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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; P0.0001), creatinine level (r=0.467; P0.0001) and negative with GFR (r= -0.436; P0.0001) 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; р0.0001). 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.

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 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.

This study aims to establish relationships between inflammatory status, ferrokinetics and lipid metabolism in patients with diabetes mellitus. Subclinical inflammation was assessed by levels of high-sensitive C-reactive protein, tumor necrosis factor-&alpha, and erythrocyte sedimentation rate. Iron metabolism parameters included complete blood count, serum iron, transferrin and ferritin. Metabolic status assessment included lipid profile, glycated hemoglobin and microalbuminuria measurement. As a result of the study it was possible to establish both general (universal) and diabetes mellitus (DM) type-dependent relationships between the parameters of lipid profile and metabolic control in DM. High-density lipoprotein cholesterol (HDL-C) levels negatively correlated with microalbuminuria (r = &minus, 0.293, p ˂ 0.05 for type 1 diabetes and r = &minus, 0.272, p ˂ 0.05 for type 2 diabetes). Ferritin concentration positively correlated with triglyceride level (r = 0.346, p ˂ 0.05 for type 1 diabetes and r = 0.244, p ˂ 0.05 for type 2 diabetes). In type 1 diabetes, a negative correlation was discovered between estimated glomerular filtration rate (eGFR) and LDL-C (r = &minus, 0.480, p ˂ 0.05), very low-density-lipoprotein cholesterol (VLDL-C) (r = &minus, 0.490, p ˂ 0.05) and triglycerides (r = &minus, 0.553, p ˂ 0.05), and a positive one between C-reactive protein concentration and triglyceride level (r = 0.567, p ˂ 0.05). Discovered relationships between lipid profile indices, inflammatory status and microalbuminuria confirmed mutual influence of hyperlipidemia, inflammation and nephropathy in diabetes patients. Obtained results justify the strategy of early hypolipidemic therapy in patients with diabetes mellitus to prevent the development and progression of microvascular complications.

Hepcidin, a hormone regulating iron metabolism, has received attention for its role in the pathogenesis of dysregulations in carbohydrate metabolism. Hepcidin disorders in patients with diabetes mellitus are bi-directional: manifesting as iron overload syndrome in cases of decreased hepcidin production and as anaemia of chronic disease in cases of hepcidin hypersecretion. However, till date, detailed analyses of mechanisms underlying hepcidin dysregulation have not been conducted nor have the interactions of ferrocinetic and carbohydrate-metabolic disorders been examined. An association between diabetes mellitus and neurodegenerative diseases as well as the role of iron metabolism in Alzheimer or Parkinson diseases is a subject of ongoing research. This review provides a summary of the current understanding of hepcidin regulation and its disorders in various diseases, including diabetes mellitus and neurodegenerative diseases. In addition, we provide an overview of the available therapies that address ferrocinetic disorders resulting from the dysregulation of hepcidin.

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.

Serum concentrations of cytokines (IL-2, IL-6, IL-8, IL-10, GM-CSF, IFNγ, TNFα) were determined in blood serum of pregnant women with different types of metabolic disorders, i.e., gestational diabetes, obesity, and a combination of those disorders. The study was performed by means of flow fluorimetry, using a multiplex test system. Changes of cytokine profiles in pregnant women with overweight or obesity, and pregnant women with gestational diabetes showed some similarities. In pregnant women with overweight or obesity we have found an increase in blood concentrations of IL-2, IL-6, IL-10, IFNγ, and TNFa. Meanwhile, an increase in blood levels of IL-2, IL-6, IL-10 and TNFα was revealed in pregnant women with gestational diabetes. The changes in cytokine profile were most pronounced in cases of pregnancy complicated with gestational diabetes and obesity. In these women, increased IL-6, TNFα, GM-CSF and IFNg concentrations were revealed in blood, along with low contents of IL-2 and IL-10. Potential causes and consequences of suggested subclinical inflammation in pregnant women are discussed. We conclude that pregnant women with metabolic disorders may develop a subclinical inflammation at the early stages of obesity, or metabolic disturbances.

Aim . To establish the diagnostic value of liquid and traditional cytological diagnosis with immunocytochemical (ICC) detection proteins (galectin-3, nucleophosmin, Ki-67) in the preoperative diagnosis of well-differentiated thyroid cancer and analysis of the effect of the autoimmune process in the thyroid gland in the diagnostic accuracy. Materials and methods . The traditional liquid-based cytology was performed on 107 samples and immunocytochemistry performed on 56 samples with histological findings: colloid goiter in 24 cases, 4 cases of Hashimoto’s thyroiditis, 4 cases of follicular adenoma, 22 cases of papillary cancer. Results . The results of a comparison of cytological and histological findings. The results of studies of diagnostic accuracy expression of galectin-3, nucleophosmin, Ki-67 for the diagnosis of thyroid cancer. A formula was developed to help determine the presence of malignancy in thyroid with high accuracy. Conclusion . The diagnostic accuracy of the method of liquid-based cytology is higher than the traditional method of cytology. ICC expression of Ki-67 method has 81.8% of sensitivity and 100% of specificity for the preoperative diagnosis of thyroid cancer. Conjoint definition HS Ki-67 and liquid-based cytology increases the sensitivity and specificity of the diagnosis of well-differentiated thyroid cancer preoperative to 100%. There no detected relations between the expression of galectin-3, NFM, Ki-67 and the presence an autoimmune process in the thyroid.

The article reviews the available data on investigations in the field of electrolyte (calcium, magnesium), hormonal (insulin, leptin) and hemostasis disturbances in term newborns from women with gestational diabetes; possible mechanisms of their development are also highlighted. The review describes changes in blood glucose concentration in term newborns from women with gestational diabetes, and their impact on the child's condition. In addition to already known factors causing macrosomia and other metabolic disorders in term neonates, the role of leptin (peptide hormone that regulates energy metabolism) is quite discussable. Low leptin levels lead to the development of obesity. It is also confirmed, that leptin influences brain development of the newborn, leading to later cognitive deficits in children from women with GDM. The aim of the review is to summarize the available data on investigations in the field of electrolyte (calcium, magnesium), hormonal (insulin, leptin) and hemostasis disturbances in term newborns from women with gestational diabetes.

The review provides information on the molecular genetic mechanisms for the development gestational diabetes mellitus (GDM). It gives data on the genetic identity of GDM and type 2 diabetes mellitus and considers a role of some adipokines and incretin hormones in the development of GDM. There is evidence for the role of magnesium and vitamin D deficiencies in the pathogenesis of gestational carbohydrate metabolic disturbances.В обзоре представлены сведения о молекулярно-генетических механизмах развития гестационного сахарного диабета (ГСД). Приводятся данные о генетической идентичности ГСД и сахарного диабета 2-го типа. Рассматривается роль некоторых адипокинов и гормонов инкретиновой системы в развитии ГСД. Приведены данные относительно роли дефицита магния и витамина D в патогенезе развития гестационных нарушений углеводного обмена.

Aims. To determine sensitivity and specificity of glycated hemoglobin (HbA 1c ) test with direct immunoturbidimetry as a method to diagnose gestational diabetes (GD). Materials and Methods. 74 pregnant females were recruited during initial screening. Glycemic disorders were diagnosed with two methods: oral glucose tolerance test with 75 g of glucose and glycated hemoglobin test. Results. HbA 1c test with direct immunoturbidimetry is a highly sensitive method for diagnosis of glycemic disorders of pregnancy, provided that cut-off level is lowered to 5.5%. Conclusion. Mild anemia was not found to have a significant impact on diagnostic value of HbA 1c test.

Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm. Results. At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.