Background.
Over the past few years, special attention has been paid to achieving glycaemic control for type 2 diabetes mellitus (T2DM) patients, since it is a factor for determining the risk of developing macro- and microvascular complications of diabetes. Certain modern guidelines suggest an individual approach to the choice of HbA_1c target.
Objective.
Objective.
 .
of this study was to estimate the percentage of T2DM patients who have reached the HbA_1c levels. This was determined based on their age and the presence of severe complications.
Materials and Methods.
A total of 2195 patients with T2DM were studied. The patients were divided into the following age groups: <45, 45?64, and over 65 years. Each group was subdivided into two subgroups depending on the presence of severe complications. The target level of HbA_1c was determined according to the subjects? age and the presence of severe complications:.

• <45 years old without complications ? HbA_1c<6.5%;
• <45 years old with complications and 45?64 years old without complications ? HbA_1c<7.0%;
• 45?64 years old with complications and over 65 years old without complications ? HbA_1c<7.5%;
• over 65 years old with complications ? HbA_1c<8%.

Statistical analyses were performed using Microsoft Excel. The data are presented as mean values ? standard deviation.
Results.
The following glucose-lowering therapy techniques were used for different groups: monotherapy with diet ? 301 (13.7%) patients; oral antidiabetic drugs (OADs) ? 1335 (60.8%) patients; combined treatment using OADs with insulin ? 319 (14.6%) patients; and insulin monotherapy ? 240 (10.9%) patients. The HbA_1c target was reached for 27.3% of patients in the group aged <45 years old without complications; in the group < 45 years old with complications for 25.0% of patients; in the group of 45?64 years old without complications for 30.0% of patients; in the group aged 45?64 with complications for 35.2% of patients; in the group?65 years old without complications for 43% of patients, and in the group?65 years old with complications for 55.6% of patients.
Conclusions.
The proportion of T2DM patients who have reached the HbA_1c target value using the individual approach was higher than that using the conventional approach (HbA_1c<7.0%). A high percentage of patients did not achieve HbA_1c targets in all groups, indicating the need for antihyperglycaemic therapy.

The method of Genome-Wide Association Studies (GWAS) steadily becomes the basis for searching for candidate genes of monogenic and multifactorial diseases, including type 1 and 2 diabetes mellitus, coronary heart disease, obesity, vascular diseases, and others. To date, approximately 40 loci associated with type 2 diabetes mellitus (T2DM) have been identified and genetic predisposition factors for cardiovascular diseases have been determined. In some cases, the GWAS results not only enable understanding of the pathophysiologic basis for diseases, but also may give rise to new drugs. However, the question naturally arises about the possibility of implementing the accumulated knowledge to predict the development of diseases, including T2DM and its vascular complications. This review summarises the literature data on the possibilities to use the GWAS results to calculate the risk of developing diabetes and cardiovascular diseases. Determination of the individual genetic risk will allow for the primary prevention of diseases and will apparently be the basis of personalised predictive medicine in the near future.

Diabetes mellitus (DM) is characterised by relative or absolute insulin deficiency. The currently available treatment methods for DM cannot provide normal blood glucose level without hypo- or hyperglycaemia episodes, thus failing to completely prevent the development of diabetic complications. Replacement of ?-cells (transplantation of the pancreas or ?-cells) is accompanied by complications and requires life-long immunosuppressive therapy that is not always followed by restoration of insulin independence; there is also a substantial deficit of donors. Stem cells do not cause such negative effects and can be used in therapy to avoid such problems. Allogeneic stem cell transplantation is complicated by immune rejection of a transplant, whereas the use of embryonic stem cells is associated with ethical concerns, complicated cell line selection, and risk of teratoma formation. The present review focuses on therapeutic pathways of autologous transplantation of tissue stem cells in order to restore the ?-cell pool, for immune reconstitution and modulation of the immune response in DM patients.

Insulin resistance (IR) is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.
IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell). Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.
This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

Objective.
To evaluate morphological and functional parameters of the heart and vessels in patients with type 2 diabetes mellitus (DM2) and diabetic cardiovascular autonomic neuropathy (CAN).
Materials and methods.
A total of 139 patients with DM2 and hypertension (mean age: 53.1?4.9 years; mean duration of hypertension: 9.7?7.8 years) were included in this study. Based on cardiovascular autonomic function test results (electrocardiography, heart rate variability) patients were divided into 2 groups as follows: Group 1 included 40 patients without CAN and Group 2 included 99 patients with CAN. The control group comprised 30 patients with hypertension and normal carbohydrate metabolism (mean age: 53.1?6.0 years; mean duration of hypertension: 10.9?8.5 years). All patients underwent ultrasonography of the heart and common carotid artery.
Results.
Group 2 patients showed a significant decrease in maximal transmitral flow velocity during early diastolic filling (0.61?0.12 m/s) and a decrease in maximal transmitral flow velocity during late diastolic filling (0.65?0.11 m/s) compared with Group 1 patients (0.66?0.09 m/s and 0.69?0.09 m/s, respectively, р <0.05) and control group patients (0.71?0.16 m/s and 0.69?0.14 m/s, respectively, р <0,05). Further, Group 2 patients showed a significant increase in left ventricular mass and ventricular end-diastolic volume (253.3?67.2 g and 120.6?25.2 ml, respectively) compared with control group patients (204.6?72.7 g and 110.4?22.2 ml, respectively, р <0.05) and a significant increase in intima-media complex thickness (IMT) (1.28?0.15 mm) compared with Group 1 patients (1.17?0.19 mm, р = 0.004).
Conclusion.
Increased left ventricular mass and heart volume parameters (end-systolic volume and end-diastolic volume), left ventricular diastolic dysfunction and increased common carotid artery diameter caused by increased IMT are the main determinants of CAN in patients with diabetes.

Objective.
To determine the levels of fibroblast transforming growth factor (TGF?1), basic fibroblast growth factor (?-FGF), markers of nonspecific inflammatory response (interleukin-6 (IL-6)), C-reactive protein (CRP), advanced glycation end-products (AGEs) and their receptors (RAGEs) and to study their effect on the intima-media complex (IMC) thickness in patients with coronary heart disease (CHD) and type 2 diabetes, depending on carbohydrate metabolism compensation.
Materials and Methods.
37 patients with CHD underwent a general clinical examination, analysis of the carbohydrate and lipid metabolism parameters and the renal function, and also were evaluated with instrumental methods of analysis (echocardiography, coronary angiography and duplex scanning of the brachiocephalic arteries). To determine the level of the analyzed parameters, blood samples were taken from the aorta during coronary angiography and concomitantly from the cubital vein in all patients.
Results.
The presence of diabetes mellitus (DM) in patients with CHD was found to be associated with a more severe atherosclerotic disease of the coronary and brachiocephalic vessels. A direct correlation between the degree of stenosis and the level of fibroblast growth factors, inflammatory factors, and advanced glycation end-products was found. A direct correlation between AGE and TGF?1 and the lipid metabolism parameters was established. A statistically significant elevation of the studied parameters in the arterial and venous blood of patients with DM was revealed.
Conclusion.
These findings confirm the relationship between connective tissue disorders and lipid metabolism in the pathogenesis of atherosclerosis. A negative effect of hyperglycaemia on atherosclerotic changes of the vascular wall was demonstrated.

Background.
Quality of life is a multivariate indicator of patient?s perception of various aspects of his/her own life. Questionnaires (specific and non-specific) are used to assess it.
Objective. .
To validate the Russian version of the specific quality of life questionnaire ?NeuroQol? in diabetic patients with peripheral polyneuropathy.
Materials and Methods.
A total of 371 diabetic patients participated in the study. All patients were screened for the signs of peripheral neuropathy and limb ischemia. The examination results were used to evaluate the eligibility of a patient; the eligible patients were then asked to fill in the quality of life questionnaire. The validation included translation, pilot testing and assessment of reliability and validity.
Results.
Cronbach?s alpha coefficient of internal consistency exceeded 0.8 in all scales and proved the high reliability of the questionnaire. Criterion validity was analyzed by Spearmen correlation (r) coefficient between the domains and external parameters. The results obtained revealed significant correlation between NeuroQol domains and neuropathy severity, which indicates adequate criterion validity. The psychometric assessment (construct validity) was performed using factor analysis. The physical and psychosocial factors contributing to the quality of life were identified; they confirmed the validity of the questionnaire structure.
Conclusion.
The results demonstrate that the Russian version of the NeuroQol questionnaire is valid and reliable. This questionnaire enables one to assess quality of life in patients with the signs of peripheral diabetic polyneuropathy, including evaluation of the efficiency of various treatment strategies for complications. The lack of social life and psychological conditions of patients affect their quality of life more than physical complications do. These parameters must become the focus of specialists' attention in their efforts to improve the quality of life in this category of patients.

Independently of causes and risk factors of hypoglycaemia, its manifestations are always unfavourable and evoke fear and other negative emotions that lead to negative consequences connected with quality of diabetes control. The fear of hypoglycaemia creates an internal conflict by diminishing patients? motivation to adhere to intensive treatment regimes. In addition to the severity of hypoglycaemia and its negative consequences, quality of life is one of the main criteria for evaluating the physical, psychological and social components of patient's life as a whole. Fear of hypoglycaemia is one of the most important factors; it either directly or indirectly affects quality of life and influences all aspects of the patient's life. Fear of hypoglycaemia is also a source of anxiety for the patient's relatives, causing damage to their familial and social relations. The negative consequences of hypoglycaemia can affect the relationship between spouses, as well as between parents and children with type 1 diabetes. The qualitative and quantitative data demonstrate that non-severe nocturnal hypoglycaemia causes more anxiety and fear in patients than daytime hypoglycaemia does. To quantify the fear of hypoglycaemia in adults with type 1 diabetes, the hypoglycaemia fear scale (HFS) was developed and still is the most commonly used instrument. To assess the fear of hypoglycaemia in children and their parents, the HFS scale was adapted to be used in the paediatric population: HFS for parents (PHFS) and HFS for children (CHFS). From a clinical point of view, these scales for measuring the level of fear of hypoglycaemia may be useful for monitoring adult patients and families who may need additional support, training or assistance in dealing with issues related to hypoglycaemia. The methods for regulating the fear of hypoglycaemia range from behavioural to pharmaceutical and surgical ones, and include a broad range of activities. Nevertheless, the problem remains quite relevant today and an integral approach for solving this problem, both by the physician and by the patient, should be used. Proper assessment of the patient's level of anxiety, impact of the fear of hypoglycaemia on his or her social life, awareness of the possible psychological consequences of this problem may positively affect both the behaviour and mood of the patient, and the opportunity to achieve better glycaemic control.

The routine approach to evaluating the effectiveness of diabetes treatment based on the level of glycated haemoglobin (HbA.
_1c) accounts for the average glucose level but does not consider the scope and frequency of its fluctuations. The development of computational methods to analyse glycaemic oscillations has made it possible to propose the concept of glycaemic variability (GV). The interest in research focused on GV increased dramatically after continuous glucose monitoring (CGM) technology was introduced, which provided the opportunity to study in detail the temporal structure of blood glucose curves. Numerous methods for assessing GV proposed over the past five decades characterize glycaemic fluctuations as functions of concentration and time and estimate the risks of hypoglycaemia and hyperglycaemia. Accumulating evidence indicates that GV may serve as a significant predictor of diabetic complications. Prospective studies demonstrate that certain GV parameters have independent significance for predicting diabetic retinopathy, nephropathy and cardiovascular diseases. There is evidence that GV correlates with the severity of atherosclerotic vascular lesions and cardiovascular outcomes in diabetic patients. The mechanisms underlying the relationship between GV and vascular complications are being intensively studied, and recent data show that the effect of GV on vascular walls may be mediated by oxidative stress, chronic inflammation and endothelial dysfunction. Average blood glucose levels and GV are considered independent predictors of hypoglycaemia. Increased GV is associated with impaired hormonal response to hypoglycaemia and is a long-term predictor of hypoglycaemia unawareness. These data allow us to conclude that computational methods for analysing GV in patients with diabetes may serve as a promising tool for personalized assessment of glycaemic control and the risk of vascular complications and hypoglycaemia. Thus, the reduction of GV can be regarded as one of the therapeutic targets to treat diabetes.

Background.
Impairment of the central nervous system manifested as cognitive dysfunction caused by metabolic or structural changes is a severe progressive vascular complication of type 1 diabetes mellitus (T1DM). Significant difficulties in the diagnosis of cognitive dysfunction are associated with subjective diagnostic techniques.
Objective.
To identify the role of neurospecific markers in the diagnosis of cognitive dysfunction in patients with T1DM.
Materials and Methods.
A total of 58 patients with T1DM aged 16?30 years were included in this study. The control group included 29 healthy young adults matched by gender and age. The survey included clinical and laboratory examinations, psychological testing and magnetic resonance imaging (MRI) of the brain. The Montreal Cognitive Assessment (MoCA) was used to screen for cognitive impairment. The levels of neurospecific proteins (S100, glial fibrillary acidic protein and myelin basic protein) were determined to identify early markers of cognitive impairment. MRI of the brain was performed using a Siemens Magnetom 1.0 T system to assess structural changes in the central nervous system.
Results.
The study revealed increased levels of all neurospecific proteins, which correlated with parameters of hyperglycaemia and cognitive deficit (MoCA scores of <26 points). MRI of the brain revealed signs of grey matter atrophy and involvement of white matter, which correlated with the presence of chronic hyperglycaemia, cognitive impairment and microvascular complications.
Conclusion.
Chronic hyperglycemia can be involved in the pathogenesis of cognitive dysfunction in T1DM patients. More studies (prospective controlled and observational trials) are needed to clarify the relationship of diabetes and central nervous system impairment.

Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba?) is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more) non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

This review analyses existing literature, including authors' own data, describing the results of clinical trials which assess safety and efficacy of insulin Glargine (Lantus?) in children and adolescents, as well as peculiar features of T1D management in this age group, including the challenge of reducing the rate of hypoglycemia while maintaining adequate glycemic control. The article also discusses various issues in T1D management in children and adolescents, including the role of glycemic control in development of vascular complications, hypoglycemia and the variability of glycemia. The data confirm the high efficacy of Lantus insulin in respect to metabolic control, including the decrease in the incidence of hypoglycemia and in variability of glycemic profile, the safety of its clinical use in treatment of children, including young children, and adolescents, as well as its ability to improve the quality of life for patients and their parents.

Objective.
The objective of this study was to identify the ways to optimize therapy for metabolic syndrome through complex clinical and economic analysis.
Methods.
Sixty patients with metabolic syndrome were included in the study. The study group (30 subjects with the mean age of 41.0?11 years, 23 females (76.7%), 7 males (23.3%)) received pharmacotherapy for obesity (orlistat) and insulin resistance (metformin), lipid-lowering therapy and antihypertensive therapy, if needed. The control group (30 patients with the mean age of 43.4?9.5 years, 26 females (86.7%), 4 males (13.3%)) received lipid-lowering and antihypertensive therapy, if needed. All patients underwent clinical and laboratory examination, assessment of depression (Beck Depression Inventory) and evaluation of the quality of life using the SF-36 questionnaire at admission to the study and after 6 months of therapy. Complex clinical and economic analyses, including cost-effectiveness and cost-utility analyses and calculation of such indices as ?the incremental cost-effectiveness ratio? (ICER), LYG, QALY and ?net monetary benefit? (NMB), were conducted based on the results obtained.
Results.
Improvement of clinical and laboratory indicators and quality of life in the study group was more significant than that in the control group. The direct medical costs were 33,440.40 RUB for the study group and 18,878.50 RUB for the control group (for 6 months of therapy). The control group CER was 4,016.70, while the study group CER was 3,125.30; ICER was 2,430.90 RUB. LYG was equal to 0.7 and 2.3 years for the control and the study groups, respectively. The QALY measure for the control and study groups was 8.63 and 9.45, respectively. The weighted average total costs for the intended period of living was 498,745.00 RUB for the control group and 457,866.00 RUB for the study group. The control group CUR was 57,792.00 and 54,902.00 RUB/QALY without and with discounting, respectively, while in the study group they were 48,451.00 and 46,029.00 RUB/QALY, respectively. The NMB for the control group amounted to 10,790,910.00 and 10,815,840.00 RUB without and with discounting, respectively, while for the study group the values were 11,904,500.00 and 11,927,390.00 RUB.
Conclusions.
The results of clinical and economic analysis show that treatment of the metabolic syndrome, including pharmacotherapy of obesity and insulin resistance, should be prioritized over mere medical advisory and lifestyle modifications.

Sexual dysfunction characterized by a significant decline in the quality of life of patients and leading to infertility and problems in social life is diagnosed in more than 40% of patients with diabetes mellitus (DM).
Erectile dysfunction is the most common sexual disorder in DM patients. The article describes epidemiology, classification, pathophysiology, diagnostic and treatment of erectile dysfunction in T1DM patients.

May 14, 2014 marks 200 years since the establishment of the Medical Department of the Imperial Kazan University (now Kazan State Medical University, KSMU). Since the XIX century, scientists of the Kazan Medical School studied physiology and pathology of the endocrine system. The first researchers were interested in the problems of endemic goitre, diabetes mellitus, and function of the adrenal glands. In 1976, the Endocrinology Department was organised in the Kazan State Medical Institute, the first among universities of the RSFSR. The head of the Department, V.V. Talantov, became the chief non-staff endocrinologist of the Ministry of Health of the Republic of Tatarstan (RT) and organiser of the Association of Endocrinologists in the RT. Moreover, he contributed to the organisation of the endocrine service in the republic and endocrinology began to be taught as an independent discipline. V.V. Talantov was a member of the Scientific Council of Endocrinology of the Russian Academy of Medical Sciences, Deputy Chairman of the Committee of Endocrinology Problems of the Ministry of Health, and a member of the editorial boards of four medical journals. The research in the field of endocrinology is now actively continued on the endocrinology course at KSMU. In-depth study of various aspects of the pathogenesis of diabetes and its complications was selected as the first-priority.