capable of increasing the level of omentin-1 in the blood are analyzed.

Conclusion. A decrease in the level of omentin-1 may be an independent predictor of CAD and is associated with the severity and progression of the disease. It is likely that omentin-1 can act as an alternative diagnostic tool to ensure optimal management of patients with CAD. Studies of the effect of omentin-1 on the prognosis in patients with various forms of CAD are largely ambiguous and therefore further, more comprehensive studies are needed.

Aim. Based on current literature data, to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD), to consider the pathophysiological mechanisms underlying this relationship, and to indicate methods for reducing cardiometabolic risk in patients with NAFLD.

Key points. NAFLD occupies a leading position in the structure of chronic liver diseases, is one of the manifestations of metabolic syndrome and is closely associated with CVD. The relationship between the prevalence of NAFLD and CVD has been established in numerous studies. CVD is significantly more severe in patients with NAFLD. A number of meta-analyses have documented a direct association between NAFLD and cardiovascular mortality. Many pathophysiological mechanisms of development of these two diseases coincide. Some molecular changes that play an important role in NAFLD are also involved in the formation of CVD. Patients with NAFLD often have atherosclerosis, which also underlies the formation of CVD.

Conclusion. All modern international and Russian recommendations for the management of patients with NAFLD pay significant attention to the advisability of CVD screening and the need to reduce cardiometabolic risk in patients with NAFLD through lifestyle modification (optimizing diet, weight loss, increasing physical activity), using statin medications, ursodeoxycholic acid and ademetionine.

Aim. To describe modern approaches to the diagnosis and treatment of prediabetes.

Key points. Taking into account the growing number of patients with prediabetes, timely diagnosis of this condition is necessary. In case of confirmation of carbohydrate metabolism disorders, active treatment is extremely important already at the stage of prediabetes, the effect on various links of pathogenesis. The management of such patients implies, first of all, an active lifestyle change and a decision on the appointment of drug therapy. When choosing a treatment option for prediabetes, it is important to take into account the type of carbohydrate metabolism disorder. With impaired fasting glycemia, metformin is a more pathogenetically justified option, and with impaired glucose tolerance – Subetta.

Conclusion. The substrate, normalizing the indicators of postprandial glycemia and the level of glycated hemoglobin in patients with prediabetes (impaired glucose tolerance), may contribute to reducing cardiovascular risks. However, there are currently no such studies, and therefore it seems relevant to carry out work evaluating the effect of therapy with this drug on the risk of cardiovascular events in patients with prediabetes.

Aim. What glucose level is associated with the occurrence of new cases of diabetes mellitus 2 type (T2DM).

Design. Prospective cohort study.

Materials and methods. A survey of a representative sample of Novosibirsk residents was carried out in 2003–2005 as part of the international project Health, Alcohol and Psychosocial factors in Eastern Europe. The presented work included indicators of 3146 people aged 45–69 years without a previous history of carbohydrate metabolism disorders (all individuals with established T2DM at the time of the initial examination were excluded from the analysis). The study included people without a history of diabetes, examined in 2003–2005 and again in 2015–2018. New cases of T2DM were diagnosed in 2003–2021. According to epidemiological criteria, diabetes was established when the fasting blood glucose level was ≥ 7.0 mmol/l, according to the anamnesis and the City Diabetes Registry.

Results. Initially, elevated fasting glucose concentrations (5.6–6.9 mmol/l) were detected in 45.3% of participants (28.5% — 5.6– 6.0 mmol/l, hyperglycemia 6.1–6.9 mmol/l — 16.8%). According to dynamic observation data, by 2021, 316 (10.1%) people will be diagnosed with T2DM. The threshold blood glucose value that determines the risk of developing T2DM over time is 5.7 mmol/l, Se = 64.2%, Sp = 61.4%, AUC = 0.67.

Conclusion. According to our data, among residents of Novosibirsk aged 45–69 years without diabetes, the prevalence of fasting hyperglycemia is high (5.6 mmol/l or more). Glucose level 5.7 mmol/L is the threshold value associated with new cases of T2DM in people 45–69 years of age.

Aim. To study telomerase activity, lipidemia and to assess the severity of atherosclerotic lesions of the brachiocephalic arteries in asymptomatic patients of working age with subclinical hypothyroidism.

Design. A cross-sectional cohort study.

Materials and methods. Data on 131 patients of working age (32 men and 99 women) with different hormonal status of the thyroid gland (thyroid) without clinical signs of chronic cerebral circulatory insufficiency were analyzed. Based on the assessment of the hormonal status of the thyroid gland, 2 groups of patients were formed: 87 with laboratory-confirmed hypertension (thyroid-stimulating hormone level > 4.0 mMU/l with normal characteristics of free fractions of thyroid hormones) and 44 patients without thyroid dysfunction. The groups formed were comparable in age, gender composition, presence and severity of hypertension, aggravated family history of early cardiovascular events, and smoking. All patients underwent ultrasound examination of the brachiocephalic arteries, determination of the lipid spectrum and telomerase concentration. The processing of the obtained data was carried out using statistical packages Excel, Statistica v. 10.0. The data obtained were interpreted as reliable, and the differences between the indicators were considered significant when the error-free prediction value was equal to or greater than 95% (p < 0.05).

Results. In the group of people with hypothyroidism, the proportion of people with multivessel atherosclerotic lesion was higher (34.5% (n = 30) vs. 13.6% (n = 6) (χ2 = 6.37; p < 0.05)), one or a combination of several signs of instability of atherosclerotic plaque (41.4% (n = 36) vs. 18.2% (n = 8) (χ2 = 7.05; p < 0.01)). In patients with subclinical hypothyroidism, precerebral atherosclerosis occurs against the background of atherogenic type IIa secondary hyperlipidemia (67.8% (n = 59) vs. 34.1% (n = 6) (χ2 = 13.52; p < 0.001) in combination with insufficiency of antiatherogenic high density lipoproteins (74.7% (n = 65) vs. 45.5% (n = 20) (χ2 = 10.98; p < 0.001)), lower values of telomerase concentration in comparison with the group of people without thyroid dysfunction: (8.2 (7.4–9.5) vs. 10.8 (10.1–12.2) ng/ml (p < 0.001)). The relationship between the level of telomerase activity (r = –0.72; p < 0.05) and the presence of subclinical hypothyroidism, atherosclerotic lesions of the precerebral bed in patients (r = –0.33; p < 0.05) was established.

Conclusion. In clinically healthy patients of working age with newly diagnosed, medically uncorrected subclinical hypothyroidism, the proportion of persons with ultrasound signs of multivessel atherosclerotic lesions of the brachiocephalic arteries is higher, and precerebral atherosclerosis occurs against the background of atherogenic type IIa secondary hyperlipidemia in combination with insufficiency of antiatherogenic high density lipoproteins, lower values of telomerase activity in comparison with the group of persons without thyroid dysfunction. Etiopathogenetic mechanisms of "early vascular aging", the criteria for stratification of risk groups for atherosclerosis-associated cardiovascular disease, the choice of diagnostic algorithms for visualizing preclinical stages of atherogenesis, and timely antiatherogenic tactics in asymptomatic patients with comorbid thyroid pathology require further study. Verification of a stenosing hemodynamically significant or non-hemodynamically significant atherosclerotic lesion of the coronary basin, regardless of the clinical component, is a factor of high cardiovascular risk requiring immediate correction of hyperlipidemia.

Aim. To evaluate the effect of dulaglutide, a glucose-lowering drug from the group of glucagon-like peptide 1 receptor (GLP-1) agonists, on indicators of fat metabolism and irisin.

Design. Open pilot study.

Materials and methods. 85 people (56 women, 29 men) with type 2 diabetes mellitus and obesity of varying severity took part in the study. 17 of them had a history of myocardial infarction, 2 patients had stroke (acute cerebrovascular accident), and all the rest had arterial hypertension. All patients were prescribed dulaglutide, a GLP-1 agonist, for ongoing glucose-lowering therapy for the purpose of intensification.

Results. After 12 months of therapy, a statistically significant (р < 0.05) decrease in anthropometric parameters was obtained: body weight decreased from 110 (70–185) to 105.5 (60–159) kg, waist circumference decreased from 124.5 (46.4–150) to 119 (90–146) cm. The levels of glycated hemoglobin statistically significantly decreased — from 7.1% (5.4–10.6%) to 6.5% (6.2–12.4%) (р < 0.05), total cholesterol — from 4.89 (2.07–15) to 4.55 (2.19–8.33) mmol/l (р < 0.05), leptin — from 32.9 (14.9–127.6) to 24.5 (13.5–133.7) ng/ml (р < 0.05), C-reactive protein — from 3.37 (0.01–64.2) to 2.24 (0.01–54.1) mg/ml (р < 0.05), the HOMA β level statistically significantly increased — from 80 (4–359) to 110 (12.2–755) (р < 0.05). In addition, the thickness of epicardial fat according to echocardiography significantly decreased — from 11 (2.5–20) to 10 (7–15) mm (р < 0.05), as well as the amount of adipose tissue according to bioimpedance measurements from 52.3 (26.6–99.8) to 44.7 (28.2–73.9) kg (р < 0.05).

Conclusion. In patients with type 2 diabetes and obesity, therapy with GLP-1 agonist dulaglutide after 12 months contributed to a significant improvement in glycemic control and pancreatic β-cell function. In patients with type 2 diabetes and obesity, therapy with GLP-1 agonist the dulaglutide after 12 months, a significant decrease in body weight, the amount of adipose tissue, and epicardial fat was observed. Regression of adipose tissue according to bioimpedansometry data was accompanied by a significant decrease in the level of leptin, a marker of inflammation C-reactive protein, and a tendency to increase the level of adiponectin and irisin.

Aim. Present two clinical cases of Maturity-Onset Diabetes of the Young, which is based on the presence of pathogenic variants in the glucokinase (GCK) gene — GCK-MODY; to characterize behavioral and cardiometabolic risk factors for diabetes complications.

Key points. In the first clinical case, the pathogenic variant p.Trp257Ter (c.770G>A, NM_000162.5) of the GCK gene, previously described in the literature, was identified in the proband and his father, in the second — the pathogenic variant p.Cys271Ter (c.1113C>A, NM_000162. 5) GCK gene. Probands are young men, 22 and 21 years old, respectively. They were first diagnosed with diabetes in the ages of 10 and 6 years during routine examinations. There were no clinical symptoms of hyperglycemia; they did not take and do not currently take hypoglycemic drugs. When examined 11 and 15 years after the diagnosis of diabetes, in each patient the level of C-peptide was within the reference values, which indicates the preservation of the secretory function of pancreatic β-cells. Antibodies were negative, the level of glycated hemoglobin (HbA1c) was 5.7 and 6.1%, respectively. No complications of diabetes were identified in either patient. The fathers of probands from both families had HbA1c levels of 6.4 and 6.5%, respectively. The father of the proband from the first clinical case does not comply with recommendations for a healthy lifestyle and nutrition, and does not deny weekly alcohol consumption. Upon examination, he was found to be overweight, arterial hypertension, dyslipidemia, steatohepatitis, and atherosclerosis of the brachiocephalic vessels, which increase the risk of cardiovascular events. The father of the proband from the second clinical case follows recommendations for a healthy lifestyle. During the examination, body weight, blood pressure, blood lipids are within the target range.

Conclusion. Presenting two clinical cases and family histories of patients with GCK-MODY, the authors note that the compliance with the principles of a healthy lifestyle, assessment and correction of the main risk factors will help avoid the emergence and progression of complications in patients with GCK-MODY. When monitoring and treating patients with diabetes of any type, it is important to follow the principles of preventive medicine.

Aim. To demonstrate the development of severe bone and visceral manifestations of primary hyperparathyroidism in a patient with a parathyroid adenoma, without complaints until the occurrence of a low-traumatic femoral neck fracture.

Key points. Fibrocystic osteitis is a severe disabling manifestation of primary hyperparathyroidism. Early diagnosis has certain difficulties due to the variability of clinical manifestations, the lack of calcium screening at the outpatient stage and the low alertness among doctors in related specialties regarding primary hyperparathyroidism.

Conclusion. Delayed diagnosis of primary hyperparathyroidism can lead to disability and a significant decrease in the quality of patients’ lives. Thus, it is extremely important to be alert to this disease, especially in young patients with signs of bilateral nephrocalcinosis, low-traumatic fractures. It is also vital to raise awareness about the primary hyperthyroidism among doctors specializing in adjacent fields.

Aim. To describe two clinical cases of obese female patients with primary infertility who underwent sleeve gastrectomy.

Key points. The presented clinical cases demonstrate the multidirectional impact of bariatric surgery on ovarian reserve indicators in two patients of reproductive age with primary infertility, comparable in degree of obesity and concomitant diseases. In both patients, 12 months after surgery, body weight was successfully reduced and carbohydrate metabolism levels were normalized. However, in the first patient, the level of anti-Mullerian hormone (AMH) increased slightly, and pregnancy occurred, while in the second patient, on the contrary, the level of AMH decreased compared to the preoperative level, and the desired pregnancy did not occur at the time of writing.

Conclusion. Literary data on the impact of bariatric surgery on women's reproductive function are scarce and contradictory. Determining the contribution of metabolic surgical interventions to restoring ovarian reserve, normalizing AMH levels and overcoming infertility will allow individualizing treatment tactics in obese patients.