INTRODUCTION: The development of iron overload syndrome may be due to both hereditary and acquired factors. The danger of this condition is manifested in the irreversible loss of parenchymatous pool as a result of cirrhotic transformation and marked fibrosis, caused by the consequent accumulation of iron complexes, of such important internal organs as the liver and heart. The amount of iron in the body is assessed by detecting serum ferritin concentration or by measuring liver and heart iron concentration by biopsy (LIC — liver iron concentration; HIC — heart iron concentration). Insufficient diagnostic significance of the serum ferritin concentration criterion, as well as the invasiveness and traumatization of biopsies, are limitations to the widespread use of these methods. OBJECTIVE: The purpose of this review is to present the main etio-pathogenetic factors of iron overload, the impact of this metabolic disorder on the body, and to reflect the basic principles of diagnosis and the leading role of quantitative MRI in the assessment of iron overload of vital internal organs. MATERIALS AND METHODS: Performed literature search in Russian and English languages for the period from 2001 to 2022 years in Medline/PubMed, RINC/Elibrary, CyberLeninka, Google Scholar databases by keywords: iron overload syndrome, liver, liver cirrhosis, ferritin, hemosiderin, MR diagnostics iron overload, MR relaxometry, R2*/T2*, thesaurismoses, magnetic resonance tomography, SIR (signal intensity ratio), LIC (liver iron concentration), biopsy, chronic diffuse liver diseases, DIOS. RESULTS: The final analysis included 27 publications devoted to various etio-pathogenetic aspects of iron overload syndrome. The forms of iron complexes residence in liver parenchymatous tissue are presented. Characteristics of MR-signal behavior depending on the severity of inhomogeneity of the magnetic field created by iron complexes are characterized. The areas of application of magnetic resonance imaging scanning modes for detection and quantitative diagnostics of iron overload are reflected. CONCLUSION: The ferritin-iron complex, also called ferrihydride, has high paramagnetic properties that provide high contrast MR images in the state of tissue iron overload. The leading methods for quantitative assessment of iron overload are the signal intensity ratio (SIR) method and T2*/R2*-relaxometry. Advantages and disadvantages of these methods, consisting in the limits of determining the degree of overload, make it possible to cover a wide range of overload values by complementing each other. Also the influence of parenchyma architectonics disturbances and concomitant accumulation diseases contribute to the formation of diagnostic inaccuracies. Therefore, the development of complex qualitative-quantitative MR diagnostics in order to isolate highly selective biomarkers will play an important role in MR diagnostics of iron overload syndrome.

Background: Hyperferritinemia associated with obesity and insulin resistance is a link between the components of the metabolic syndrome and a possible triggering factor in the pathogenesis of carbohydrate metabolism disorders and dyslipidemia.Aim: To establish possible relationships between ferrokinetic parameters, parameters of lipid and carbohydrate metabolism in overweight and obese patients, and to analyze the possibility of using iron metabolism parameters (ferritin and serum iron) as predictors of carbohydrate metabolism disorders in this cohort of patients.Material and Methods. The study included 52 overweight or obese patients. In the course of the study, patients were stratified into groups depending on the presence of carbohydrate metabolism disorders (CMD), and depending on the state of iron metabolism. Among all patients included in the study, an assessment of anthropometric data, a study of glycated hemoglobin, a standard glucose tolerance test with 75 g of glucose, a study of hematological parameters, as well as biochemical parameters of iron metabolism – the concentration of serum iron, transferrin and ferritin, was carried out.Results. Patients with CMD – impaired glucose tolerance or impaired fasting glycaemia – had significantly higher serum ferritin levels than obese patients without CMD (p = 0.019). In persons with a high level of ferritin, CMD developed significantly more often than in patients with a ferritin content in the range below the 75th percentile (χ2 = 5.278, p = 0.022). According to the ROC analysis, ferritin showed a rather high sensitivity – 75%, and specificity – 84.4% at a diagnostic threshold of 126.65 ng/ml (area under the curve = 0.738; p = 0.016) in the diagnosis of prediabetes (IGT/IFG) in overweight and obese individuals.Conclusion. High concentrations of iron and ferritin are positively associated with CMD, with ferritin being a promising predictor of prediabetes and type 2 diabetes mellitus.

The purpose of the study was to evaluate the severity of changes in the values of markers-candidates for the differential diagnosis of anemia of chronic diseases in patients with type 1 and type 2 diabetes mellitus. The total number of leukocytes, erythrocyte sedimentation rate, content of C-reactive protein, TNFa, ferritin and hepcidin were evaluated. 50 people with type 1 diabetes mellitus and 81 people with type 2 diabetes mellitus were examined. The diagnosis of anemia was established on the basis of data on the level of hemoglobin, the content of erythrocytes in the blood, ferritin and serum iron. Next, the type of anemic syndrome was determined. The patients were divided into groups: 14 patients with diabetes mellitus and anemia of chronic diseases, 15 people with diabetes mellitus and iron deficiency anemia, 38 patients with diabetes with latent iron deficiency and 64 patients with diabetes mellitus without anemia. The comparison group consisted of 17 healthy volunteers. It was shown that in the general sample of patients with diabetes mellitus anemia of chronic diseases was distinguished only by the erythrocyte sedimentation rate, which was higher than in iron deficiency anemia, latent iron deficiency and in patients without anemia. The severity of inflammation in diabetic patients was analyzed depending on its type. The concentration of hepcidin in the blood of diabetic patients, regardless of type, exceeded its content in the blood of healthy individuals. Elevated serum concentrations of TNFα were characteristic of inflammation in type 1 diabetes mellitus. Diabetes mellitus type 2 was characterized by an increase in: erythrocyte sedimentation rate - relatively healthy individuals; concentrations of C-reactive protein - in comparison with healthy volunteers and patients with type 1 diabetes mellitus; ferritin levels compared with patients with type 1 diabetes mellitus. Taking into account the type of diabetes and the type of iron metabolism disorder, it was found that in type 1 and type 2 diabetes mellitus, only the erythrocyte sedimentation rate in patients with anemia of chronic diseases was significantly higher than in patients with iron deficiency anemia and without anemia. The article discusses the reasons for the difficulties in using inflammatory markers (ferritin and hepcidin) as parameters for verifying anemia of chronic diseases in patients with diabetes mellitus. It is pointed out that it is necessary to take into account the differences in the mechanisms of inflammation development in type 1 or type 2 diabetes mellitus when trying to use cytokines and C-reactive protein as additional diagnostic markers in practice. The rationale is given for the prospects of determining the erythrocyte sedimentation rate, with the recommendation of a certain threshold value, for the detection of anemia of chronic diseases in patients with type 1 and type 2 diabetes mellitus.

Iron affects the pathogenesis and clinical course of several chronic metabolic diseases such as obesity, atherosclerosis, non-alcoholic fatty liver disease and type 2 diabetes mellitus. High pro-oxidant iron activity is physiologically controlled by mechanisms regulating entry, recycling, and loss of body iron. These mechanisms include the interplay of iron with ferritin, transferrin, hepcidin, insulin, as well as with adipokines and proinflammatory molecules. An imbalance of these regulatory mechanisms results in both systemic and parenchymal siderosis. Iron overload has a toxic effect on the major tissues involved in lipid and glucose metabolism — pancreatic β cells, liver, muscle, and adipose tissue — as well as the organs affected by chronic hyperglycemia — brain, retina and kidneys. Hyperferremia leads to a decrease in insulin secretion, the formation of insulin resistance and increased liver gluconeogenesis. Molecular mechanisms for these effects are diverse. Elucidating them will implicate both for carbohydrate metabolism disorders prevention and for the pathogenesis of other diseases that are, like diabetes mellitus type 2, associated with nutrition, aging and iron. The literature review presents data from world studies on the mutual influence of glucose metabolism and iron overload, and discusses the differences between hereditary and acquired disorders of iron metabolism from the standpoint of their influence on carbohydrate metabolism.

The aim of this review was to provide extended information on current trends in the diagnosis of complicated diabetic foot syndrome (DFS), the most frequent and severe complication of diabetes mellitus, including hightech medical imaging methods and instrumental and laboratory predictors of the complicated course and risk of amputation in DFS.The article provides an analytical review of modern publications over the past 5 years on diagnosis and therapy. Pilot data on the use of high-tech medical imaging methods, assessment of skin microbiota and ulcers in DFS, molecular testing methods in terms of predicting the amputation risk and survival of patients with DFS, as well as the effectiveness of biosensing systems have been systematized, summarized, and subjected to analytical evaluation.The review provides an expert assessment of the capabilities of pathogen-specific molecular imaging using modern positron emission tomography (PET), single-photon emission computed tomography (SPECT), and highenergy radionuclides in bacterial infection to understand its pathogenesis, minimize diagnostic problems, improve antimicrobial treatment, and address fundamental and applied aspects of DFS. Literature data on the assessment of foot perfusion in diabetic patients with varying degrees of limb ischemia by hybrid technologies (SPECT / CT and PET / CT) and new modalities of magnetic resonance imaging (MRI) are also systematized, which contributes to new understanding of the response to revascularization, surgical shunting, and stimulation of angiogenesis within ischemic tissue, as well as potentially to healing of foot ulcers.The review is aimed at substantiating a multidisciplinary approach in DFS, selection, development, and implementation of innovative strategies for diagnostic modalities to identify diabetic foot pathologies, and choice of an adequate method for treating and monitoring the results of therapy in the context of personalized medicine.

Erythrocyte morphology is a reflection of both physiological and pathological reactions occurring in the body of patients with diabetes mellitus (hyperglycemia, adipose tissue dysfunction, dyslipidemia, lipid peroxidation, angiopathy, diabetic nephropathy, etc.). There are no available data in the literature that would characterize gradual and progressive changes in the morphology of the erythron system in patients with diabetes mellitus, the more so any analysis of the relationships with pathogenetic factors affecting them.Aim. The aim of the study was to evaluate the nature of erythrocyte index relationships with vascular and metabolic complications of type 1 and type 2 diabetes mellitus. The main objective of the study was to determine the changes in red blood cell indices at different stages of diabetic microangiopathies and in the presence of different indicators of metabolic control.Material and Methods. A total of 122 patients were enrolled in a single-stage, single-center, comparative, controlled study. Patients were assigned to three groups: group 1 comprised patients with type 1 diabetes mellitus (n = 41); group 2 comprised patients with type 2 diabetes mellitus (n = 67); and group 3 comprised control patients (n = 14). Statistical processing of the results was performed using the SPSS Statistics 20 software.Results. Patients with diabetes mellitus are characterized by qualitative changes in the erythron system manifesting as changes in red blood cell indices.The study identified the significant associations between the changes in erythron system (erythrocyte indices) and various phenotypic features of patients with type 1 and type 2 diabetes mellitus, namely: the duration of diabetes of over 10 years, type 2 diabetes mellitus in combination with obesity, and the presence of dyslipidemia, diabetic retinopathy, and poorly controlled diabetes mellitus if glycated hemoglobin exceeded 8% with a subsequent corresponding increase per each 1%.Conclusion. Additional studies are required to implement these markers, in particular, a red cell distribution width, as risk factors for unfavorable prognosis i.e. the risk of developing various diabetes mellitus complications.

IV (XXVII) Национальный конгресс эндокринологов с международным участием «ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ЭНДОКРИНОЛОГИИ» 22-25 сентября 2021 года ПОДХОДЫ К ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКЕ АНЕМИЧЕСКОГО СИНДРОМА У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ Мусина Н .Н ., Саприна Т

IV (XXVII) Национальный конгресс эндокринологов с международным участием «ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ЭНДОКРИНОЛОГИИ» 22-25 сентября 2021 года ОСОБЕННОСТИ ФЕРРОКИНЕТИКИ И ПАРАМЕТРОВ СИСТЕМНОГО ВОСПАЛЕНИЯ У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ Мусина Н .Н ., Саприна Т

The aim of the research was to establish the role of inflammation mediators and iron metabolism in the pathogenesis of various types of anemic syndrome in pregnant women with gestational diabetes mellitus (GDM). Materials and methods. 32 pregnant patients with GDM were examined; 14 of them had iron deficiency anemia, 18 – anemia of chronic diseases. The enzyme-linked immunosorbent assay was used to determine the concentration of IL-6, hepcidin and a soluble receptor for transferrin in the blood serum of pregnant women, the concentrations of C-reactive protein and transferrin were determined with the method of turbidimetry. Results. It was shown that women with GDM had higher IL-6 level compared to healthy pregnant women, and the concentration of IL-6 did not depend on the type of anemic syndrome. The C-reactive protein concentration was higher in patients with GDM and anemia of chronic diseases than in healthy pregnant women or in pregnant women with iron deficiency anemia. An analysis of iron metabolism markers in pregnant women with GDM established that patients with anemia of chronic diseases had higher hepcidin levels than women with iron deficiency anemia or healthy pregnant women. Conclusions. We established the heterogeneity of the anemic syndrome in pregnancy complicated by GDM. It was confirmed that GDM was accompanied by subclinical inflammation, which was more pronounced in anemia of chronic diseases. The research showed that the mechanism of development of anemia of chronic diseases involving the hepcidin protein was also realized in GDM, characterized by subclinical inflammation. The results indicate the importance of establishing the type of the anemic syndrome in pregnant women with GDM for effective therapeutic follow-up.

Fulminant type 1 diabetes mellitus is a subtype of diabetes mellitus. It is characterized by the extremely rapid development of hyperglycemia and ketoacidosis because of the near-total destruction of pancreatic -cells. A clinical case of lethal, type 1, fulminant diabetes mellitus is presented. The patient management strategy and possible causes of the adverse course and outcome of the disease are analyzed.

The database contains data on patients with diabetes mellitus and disorders of carbohydrate metabolism - anthropometric data, data on the state of metabolic control parameters, data on the state of iron metabolism and lipid metabolism.

BACKGROUND: It is known that metabolic disorders in diabetes mellitus have a regulating effect on ferrokinetics, and therefore diabetes mellitus is often accompanied by various disorders of iron metabolism, both anemia and secondary iron overload. The main problem is timely and accurate differential diagnosis between anemia of chronic diseases and iron deficiency anemia. It is necessary to establish reliable laboratory markers of anemia of chronic diseases in order to solve this problem, as well as to understand what metabolic disorders can lead to the occurrence and aggravate the course of this type of anemia. AIMS: To study the frequency of occurrence of violations of ferrokinetics in patients with diabetes mellitus, as well as to establish clinical and biochemical correlations that are significant in the differential diagnosis of various disorders of iron metabolism: iron deficiency anemia, anemia of chronic diseases and dysmetabolic iron overload syndrome in diabetes mellitus. MATERIALS AND METHODS: The research design a single-stage observational single-center research. The research was conducted on the basis of the endocrinological clinic of the Federal State Budgetary Educational Institution of Higher Education Siberian State Medical University in Tomsk. The research included 76 patients with type 1 and type 2 diabetes mellitus. We conducted an assessment of all patients as follows: anthropometric data assessment; glycated hemoglobin study; creatinine level study with the calculation of glomerular filtration rate (GFR) using the CKD-EPI formula. We also evaluated the number of erythrocytes, reticulocytes, the hemoglobin concentration, haematocrit level and biochemical parameters of iron metabolism: serum iron and ferritin concentrations; the concentration of hepsidin and non-specific markers of inflammation: erythrocyte sedimentation rate (ESR) and highly sensitive C-reactive protein (CRP). RESULTS: 20 people (26.3%) of the 76 patients included in the study, had type 1 diabetes mellitus and 56 people (73.3%) had type 2 diabetes mellitus. The parameters of ferrokinetics did not significantly differ in patients with type 1 and type 2 diabetes mellitus, while in the group of patients with 20 patients (26.3%) from the 76 ones included into the research had type 1 diabetes mellitus and 56 (73.3%) from them had type 2 diabetes mellitus. The parameters of ferrokinetics did not significantly differ in patients with type 1 and type 2 diabetes mellitus, while in the group of patients with type 2 diabetes mellitus, the levels of CRP (p=0.034) and blood leukocytes (p=0.020) were significantly higher than in patients with type 1 diabetes mellitus. Both in the main group of patients with impaired carbohydrate metabolism, and in patients with type 2 diabetes mellitus, anemia of chronic diseases prevailed in the structure of the anemia syndrome. After dividing the main group of patients into groups by type of anemia syndrome: absence of anemia, anemia of chronic diseases and iron deficiency anemia, a comparative analysis of the average values of markers of inflammation and the level of hepsidin in these groups was performed. It was found that in patients with anemia of chronic diseases, the level of hepsidin is significantly higher than in patients without anemic syndrome (p=0.033). Paired correlation analysis showed a positive correlation of ESR with microalbuminuria (r=0.515; P<0.0001), creatinine level (r=0.467; P<0.0001) and negative — with GFR (r= -0.436; P<0.0001) and iron in serum (r=-0.276; p=0.017). As the result of ROC analysis the most informative in the diagnosis of anemia of chronic disease were: ferritin — sensitivity 78%, specificity 52% with a diagnostic threshold of 75.5 ng/ml (area under the curve 0,695; p=0.006); ESR — sensitivity 67%, specificity 64% with a diagnostic threshold of 15.5 mm/HR (area under the curve of 0.750 in; p=0.040) and the CRP — sensitivity 67%, specificity 64% with a diagnostic threshold of 5.2 ng/ml (area under the curve 0,646; р<0.0001). CONCLUSION: Thus, the studied markers of inflammation — ESR and CRP, as well as hepsidin in combination with the classic diagnostic parameter — ferritin, demonstrated high value in the diagnosis of anemia of chronic diseases and can be included in the modified algorithm for differential diagnosis of anemia syndrome in patients with diabetes mellitus.

The aim of the research was to establish the role of inflammation mediators and iron metabolism in the pathogenesis of various types of anemic syndrome in pregnant women with gestational diabetes mellitus (GDM).Materials and methods. 32 pregnant patients with GDM were examined; 14 of them had iron deficiency anemia, 18 – anemia of chronic diseases. The enzyme-linked immunosorbent assay was used to determine the concentration of IL-6, hepcidin and a soluble receptor for transferrin in the blood serum of pregnant women, the concentrations of C-reactive protein and transferrin were determined with the method of turbidimetry.Results. It was shown that women with GDM had higher IL-6 level compared to healthy pregnant women, and the concentration of IL-6 did not depend on the type of anemic syndrome. The C-reactive protein concentration was higher in patients with GDM and anemia of chronic diseases than in healthy pregnant women or in pregnant women with iron deficiency anemia. An analysis of iron metabolism markers in pregnant women with GDM established that patients with anemia of chronic diseases had higher hepcidin levels than women with iron deficiency anemia or healthy pregnant women.Conclusions. We established the heterogeneity of the anemic syndrome in pregnancy complicated by GDM. It was confirmed that GDM was accompanied by subclinical inflammation, which was more pronounced in anemia of chronic diseases. The research showed that the mechanism of development of anemia of chronic diseases involving the hepcidin protein was also realized in GDM, characterized by subclinical inflammation. The results indicate the importance of establishing the type of the anemic syndrome in pregnant women with GDM for effective therapeutic follow-up.

The purpose of the present study was to specify a role of inflammatory mediators in pathogenesis of various types of anemia in pregnant obese women. We determined IL-1, IL-6, TNFα, C-reactive protein and hepcidin concentrations in blood serum of pregnant women with obesity depending on the type of anemic syndrome, either iron-deficiency anemia, or anemia of chronic diseases. We showed that the content of IL-6 in blood of the obese women exceeds the value of this index in healthy pregnant women (p < 0.05), and it does not depend on the presence and type of anemic syndrome. We found that the C-reactive protein concentration in pregnant women with obesity is higher than reference values (p < 0.05). Moreover, the contents of C-reactive protein in blood serum of pregnant women with anemia of chronic diseases is significantly higher (p < 0.05) than in women with iron deficiency anemia. Hepcidin concentration in blood of pregnant women with obesity and anemia of chronic disease was a specific feature: its content was significantly higher than in healthy pregnant women (p < 0.05), or in pregnant women with anemia-free obesity (p < 0.05). Hepcidin levels also exceeded 2-fold its contents in serum from pregnant women with obesity and iron deficiency anemia (p < 0.05). We have found that only pregnant women with obesity and anemia of chronic diseases have shown a positive correlation between the concentrations of C-reactive protein and blood levels of hepcidin (r = 0.733, p < 0.05), or IL-6 (r = 0.679, p < 0.05).The discussion concerns potential mechanisms of evolving anemia of chronic disease combined with subclinical inflammation in pregnant women with metabolic disorders. We conclude that a combination of obesity with gestational diabetes is a risk factor of anemia of chronic diseases in pregnant women. Development of an algorithm for differential diagnosis of iron deficiency anemia and anemia of chronic diseases in this cohort of patients is advisable for future studies in the area.