An interview with Professor Aleksander Sergeevich Ametov, Dr. of Med. Sci., Head of the Chair of Endocrinology, Head of the Network Chair of the UNESCO on the topic “Bioethics of diabetes mellitus as a global challenge” at the Russian Medical Academy of Continuing Professional Education of the Ministry of Health of Russia; lead research associate at S. P. Botkin City Clinical Hospital of the Moscow Healthcare Department; Honoured Scientist of the Russian Federation. An interview with Professor Aleksander Sergeevich Ametov, Dr. of Med. Sci., Head of the Chair of Endocrinology, Head of the Network Chair of the UNESCO on the topic “Bioethics of diabetes mellitus as a global challenge” at the Russian Medical Academy of Continuing Professional Education of the Ministry of Health of Russia; lead research associate at Botkin Hospital. Aleksander Sergeevich told us that metabolic health is a global characteristic, which is related not only to obesity. Metabolic health is programmed in utero. Metabolic health management is a priority task. During the interview, we touched upon the capabilities of the state and other public institutes to change the trend of an increasing number of patients with diabetes mellitus, changes in the mentality of endocrinologists, the role of endocrinologists in a multidisciplinary team. Professor Ametov emphasised the role of recent knowledge on antihyperglycemics, which made it possible to significantly reduce mortality and incapacitation due to their added cardioprotective and renoprotective effects. 

Metabolic health is a key factor in prevention and management of the majority of chronic conditions. Metabolic health prevention is a priority area of the modern healthcare, and it requires a comprehensive approach, which includes identification of the risk factors, lifestyle modification, search for new possible ways to correct the risk factors, and cooperation of various specialists for the benefit of the patient.

Aim. To identify the features of gene expression of de novo synthesis enzymes and ceramide (Cer) degradation enzymes in fat depots of various localization in patients with cardiovascular diseases, depending on age.

Design. A single-center prospective clinical study.

Materials and methods. 60 patients with coronary artery disease (CAD) were examined. Biopsies of subcutaneous (SAT), epicardial (EAT), and perivascular adipose tissue (PVAT) were obtained during coronary bypass surgery. Gene expression of de novo Cer synthesis enzymes (C1 and C2 subunits of serine palmitoyltransferase — SPTLC1, SPTLC2; ceramide synthase 1–6 — CERS1–6; dihydroceramide desaturase — DEGS1) and degradation of Cer (acid ceramidase — ASAH1, sphingomyelin synthase 1 and 2 — SGMS1 and SGMS2,) were evaluated using quantitative polymerase chain reaction.

Results. The expression of Cer de novo synthesis enzyme genes is maximal in the ventricular tract of persons 75 years and older, with a high level of CERS5 and CERS6 (producing Cer14:0 and Cer16:0) in EAT — in persons 60–74 years old. The highest expression of the CERS2 gene (synthesizing Cer 20:0, 22:0, 24:0, 24:1, 26:0) in EAT, it was observed in the group of people aged 60–74 years, in PVAT — 75 years and older. Increased expression of the ASAH1 gene (degradation of Cer to sphingosine and free fatty acids) was detected in patients 75 years and older, SGMS1 and SGMS2 genes (conversion of Cer to sphingomyelin) — in persons 60–74 years of age in all AT. These results indicate the modulation of synthesis and accumulation of Cer in the AT ventricular localization with age.

Conclusion. The AT of patients with coronary heart disease differed in the level of expression of de novo synthesis enzyme genes and Cer degradation depending on age. It is likely that the AT ventricular localization undergoes deeper age-related remodeling, which can lead to the accumulation of Cer in the EAT and PVAT.

Aim. To identify predictors of unfavorable course of coronary artery disease (CAD) in patients who underwent coronary artery bypass grafting (CABG).

Design. Prospective observation.

Materials and methods. A prospective observation of 24 months to identify predictors of unfavorable course of CAD included 98 patients who underwent CABG. Median age — 63 (56; 68) years. The concentration of blood plasma glucose, lipid parameters, insulin, uric acid, fatty acid binding protein 4 (FABP4) in the blood serum, the insulin resistance index, the level of expression of microRNA-21 in the blood plasma and myocardium, relative level of messenger RNA FABP4 gene in epicardial and subcutaneous adipose tissue were determined. The development of angina pectoris, myocardial infarction (MI), bypass thrombosis/functionally significant bypass restenosis, increase in myocardial dysfunction, acute ischemic cerebrovascular accident, and death were taken as the major adverse cardiac events (MACE).

Results. Over the course of 24 months, 15 (15.3%) patients (11 men (73.3%) and 4 (26.7%) women) with CAD who underwent CABG achieved the MACE. The median follow-up time before the occurrence of MACE was 11.1 (10.5; 11.9) months. Among all MACE, 7 patients had a fatal outcome, 3 had shunt thrombosis, 4 had hemodynamically significant stenosis of an artery that had not previously undergone bypass/stenting and underwent percutaneous coronary intervention, 1 had an acute ischemic cerebrovascular accident. The risk of the onset of MACE in patients with CAD who underwent CABG was determined by such factors as type 2 diabetes mellitus, the presence of zones of impaired local myocardial contractility, and the risk of the most “hard” end point — death, in addition to these factors was associated with obesity, hyperuricemia, with the onset of CAD with MI and an increase in the level of FABP4 in the blood serum. Increasing serum FABP4 levels significantly reduces the risk of death.

Conclusion. In patients with CAD who have undergone CABG, the most significant factors determining the onset of MACE during the first 24 months are type 2 diabetes mellitus and the presence of zones of impaired local myocardial contractility, which, along with such factors as obesity, hyperuricemia, and a history indicating the onset of CAD with MI and an increase in serum FABP4 levels are associated with an increased risk of death.

Aim. To study the role of lipid metabolism gene polymorphism and changes in the lipid-transporting lipid system in patients with moderate to severe preeclampsia (PE).

Design. Prospective cohort comparative study.

Materials and methods. We analysed results of clinical, anamnestic and laboratory examination of 130 patients with a high risk of PE, following a prenatal diagnostics performed during the first trimester. The patients were divided into three groups: with actual severe PE (group I, n = 53, weeks 23 to 38 of pregnancy); with actual moderate PE (group II, n = 45, weeks 28 to 40 of pregnancy), and without PE (control group, or group III, n = 32, weeks 28 to 40 of pregnancy).

During the clinical examination, somatic and obstetric-gynaecological history was taken, and the present pregnancy was reviewed. A sample for blood biochemistry was drawn upon hospitalisation; the analysis included lipid parameters (cholesterol, triglycerides, high, low and very low-density lipoproteins), total bilirubin, urea, creatinine, apolipoproteins (АроА, АроВ). Sample genotyping was performed using the realtime polymerase chain reaction with a reagent kit and protocol for genetic polymorphisms.

Results. The results show that the most informative parameters of dyslipidaemia in pregnant women, which are associated with the risk of PE, are high levels of very low-density lipoproteins, atherogenic index of over 3.5 and ApoB/ApoA index of over 0.9.

The presence of allele T of polymorphic locus ApoE rs429358 in homo- or heterozygous state in the genotype increases the risk of PE, while genotype СС of polymorphism ApoE rs429358 has a protective effect against this pathology. Genotype AA of polymorphism rs708272 of gene CETP (G>A) has also a protective effect, while the presence in the genotype of at least one variant of allele G of this locus increases the risk of PE.

Conclusion. The study demonstrates the importance of lipid transport system parameters, especially the ratio of apolipoproteins and various density lipoproteins, as well as polymorphisms ApoE T>C, CETP G>A in the pathogenesis and diagnosis of PE.

Aim. To evaluate hypolipidemic therapy in real clinical practice, the frequency of achieving target lipid values and the reasons for ineffective treatment of dyslipidemia.

Design. Retrospective prospective nonrandomized single-center continuous study.

Materials and methods. From 8655 persons referred to any department of Sechenov University, we selected those with documented dyslipidemia and patients prescribed or receiving lipid-lowering therapy. In the end, we selected 3812 patients. In the course of our work, we called all patients. Among those who agreed to participate in the study, we interviewed them: whether they were taking hypolipidemic agents, whether they controlled lipid spectrum parameters, whether they had cardiovascular complications (CVC), and concomitant pathologies. The risk of CCO was assessed during the telephone interview. All patients who required evaluation were invited for consultation at the Center. A total of 3282 patients' data were obtained.

Results. A total of 805 (24.5%) people out of 3282 agreed to be observed at our Center. 130 (16.2%) patients were regularly monitored by a cardiologist at the place of residence. Hypolipidemic therapy was received by 240 (29.8%) of respondents. It turned out that those with higher cardiovascular risk were less likely to reach target lipid values. The mean total cholesterol was 9.2 ± 5.9 mmol/L, LDL — 6.4 ± 3.7 mmol/L, and triglycerides — 2.8 ± 5.6 mmol/L. There were no people with low cardiovascular risk among our sample. The high-risk group included 292 (36.3%) patients, very high risk — 313 (38.9%), and extreme high — 72 (8.9%). In the high- and very high-risk subgroups, 6 and 7% of participants had target lipid levels before the start of follow-up at our Center, and there were no such patients in the extreme high-risk subgroup. Of 805 patients, 590 (73.3%) required correction of the regimen or initiation of hypolipidemic therapy. Among statins, rosuvastatin (n = 218, 36.9%), mean dose — 22.5 mg/day; atorvastatin (n = 165, 28%), mean dose — 56 mg/day; combination of rosuvastatin with ezetimibe at a dose of 10 mg/day (n = 124, 21%) and combination of atorvastatin with ezetimibe at a dose of 10 mg/day (n = 83, 14.1%) were used.

Conclusion. According to our study, the large number of patients have not achieved target lipid levels and the low percentage of patients with proven contraindications to the prescription of lipid-lowering therapy make it necessary to work more actively with patients for primary and secondary prevention of atherosclerosis by prescribing statins.

Aim. To study the incidence and risk factors associated with asthenia in patients with type 2 diabetes mellitus (DM2) in real-time clinical practice.

Design. Cross-sectional clinical study.

Materials and methods. 2373 patients were examined for symptoms of asthenia in outpatient settings; these patients were followed up by primary care physician therapeutics for chronic non-communicable diseases (CNCD). A group of DM2 patients (n = 527) was separated from this cohort.

All patients were interviewed; their medical information was collected; their systems and organs were examined; and medical records were reviewed. A diagnosis of CNCD was confirmed on the basis of results and current clinical recommendations. Asthenia and its intensity were identified using the Multidimensional Fatigue Inventory 20 (MFI-20) and Fatigue Severity Scale (FSS).

Results. The incidence of asthenia in DM2 patients was 38.52 % (n = 203) on MFI-20 and 26.76 % (n = 141) on FSS. The most common disorders on MFI-20 were: General Asthenia (20.11 %; n = 106), Physical Asthenia (16.13 %; n = 85) and Hypoactivity (13.09 %; n = 69). Presence of symptoms of asthenia in DM2 patients was associated with elderly age (60.0 (48.0; 68.0) vs. 53.0 (45.0; 64.0) years old in patients without asthenia; р < 0.0001) and multimorbidity: a history of acute myocardial infarction was observed in 7.88 % of patients with asthenia vs. 0.62 % of patients without asthenia (p < 0.00001), acute cerebrovascular accident — 5.91 % vs. 0.31 % (p < 0.0001), malignancies — 15.76 % vs. 1.54 % (p < 0.000001). DM2 patients with symptoms of asthenia were more often smokers vs. patients without asthenia (30.05 % and 20.68 %, respectively; p < 0.05), monitored their blood pressure regularly (65.02 % and 49.07 %; p < 0.001), took antihypertensives (45.32 % and 25.00 %; p < 0.00001) and statins regularly (34.48 % and 15.74 %; p < 0.00001).

Conclusion. Asthenia is common in DM2 patients seeking outpatient medical assistance. Age-associated multimorbidity requiring longterm sophisticated treatment strategies and constant control of a number of parameters is probably one of the causes of asthenia in this patient category.

Aim. To assess the risk of chronic cardiac failure (CCF) in young patients with metabolic syndrome.

Key points. Materials were searched in RSCI (Russian Science Citation Index), PubMed, Clinical Evidence, Cochrane Library, which allow for fast and efficient search for systematic reviews and prevent systemic errors.

Assessment of the risk of CCF development in young people, especially those with metabolic syndrome, is crucial for informed decisionmaking. In order to identify groups with a higher risk of CCF in young people, a screening algorithm is needed, which accounts for modifiable risk factors and heredity. Currently, there is no patient-specific algorithm to assess the estimated CCF development in young patients with various risk factors.

Conclusion. An important task is to develop and standardise patient-specific risk measures for CCF in the young population, primarily for those with metabolic syndrome.

Aim. To consider modern views on risk factors and progression of chronic heart failure (CHF), the main causes of hyperammonemia, the clinical and pathogenetic relationship of hyperammonemia and CHF and approaches to patient management.

Key points. CHF is one of the leading cardiovascular problems today. The prevalence of CHF varies from 0.3% in people aged 20–29 years to 70% in people over 90 years old. In the case of progressive HF, it may be necessary to have a heart transplant or long-term mechanical circulatory support, as well as palliative care, which also requires significant costs. Heart failure with preserved left ventricular ejection fraction (accounts for about 50% of all CHF cases. An increase in the ammonia content in the blood causes a high probability of developing multiorgan dysfunction. Reference levels of ammonia levels in human blood are not definitively regulated by international documents. The normal values mainly depend on the technique and the reagents used. The formation of hyperammonemia is a multifactorial process. The main causes are liver malfunction. In the structure of all causes of hyperammonemia, the proportion of the liver cirrhosis is about 90%, and non-cirrhotic causes — about 10%. Many mechanisms of non-cirrhotic hyperammonemia have been described. Non-cirrhotic hyperammonemia may be the result of increased pressure in the hepatic veins, which can lead to damage to hepatocytes and an increase in serum ammonia levels. To date, researchers are particularly interested in the development of hyperammonemia against the background of taking anticonvulsants. Under the influence of ammonia, the expression of myostatin increases, which reduces the growth of muscle mass, at the same time, muscle proteolysis is activated. Since the myocardium is a muscle tissue, similar processes in cardiomyocytes are not excluded. It has been proven that patients with HF have higher ammonia levels than those without it. The use of L-ornithine-L-aspartate is one of the main strategies for the correction of hyperammonemia.

Conclusion. At the moment, there is a need for further study of the combination of CHF and hyperammonemia, the mechanisms of mutual influence, as well as risk factors for the progression of CHF against the background of hyperammonemia and the problem of managing such patients.

Aim. To systematize modern data on risk factors, clinical picture, diagnostics of diabetic cardiovascular autonomic neuropathy (CAN), and to highlight the main directions of its prevention and treatment.

Key points. CAN (autonomic cardiovascular neuropathy) is a form of diabetic autonomic neuropathy in which, due to damage to sympathetic and/or parasympathetic fibers, the regulation of cardiac activity and vascular tone is impaired. Despite a significant increase in the risk of cardiovascular disease, CAN often remains unrecognized, which leads to the development of heart rhythm disturbances, vascular tone disorders and increases the risk of death from all causes. Among all forms of diabetic neuropathy, it is CAN that is associated with the highest mortality. The risk of CAN increases by 6% per year in type 1 diabetes mellitus (DM) and by 2% per year in type 2 DM. The main factor of pathogenesis is chronic hyperglycemia, leading to oxidative stress and accumulation of advanced glycation end products, which damage first the parasympathetic and then the sympathetic link of the autonomic nervous system. Damage to autonomic regulation in CAN is always characterized by persistent and, as a rule, drug-resistant disorders. Persistent tachycardia in combination with painless myocardial ischemia significantly increases the risk of death from myocardial infarction and its complications. Diagnostics of CAN is currently based mainly on functional tests that can only detect an advanced process; sensitive and specific examination methods that allow assessing the initial manifestations of CAN are only being developed. Drugs that would have proven efficacy in relation to CAN are also not registered at present, but achieving target glycemia values can significantly slow down its progression. Modern drugs with neuroprotective properties can also have a positive effect on the initial manifestations of CAN.

Conclusion. Early detection and prevention of CAN are important clinical tasks. Currently, the key factor in preventing the development and progression of CAN is maintaining normal glycemia. The study of the effect of new classes of drugs on the course of CAN is ongoing; the data obtained suggest the possibility of some preventive potential for CAN in modern hypoglycemic drugs with a neuroprotective effect. 

Aim. To demonstrate the outcome of type 2 sodium-glucose cotransporter (SGLT-2) inhibitor use in a young patient with newly diagnosed type 2 diabetes mellitus against the background of a limited amount of carbohydrates in the diet by developing of diabetic ketoacidosis (DKA).

Key points. DKA is an acute life–threatening complication of diabetes mellitus, characterized by a complex of symptoms — hyperglycemia, hyperketonemia, metabolic acidosis. It develops in situations where the metabolic need for insulin significantly exceeds its level in the body. After the introduction of SGLT-2 inhibitors into wide clinical practice, the concept of euglycemic diabetic ketoacidosis appeared, one of the triggers of which is a sharp restriction of carbohydrates in the diet against the background of the use of gliflozines.

Conclusion. SGLT-2 inhibitors are currently one of the key ones in the management of type 2 diabetes mellitus, nevertheless, in conditions of a sharp shortage of carbohydrates in the diet, they can provoke the development of diabetic ketoacidosis. For this reason, all patients receiving drugs of this group should be aware of the possible risks and trained in methods of preventing the development of complications of diabetes. 

Aim. To demonstrate the possibility of the influence of metabolic disorders on the formation of type 2 myocardial infarction in a young woman using a clinical example.

Key points. Acute myocardial infarction in young women may not be diagnosed due to low alertness of doctors and patients themselves, since this pathology is rare at this age. However, over the past decade, the prevalence of myocardial infarction in young women has increased. The presented clinical case demonstrates the development of atherosclerotic coronary lesion with critical stenosis of the coronary artery in a 31-year-old woman, which required its endoprosthetics. The lesion manifested itself with a typical clinical picture of newly developed angina, but the patient herself assessed these symptoms incorrectly, which led to late hospitalization and the development of myocardial infarction. Acute myocardial infarction was briefly preceded by an unfavorable metabolic background: impaired carbohydrate metabolism, abdominal obesity, hypothyroidism.

Conclusion. Despite the low incidence of ischemic heart disease in young women, it is necessary to be alert in the presence of myocardial ischemia symptoms in this group of patients, especially in the presence of metabolic disorders. The most important are carbohydrate metabolism disorders, abdominal obesity, and hypothyroidism. Abdominal obesity, accompanied by metabolic disorders, may be one of the possible potentially controllable risk factors for myocardial infarction in young women.