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Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, the development of which is mediated by both genetic disorders and various intracellular and extracellular molecular processes. One of the main pathogenetic mechanisms for the development of T2DM is a progressive decrease in the mass and functional reserve of β-cells, which largely determines the course of T2DM. The mechanisms of action of most sugar-lowering drugs are associated with increased secretion of insulin, so it is obvious that the effectiveness of the therapy will also largely depend on the functional state of β-cells. All this explains the great interest in studying the mechanisms of damage of β-cells in T2DM and factors that can accelerate this process, leading to their death and the development of a relative and then absolute insulin deficiency. The mechanisms of dysfunction β-cells in T2DM have not been studied much. This article provides an overview of the data of domestic and foreign literature of recent years on the molecular, intracellular features of various mechanisms of damage and death of β-cells in type 2 diabetes. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

The study of diabetes mellitus (DM), its complications and related pathologies has been continuously performed for many years; however, despite the substantial work and outstanding achievements in studying the mechanisms of DM development and the success of new medicinal products for controlling glycaemia, the problems associated with the late complications of DM continue to increase. The importance of glycaemic control in the early stages of DM for the development of complications is seen only after a sufficiently long period of observation. Such a delayed effect of primary good or unsatisfactory metabolic control, which shapes the patient’s clinical fate to a greater extent, is termed ‘metabolic memory’. The disorders developed under the influence of hyperglycaemia persist for long periods after the normalisation of carbohydrate metabolism; moreover, the effect of previous hyperglycaemia extends over the next 20 and even 30 years. Current research is focused on the possible mechanisms of metabolic memory development, including oxidative stress, advanced glycation end products and epigenetic mechanisms. This research will provide insight into potential markers for the early development and progression of vascular complications and new therapeutic possibilities for the future. However, determining the probable ‘point of no return’ is more important, which implies that a point exists; after this point is crossed, the progression of vascular complications associated with DM cannot be prevented or reversed. The results of numerous experimental studies demonstrate that the prerequisite components of metabolic memory can be used as potential markers of the progression of DM complications, and may be potential therapeutic targets.

Background. In Russia, the prevalence of diabetes continues to increase with the growing diabetes epidemic. In recent years, the paradigm of diabetes treatment has been changing, with patients increasingly becoming equal participants in the treatment process, through the introduction of self-monitoring blood glucose (SMBG). Several clinical studies have demonstrated a positive relationship between SMBG and the decline of the epidemiological and economic burden of diabetes. At present, the procurement of public funds for SMBG is below the specified level in Russia. Aims. To investigate the potential macroeconomic benefits of public health resource allocation and the use of planned state investments to fund SMBG in insulin-treated diabetic patients. Materials and methods. This study was conducted with data from insulin-treated diabetic patients. The epidemiological burden of this cohort was determined by the following indicators: the number of patients and the incidence of complications resulting from diabetes, disability, mortality, age and sex. The economic benefits were evaluated by the implementation of two measures: (1) procurement of public funds for the purchase of means for SMBG in patients with insulin-treated diabetes and (2) the use of highly accurate blood glucose metres. To evaluate economic burden, the epidemiological burden was translated into monetary terms using cost-of-illness. Economic benefits were defined as reductions in economic burden. Results. The economic benefits of public-funded blood glucose test strips for insulin-treated diabetic patients exceeded the required additional investments for their purchase by 1.5 fold. A significant reduction in the inaccuracy of blood glucose metres from 20% to 10% may reduce the economic burden by 9.36 billion RUB. The combined state benefits from the implementation of both measures would significantly decrease the economic burden of diabetes to 29.2 billion RUB. Conclusions. Increased procurement of public funds for SMBG in insulin-treated diabetic patients would bring economic benefits that far exceed the required investments.

Hypogonadism in male patients is defined as a decrease in the serum testosterone level; it is associated with specific symptoms and/or signs (see the detailed description below). It is a common complication in diabetes mellitus. The guidelines do not review all disorders leading to the development of hypogonadism but focus on options for the treatment of hypogonadism, which is generally observed in male patients with diabetes. In the literature, data on the prevalence of hypogonadism in patients with diabetes are available. In the section on diagnostics, the medical history of patients with hypogonadism and diabetes, including the necessary methods for physical and laboratory inspection. Risk factors for and the clinical consequences of hypogonadism are separately considered. In the section on treatment options, variations in treatment using various androgenic therapeutic agents based on patients’ requirements, conservation of their reproductive function, and their risk factors are provided. Special attention is given to indications of, contraindications of and risk factors for androgenic therapy in male patients with diabetes, particularly those in their advanced age. The principles of the clinical monitoring are developed. The favourable effects of androgenic therapy for hypogonadism in male patients with diabetes are shown.

Aim. We analysed the main epidemiological characteristics of diabetes mellitus (DM) in the Russian Federation (prevalence, incidence, mortality and mean life span), degree of diabetes control, and prevalence of diabetic complications (retinopathy, nephropathy, and diabetic foot syndrome and macrovascular pathology) according to the federal DM registry. Materials and methods. The database of the federal DM registry of 79 regions was included using the online system until 31.12.2016. Results. TThe total number of patients with DM in the Russian Federation on 31.12.2016 was 4.348 million (2.97% of the population), comprising 4 million patients with DM2 (92%), 255,000 with type 1 diabetes (T1DM) (6%), and 75,000 with other types of DM (2%). DM prevalence per 100,000 population was as follows: T1DM, 164.19/100,000; type 2 diabetes (T2DM), 2637.17/100,000; and other types of DM, 50.62/100. The incidence per 100,000 population was as follows: T1DM, 16.15/100,000; T2DM, 154.9/100,000; and other types of DM, 8.65/100,000. Mortality per 100,000 population was as follows: T1DM, 2.1/100,000; T2DM, 60.29/100,000; and other types of DM, 0.57/100,000. Mortality decreased in patients with T1DM by 6.6% and with T2DM by 3.6%. Mean life span in patients with T1DM was 50.3 years for men and 58.5 years for women. Mean life span in patients with T2DM was 70.1 years for men and 75.5 years for women. Glycated haemoglobin A1c (HbA1c) levels in T1DM was

Aim.To evaluate the prevalence of undiagnosed type 2 diabetes mellitus (T2DM) among patients with cardiovascular disease.Materials and methods.T2DM screening programs among patients with cardiovascular disease were held from 2013 to 2014 in several Russian cities. In total, 1001 patients aged ≥40 years with hypertension and/or atherosclerotic disease and without prior diagnosis of T2DM were screened in outpatient cardiology clinics. T2DM diagnosis was based on fasting plasma glucose levels, glycated haemoglobin (HbA1c) and/or oral glucose tolerance test (OGTT) results. Blood pressure (BP), family history of T2DM, cardiovascular disease, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were analysed.Results.Fasting glucose was measured in 1000 (99.8%) patients, HbA1c was measured in in 623 (62.2%) and OGTT was performed in 286 (2.6%). Fasting glucose detected 8% of newly diagnosed T2DM; among patients who underwentHbA1c measurement, the prevalence of T2DM was 10.91%, and among patients who underwent OGTT, the prevalence was 13.99%. Depending on the chosen test, the prevalence of undiagnosed pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) was in the range of 14.4%–36.4%. The majority of patients with T2DM diagnosed by OGTT did not have target blood pressure and lipid levels; 67.5% had elevated systolic BP, 47.5% had elevated diastolic BP, 90.9% had high LDL (≥1.8 mmol/l) and 52.9% had high triglyceride levels (≥1.7 mmol/l).Conclusion.A high prevalence of undiagnosed T2DM (from 8% to 13.99%, depending on the diagnostic criteria) and pre-diabetic state in patients with cardiovascular disease may require screening for T2DM in this high-risk group.

Objective.To estimate annual expenditures attributed to diabetes mellitus (DM) per patient in Russia based on data from epidemiologic studies and to analyse DM cost drivers.Methods.The expenditures per diabetic patient were calculated as the sum of medical costs (outpatient and emergency room visits, inpatient care and medications provided during outpatient care), payments for sick leaves, disability pensions and gross domestic production (GDP) losses due to temporary disability (indirect costs). All data on resource consumption and productivity losses were derived from the dataset for Russia, collected from the point of view of a multicentre international study on the practice of DM treatment. Medication costs were based on registered governmental price lists (list of vital and essential drugs). Medical care costs were estimated using the approved public health care reimbursement rates. Disability payments were calculated on the basis of data published by the Russian Pension Fund and Social Security Fund. GDP losses were assessed using federal statistics.Results.The mean total annual costs per patient with DM type 1 (T1) were 81.1 thousand Russian rubles (RUR) and those per patient with DM type 2 (T2) were 70.8 thousand RUR. Although most patients with DMT2 were >60 years, approximately 25% of costs were nonmedical and caused by productivity losses; for patients with DM type 1(T1), this proportion was 35%. The medical cost structure differed depending on the type of diabetes. In T1, the main component was attributed to DM treatment; in DMT2, almost half of medical costs were due to DM complications. Medication costs accounted for 69% and inpatient care accounted for only 22% of medical costs in DMT1. For DMT2, the proportion spent on inpatient care (43%) was almost equal to medication costs (46%). Mean expenditures per patient with DM complications were higher; in the case of DMT2, the presence of complications increased the costs by 3 times. Mean medical costs were higher for patients not reaching the target level of Hb1Ac than those reaching it, despite age or the presence of complications. The results of regression analysis showed that the strongest predictors of costs growth were the number of admissions, presence of complications and insulin treatment. It was also demonstrated that the mean medical cost per patient with uncomplicated DM T2 on insulin therapy was 38.5 thousand RUR, which was comparable to the cost per patient with complications, receiving other glucose-lowering treatment (37.0 thousand RUR).Conclusion.Costs for patients with DM complications are considerably higher than those for patients without complications. Therefore, the key point in controlling the growth of the DM economic burden is to minimise and/or prevent the development of DM complications, which could be achieved by timely DM diagnosis and appropriate glucose-lowering therapy.

Intensification of antihyperglycaemic treatment in patients with poorly controlled type 2 diabetes mellitus who were on insulin therapy remains a difficult issue. Results from clinical trials with the sodium-glucose linked transporter (SGLT-2) inhibitor dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus using insulin are summarised and discussed in the article.

Despite the increase in the number of hypoglycemic agents, 35%–40% of patients with diabetes are unable to achieve adequate glycemic control. One of the reasons is the genetic heterogeneity of diabetes mellitus, requiring different treatment approaches; however, the individual metabolic features and sensitivity to drugs also affect the therapeutic effectiveness. The review presents the main results of pharmacogenetic research of several antidiabetic drugs: metformin, sulfonylurea, agonists of glucagon-like peptide-1 and thiazolidinediones.

Aims. Insulin degludec (IDeg) is a novel insulin analogue that, following subcutaneous injection, forms soluble multihexamers, resulting in an ultra-long duration of action, which is two-fold longer than that of insulin glargine (IGlar). We present data from Russian cohorts of two multinational, open-label, treat-to-target phase 3 trials that investigated the efficacy and safety of IDeg and IGlar administered once daily.Materials and methods. The BEGIN Basal–Bolus Type 1 trial was a 52-week study comparing IDeg (n = 45) to IGlar (n = 16), both 100 U/mL, and in combination with insulin aspart in patients with type 1 diabetes (T1D). The BEGIN LOW VOLUME trial compared IDeg (200 U/mL; n = 27) to IGlar (100 U/mL; n = 28) over 26 weeks in insulin-naïve patients with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs. The primary outcome of both studies was the non-inferiority of IDeg to IGlar, as assessed by HbA1c level reduction at the trial end.Results. In patients with T1D, HbA1c level reductions at the trial end were 0.42% (IDeg) and 0.22% (IGlar). The rates of confirmed hypoglycaemia (plasma glucose level < 3.1 mmol/L or severe) were lower in IDeg than in IGlar [17.83 vs. 22.87 events/patient/year exposure (PYE), respectively]. The rates of nocturnal-confirmed hypoglycaemia were lower for IDeg than for IGlar (2.24 vs. 4.77 events/PYE, respectively). Severe episodes occurred in >10% of patients in both treatment groups, with rates per PYE of 0.12 (IDeg) and 0.06 (IGlar). In patients with T2D, HbA1c levels decreased by 1.17% (IDeg) and 1.26% (IGlar) at the trial end. The rates of confirmed hypoglycaemia were comparable in IDeg and IGlar (0.52 vs. 0.44 events/PYE, respectively). The rates of nocturnal-confirmed hypoglycaemia were lower for IDeg than for IGlar (0.18 vs. 0.28 events/PYE, respectively). No severe episode occurred in either treatment group. In both studies, IDeg was well tolerated with no difference in safety between the two analogues investigated.Conclusions. In both T1D and T2D, IDeg provided similar glycaemic control to IGlar, with a lower risk of nocturnal hypoglycaemia.

Aim: The aim of this study was to evaluate the efficacy and safety of the new ultra-long-acting insulin degludec (Tresiba®) in the treatment of type 2 diabetes in routine clinical practice.Methods: This primary health care clinical observational study included 20 insulin-naïve type 2 diabetic patients (mean age: 57.2 years, range: 54.4–61.5 years), who were inadequately controlled on maximum tolerated doses of oral antidiabetic drugs (OADs) and in whom baseline insulin therapy with ultra-long-acting insulin degludec was initiated. The duration of treatment was 6 months. The list of procedures met the ‘Standard of primary medical care in non-insulin-dependent diabetes mellitus’, as approved by the Ministry of Health of the Russian Federation (12.28.2012 №1581-n). Quality of life was assessed using the SF-36 questionnaire. All patients provided written consent before participating in the study.Results: In the outpatient setting, insulin degludec was well tolerated by all the patients. During the observational period, there were no events of symptomatic hypoglycaemia confirmed by self-measured plasma glucose (blood glucose level

The results from the analysis of the ADVANCE trial and post-intervention program ADVANCE-ON are presented in this article. These studies are dedicated to study the effect of intensive glycemic control on the incidence of micro- and macrovascular events in patients with type 2 diabetes mellitus and evaluation of long-term results of intensive glycemic control. We discuss the progress of views on the impact of glycemic control on the development of cardiovascular complications. According to the analysis of the research results, gliclazide MR is safe in patients with type 2 diabetes at high risk for cardiovascular complications.

Aim. Circulating progenitor endothelial cells (CPCs) play an important role in the regeneration of damaged vascular endothelium. We aimed to study the effect of type 1 diabetes mellitus (DM) on the number of different lines of CPCs.Methods. The number of different lines of CPCs was evaluated by flow cytometry in 45 patients with type 1 DM (mean age: 26,6±6,5 years) of different duration and 14 healthy volunteers.Results. The number of CPCs in the peripheral blood flow of patients with type 1 DM was significanlty reduced compared with that in healthy volunteers and had a reliable inverse correlation with glycated haemoglobin (HbA1c).Conclusions. The number of CPCs in the peripheral blood flow of patients with type 1 DM depended on the level of DM compensation. Of the different lines of CPCs, Lin-CD34+ cells were significantly reduced by 42% (p=0,006), Lin-CD34+c-Kit- cells by 42% (p=0,007) and Lin-CD34+c-Kit+ cells by 41% (p=0,022). Thus, the number of CPCs in the peripheral blood of patients with type 1 DM is reduced with higher levels of HbA1c.

Metabolic syndrome (MS) is extremely common (20%–25% of the world’s population), and its diagnostic criteria are defined and well known. It has been shown that patients who have MS are twice as likely to die from a cardiovascular complication and three times as likely to suffer from it compared with patients without MS. However, the underlying cause of MS remains to be clearly elucidated, although inherited factors, such as insulin resistance (IR), and external factors are considered to play a key role in this process. Special attention should be paid to MS in young patients, who may present the first manifestation of inherited lipodystrophy. The study describes the first known family in Russia (three clinical cases) with familial partial lipodystrophy (FPLD) type 3 caused by heterozygous p.R212Q PPARG mutation (MIM#601487). The study reports rare forms of inherited IR, such as FPLD, and contributes to a better understanding of common disorders such as MS.

Creating an "artificial pancreas" (a "closed loop" insulin pump, with self-adjusting insulin abilities, based on real time continuous glucose monitoring data) – is one of the most actual medical challenges of modern engineering and cybernetics.Artificial pancreas (AP) prototypes based on wearable insulin pump with subcutaneous insulin delivery are still problematic, mainly because of slow insulin pharmacokinetics. Intravenous insulin infusion via AP allows effectively maintain euglycaemia for inpatients, due to insulin pharmacokinetics and pharmacodynamics advantages. Unfortunately, it can’t be used for outpatients. Intraperitoneal insulin infusion is still relatively infrequently used in the world, but it is a promising alternative, compared to both previous methods due to a physiological action profile, fast insulin pharmacokinetics, relatively better safety and availability for outpatient usage.The purpose of this review is to describe the intraperitoneal insulin infusion features for diabetes patients at a point of AP creation perspectives.

Clinical and epidemiological monitoring of diabetes in Russian Federation (RF) is carried out by the National diabetes register, which methodological and organizational reference center is Federal Endocrinology Research Centre. Since 2014 initiated the translation the National diabetes register on online software system in order to increase the effectiveness of the register as a scientific and analytical platform. The article include the analysis of DM prevalence, incidence,DM-related mortality,the prevalence of diabetic complications and analysis of effectiveness of diabetes care (included HbA1c) and according to the data of online register.

The study of hereditary predisposition to multifactorial diseases is essential for diagnosis and selection of the optimal treatment. The study of polymorphisms of candidate genes whose products are involved in the pathogenesis of multifactorial diseases is of great clinical importance. Aim. The aim of this study was to investigate the association of rs2241766 and rs1501299 polymorphisms in the ADIPOQ gene, rs2275737 and rs2275738 polymorphisms in the ADIPOR1 gene and rs11061971 and rs16928751 polymorphisms in the ADIPOR2 gene with the development of type 2 diabetes mellitus (T2DM) in the Russian population. Materials and methods. The study included a group of 500 patients with T2DM diagnosed based on standard diagnostic criteria (T2DM+). The control group (T2DM-) was a random sample of 500 patients with no evidence of the disease and was matched to the T2DM+ group for gender, age and body mass index. The determination of alleles and genotypes was performed using real-time polymerase chain reaction with TaqMan probes. The X2 test and contingency tables were used to compare the distribution of allele and genotype frequencies. A p-value of

Aim. The aim of this study was to investigate late diabetic complications in patients with Type 1 diabetes mellitus (T1DM) who received simultaneous pancreas-kidney transplantation (SPK). Materials and Methods. The study included 16 patients with T1DM who received SPK. All patients underwent clinical examination and diagnostic investigation. Results. After SPK, 93.75% of the patients had a functioning pancreas transplant, and 100% had a functioning kidney transplant within 4?48 months [mean 21 months (10 is revealed; 36)). All patients had euglycaemia according to daily monitoring. The mean level of glycated haemoglobin (HbA1c) before surgery was 9.1% (range 8.7%?11%) and was 5.7% after surgery (5.55%?5.9%; p < 0.0001). The baseline level of insulin was 12.5 ?IU/ml (11.4?15.3 ?IU/ml) and the baseline level of C-peptide was 2.02 ng/ml (1.07?2.77 ng/ml). Normal renal function was observed (glomerular filtration rate 76 ml/min/1.73 m2 (68?90 ml/min/1.73 m2). Other laboratory findings included haemoglobin 127 g/l (120?130 g/l), serum parathyroid hormone 77.5 pg/ml (61?85 pg/ml), serum phosphate 1.2 mmol/l (1.07?1.3 mmol/l) and blood pressure 110(100?120)/70(64?80) mmHg. In 37.5% of the patients, vitrectomy and additional laser panretinal photocoagulation were performed for proliferative diabetic retinopathy. Other ophthalmological disorders included newly diagnosed cataract (81.25%), secondary cataract (25%) that required YAG discission in three patients, glaucoma (25%) and macular oedema (12.5%). Ulcers of the lower extremities were observed in 31.25% of the patients, and chronic osteoarthropathy was observed in four. One patient underwent amputation of index and ring fingers and resection of the first and third metatarsal heads to treat osteomyelitis. One patient underwent balloon angioplasty and stenting for advanced atherosclerotic stenosis of blood vessels of the lower extremities. Conclusions. Euglycaemia and recovery of renal function 6?48 months after SPK resulted in a significant decrease in diabetic complications without clinical signs of regression in some patients. However, some patients suffered progression of complications, reflecting their multifactorial causes. These findings highlight the need for timely diagnosis, treatment and long-term follow up to improve the quality of life and prognosis in patients with T1DM receiving SPK.

This review presents an analysis of clinical and experimental studies related to post-transplantation diabetes mellitus (PTDM) ? a specific complication after solid organ transplantation. A search of the databases eLibrary, PubMed and Scopus using the keywords ?posttransplantation diabetes mellitus?, ?new onset diabetes after transplantation?, ?transplantation? and ?immunosuppression? yielded in 523 results, including four from Russian literature (one original research manuscript). The analysis included original research, reviews, meta-analyses and monographs published not before 2005 in Russian and English. A total of 60 relevant original researches and reviews were included in this review. Diagnostic criteria, disease risk factors and potential pathogenic mechanisms were all considered. The mechanisms of the diabetogenic effect of modern immunosuppressive drugs were analysed. The principles of pre- and post-transplantation screening for PTDM and optimal management strategies for patients with PTDM are presented. The current controversial issues concerning the various aspects of PTDM are discussed.

Objective. Glucose-dependent insulinotropic polypeptide (GIP) as well as glucagon-like peptide-1 (GLP-1) is intestinal incretin hormone that stimulates insulin secretion in response to feeding. Much evidence of GIP contribution to obesity development has been found recently.Aim. The aim of the study was to evaluate glucose-stimulated GIP and GLP-1 secretion in people with type 2 diabetes (T2D) risk factors and different body mass index (BMI).Materials and methods. Total GIP and GLP-1 secretion was estimated in 127 patients with T2D risk factors during OGTT (75 g glucose) on 0, 30 and 120 minutes.Results. Patients with BMI≥ 35 kg/m2 had significantly higher fasting and stimulated GIP levels than participants with less BMI. GIP secretion was also higher in patients was insulinresistance, estimated by HOMA-IR, comparing to non-insulinresistant patients. Difference in GLP-1 secretion in patients within several BMI groups was nonsignificant.Conclusion. Our results suggest GIP is related to obesity degree, that means it can play a role in lipid metabolism and obesity development.

The current update of the consensus algorithm of initiation and intensification of the antihyperglicemic therapy in treatment of the patients with type 2 diabetes mellitus (2015) is based on the preliminary document issued by the Russian Association of the Endocrinologists in 2011. The update was needed due to new data on the safety of the traditional therapeutic options, availability of the new class of the antidiabetic medications, and necessity to add chapter about initiation and intensification of the insulin therapy. The patient-centered approach remains the absolute priority at any stage of diabetes care as it ensures the efficacy and safety of antihyperglycaemic treatment.

Yalkin Halmatovich Turakulov is an internationally known medical researcher whose name is firmly engrained into the history of national endocrinology. He headed the Pharmaceutical Medical Institute, Tashkent Medical Institute, Regional Institute of Medicine, Institute of Nuclear Physics of Uzbekistan Academy of Sciences, Institute of Biochemistry and others institutions various times and was involved in the establishment of many of them. He was a teacher to many doctors and scientists. This article presents his biography and describes his impact on national and world science.

We are glad to present the 7th Edition of Standards of Diabetes Care.These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2012, 2015), American Association of Clinical Endocrinologists (AACE, 2013), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014) and Russian Association of Endocrinologists (RAE, 2011, 2012).Current edition of the ?Standards? also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM increased during the last decade more than two-fold, reaching some 387 million patients by the end of 2014. According to the current estimation by the International Diabetes Federation, 592 million patients will be suffering from DM by 2035. These observations resulted in the UN Resolution 61/225 passed on 20.12.2006 that encouraged all Member States "to develop national policies for the prevention, treatment and care of diabetes".Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian State Diabetes Register, there are at least 4.1 million patients with DM in this country. However, the epidemiological survey conducted by the Federal Endocrinology Research Centre during 2002-2010 suggests that actual prevalence is 3 to 4 times greater than the officially recognized and, by this estimate, amounts to 9-10 million persons, comprising 7% of the national population.Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.Current edition of the "Standards" emphasizes the patient-oriented approach in making decisions on therapeutic goals, such as levels of glycaemia and blood pressure. It also features updated guidelines on the management of vascular complications.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists and diabetologists, primary care physicians, cardiologists and other medical professionals involved in prevention and treatment of diabetes mellitus.

According to the International Diabetes Federation, 10.9 million people have diabetes mellitus (DM) in Russia; however, only up to 4 million are registered. In addition, 11.9 million people have impaired glucose tolerance and impaired fasting glucose levels [1]. One of the significant risk factors for type 2 DM (T2DM) is obesity, which increases insulin resistance (IR). IR is the major pathogenetic link to T2DM. According to current concepts, there are three types of adipose tissue: white adipose tissue (WAT), brown adipose tissue (BAT) and ?beige?, of which the last two types have a thermogenic function. Some research results have revealed the main stages in the development of adipocytes; however, there is no general consensus regarding the development of ?beige? adipocytes. Furthermore, the biology of BAT and ?beige? adipose tissue is currently being intensively investigated, and some key transcription factors, signalling pathways and hormones that promote the development and activation of these tissues have been identified. The most discussed hormones are irisin and fibroblast growth factor 21, which have established positive effects on BAT and ?beige? adipose tissue with regard to carbohydrate, lipid and energy metabolism. The primary imaging techniques used to investigate BAT are PET-CT with 18F-fluorodeoxyglucose and magnetic resonance spectroscopy. With respect to the current obesity epidemic and associated diseases, including T2DM, there is a growing interest in investigating adipogenesis and the possibility of altering this process. BAT and ?beige? adipose tissue may be targets for developing drugs directed against obesity and T2DM.

Achievement of glycemic control is the major therapeutic aim to prevent or delay the onset and progression of diabetes related complications. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. The aim for insulin therapy is to mimic the physiological profile of insulin secretion seen in nondiabetic patients. Development of the insulin analogs has offered new opportunities in the diabetes management to achieve greater safety and tolerability of diabetes treatment. Insulin degludec/insulin aspart(IDegAsp) (Ryzodeg?, Novo Nordisk, Denmark) is the first soluble co-formulation of 70% ultra-long acting insulin degludec and 30% rapid-acting prandial insulin aspart, providing both basal insulin coverage and a prandial insulin bolus in a single injection. This review discusses data regarding the efficacy, safety, tolerability and clinical benefits of IDegAsp. According to the clinical development program IDegAspprovides an achievement of similar glycemic control with superiority in lowering FPG with using less number of injections and lower daily insulin dose, and also associated with numerically lower rates of confirmed and nocturnal confirmed hypoglycaemia in comparison with premixed or basal insulin analogues, as well as a basal component for basal?bolus therapy with supplementary mealtime insulin aspart.Trial results suggest that IDegAspQD or BID maybe an appropriate and reasonable option for initiating insulin therapy in type 1 and type 2 diabetic patients inadequately controlled on maximal doses of oral antidiabetic drugs,and also a simple alternative to basal?bolus treatment in patients who require intensification of insulin therapy, especially when adherence to more complex regimens is challenging.

Genetic susceptibility plays an important role in the risk of developing chronic complications in patients with type 2 diabetes mellitus (T2DM). Aims. In this study, we evaluated the possible association of the polymorphic variants that encode key renal damage mediators (endothelial dysfunction, lipid metabolism and insulin secretion/sensitivity) with the risk of chronic kidney disease (CKD) in patients with T2DM. Materials and Methods. We enrolled 435 patients with T2DM using case-control study design. In 253 patients, we used non-overlapping criteria to form groups with/without CKD (defined as GFR=10 years) (n=75 and 178, respectively) and analysed the following 4 polymorphic markers: I/D in ACE, ecNOS4a/4b in NOS3, I/D in APOB and e2/e3/e4 in APOE genes. We then divided 182 patients in groups with/without CKD (n=38 and 144, respectively) regardless of the duration of diabetes and studied pro12ala in PPARG2, rs5219 in KCNJ11, rs12255372 in TCF7L2 and rs13266634 in SLC30A8 genes. 2 test, and data were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Values of p

Aim. To study the relationship between changes in the artery structure and function and peripheral lymphocyte telomere length in patients with type 2 diabetes mellitus (DM2). Materials and methods. A total of 50 patients with T2DM and without clinical manifestations of cardiovascular disease (CVD) were included in the study; the control group consisted of 49 people. The following tests were conducted for all study participants: carbohydrate metabolism evaluation, carotid artery duplex scan to measure intima?media complex thickness (IMT) and to determine the presence of atherosclerotic plaques, carotid?femoral pulse wave velocity (PWV) measurement and lymphocyte telomere length measurement. Results. The vascular changes were more pronounced in patients with T2DM than in controls. The telomeres were shorter in patients with T2DM than in those without diabetes (9.53?0.1 vs 9.86?0.1, p=0.033). The participants were divided according to the telomere length. Among patients with T2DM, there were significant differences in the condition of the vascular wall [PWV: 10.58?0.1 m/s in patients with ?long? telomeres and 15.08?1.3 m/s in patients with ?short? telomeres; IMT: 0.80?0.09 mm in patients with ?long? telomeres and 0.87?0.05 mm in patients with ?short? telomeres (p=0.024)]. There were no significant differences in the arterial structure between the patient and control groups with ?long? telomeres [PWV: 10.58?0.1 m/s vs 10.5?0.5 m/s (p=0.913); IMT: 0.080?0.09 mm vs 0.73?0.03 mm (p=0.12). However, there were significant differences in the vascular wall condition between the patient and control groups with ?short? telomeres [PWV: 15.08?1.3 m/s vs, 10.7?0.5 m/s (p=0.015); IMT: 0.87?0.1 vs 0.78?0.1 (p=0.03)]. Conclusions. The signs of vascular ageing were more pronounced in patients with T2DM than in controls. However, despite diabetes, vascular changes were minimal in patients with ?long? lymphocyte telomeres, comparable with the state of the vascular walls in healthy individuals. Thus, enhanced lymphocyte telomere length may have a protective effect on the vascular wall and may prevent damage from carbohydrate metabolism disorders.

The mechanisms of podocyte injury and their correlation with metabolic and haemodynamic disorders in diabetes mellitus are considered in detail; the results of the last experimental and clinical studies on this problem are presented in this review. Authors shined the biomarkers, reflecting expressiveness of podocytopathy and structural and functional glomerular changes at diabetic nephropathy. Modern possibilities of treatment for their correction to prevent diabetic nephropathy progression are discussed.

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.

During 2007-2012 years the ?Diabetes mellitus? sub-programme reached the performance targets with the following results. Development of the State Diabetes Register covering all regions of the Russian Federation. The Register facilitates the continuous evaluation and planning of diabetes care in this country, analysis of epidemiological dynamics (including incidence and mortality in diabetes population) and human resources management.Alteration of the demographics of the national diabetes population, specifically: - an increase in life expectancy among T1DM patients: up to 56.7 years (+3.8 years) in males and up to 60.8 years (+4.1 years) in females; an increase in life expectancy among T2DM patients: up to 72.4 years (+3.2 years) in males and up to 74.5 years (+2.9 years) in females; - a reduction in mortality of diabetes patients for 28.4%; Introduction of novel technologies for diagnostics, prevention and management of DM and its complications, that, in turn, allowed to: - decrease the incidence of diabetic nephropathy for 16.1% and extend the pre-dialysis period; - decrease the incidence of diabetic retinopathy for 11.4% and preserve vision in 86-91% patients who still develop this complication; - decrease the frequency of upper- and lower-level amputations for 24% and 28%, respectively, and to reduce the ulcer healing times 2.5 to 3-fold;Introduction of safe and highly efficient human recombinant insulin and its analogues in the regions of the Russian Federation, along with modern methods of insulin administration and outpatient blood glucose monitoring.Establishment of diabetes educational centres (more than 1100 in the regions of the Russian Federation) that resulted in substantial reduction of number and frequency of diabetes-associated hospital admissions.The sub-programme is estimated to have saved 6 727 596.9 thousand Russian rubles of the budgetary funds due to decrease in the incidence of microvascular complications. A total of 360 papers (including 35 in international medical journals), as well as 81 clinical guidance manuals and 23 monographs were published during the course of this sub-programme.

AIM: Combination of cardiovascular and renal disease is currently viewed as a unified cardiorenal syndrome (CRS). The aim of our study was to assess the CRS prevalence and risk factors associated with left ventricular hypertrophy (LVH) in patients with pre-dialysis stages of chronic kidney disease (CKD) of various etiology. MATERIALS AND METHODS: We enrolled 172 patients with CKD to participate in this study. First group consisted of 83 patients with nondiabetic CKD at 2nd through 4th stage (mean age 46-15 years, 51% male and 29% female). Mean glomerular filtration rate (GFR) was 37.2 ml/min (33.9-41.4 with 95% CI); creatinine plasma clearance was 2.9 mg/dl (2.6-3.2). Second group consisted of 89 patients with type 2 diabetes mellitus (T2DM) and CKD at 1st?2nd stage (40% male and 60% female) with albuminuria (mean age 57.3-7.1 years). Duration of diabetes in this sampling was 10.4-7.1 years. All patients underwent standard clinical examination, supplemented with echocardiography to evaluate the influence of general and CKD-related risk factors for LVH. RESULTS: LVH was diagnosed in 37.3% of non-diabetic patients with CKD at 2nd through 4th stage. Aside from classic cardiovascular risk factors (including age, gender, arterial hypertension, family history of cardiovascular diseases, hypercholesterolemia), we observed the impact of kidney-related factors (anemia, plasma creatinine, disturbance of calcium-phosphorus metabolism). CKD progression was associated with elevation in the incidence of concentric and eccentric LVH). Patients with T2DM were diagnosed with LVH in 36% of cases. Increased myocardial mass correlated with plasma levels of uric acid, HbA1c, obesity and albuminuria. There was also a firm association between diabetic nephropathy, left ventricular myocardial remodelling and a history of cardiovascular events. CONCLUSION: In patients with diabetes mellitus and CKD cardiorenal syndrome develops at pre-dialysis stages due to both classic and kidney-related cardiovascular risk factors.

For the past several years, a number of studies addressed glucagon and its role in glycemic homeostasis and the development of diabetes mellitus. Current review discusses basic developmental stages of pancreatic islets with special regard for the role of beta-cells and basic mechanisms of glucagon function. We also highlight promising approaches to diabetes compensation based on adjustment of glucagon secretion.

Expansion of diabetic population (predominantly due to type 2 diabetes mellitus) with chronic kidney disease (CKD) comorbidity constitutes one of the major challenges in modern medicine.Throughout the course of diabetes nephropathy development, from its debut to the terminal stage, survival rate and quality of life are lower than those of other categories of patients. This indicates crucial role of hyperglycemia in accelerated metabolic degradation typical of CKD.Renal disease severely narrows the spectrum of available glucose-lowering agents. Concurrent treatment for hypertension and dyslipidemia, as well as anti-platelet therapy and stimulation of erythropoiesis becomes a complex issue. A creative and patient-oriented approach with clear metabolic and cardiovascular goals should be instrumental in its solution.

AIM: To evaluate the plasma level of circulating heptocyte growth factor (HGF) in patients with comorbidity of post-infarction chronic heart failure (CHF), type 2 diabetes mellitus (T2DM) and obesity. We also aimed to assess possible correlations between HGF levels and parameters of carbohydrate and lipid metabolism, as well as myocardial functional characteristics and classic biochemical severity markers for CHF.17Сахар ный диабет КардиологияСахарный диабет. 2013;(2):17-25 MATERIALS AND METHODS: We enrolled 100 patients for participation in this study, including the following subgroups: 20 individuals with- out cardiovascular and glycemic disorders, 30 patients with CHF, 25 patients with CHF/T2DM comorbidity and 25 diabetic patients with no signs of heart failure. Quantitative plasma HGF analysis was performed with enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma HGF was elevated both in patients with CHF and T2DM as measured against healthy control group. The elevation was most prominent in patients with CHF/T2DM comorbidity and was found to correlate with HbA1c level (r=0.52, p=0.03). Plasma HGF also correlated with BMI (r=0.42, p=0007) in a unified study group, though we observed no statistically significant difference between subgroups with a trend toward higher HGF in obese patients with CHF/T2DM comorbidity (626.1?254.1 pg/ml vs 742.0?210.7 pg/ml respectively; p >0.05). Interestingly, plasma HGF was also significantly higher in controls with BMI >30 km/m2 (324.1?107.7 pg/ml vs 436.9?112.3 pg/ml, p=0.03).Circulating HGF correlated with plasma levels of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and such structural and functional myocardial characteristics as left atrial size and maximum volume along with left ventricular ejection fraction (EF), end-diastolic volume (EDV) and end-diastolic dimension (EDD). CONCLUSION: These findings suggest that HGF may potentially serve as a prediction marker for unfavorable myocardial remodeling and poor prognosis in CHF patients with T2DM and obesity, though this possibility should be further investigated in follow-up studies.

DCCT (Diabetes Control and Complications Trial) study established that intensified insulin therapy in multiple daily injections (MDI) or continuous insulin infusion (CSII) regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM) as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus?) and glulisine (Apidra?) insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

Dear Colleagues!. We are glad to present the 6th Edition of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011), International Diabetes Federation (IDF, 2011), American Diabetes Association (ADA, 2013), American Association of Clinical Endocrinologists (AACE, 2009), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2009) and Russian Association of Endocrinologists (RAE, 2011, 2012). Current edition of the ?Standards? also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM increased during the last decade more than two-fold, reaching some 371 million patients by 2013. According to the current estimation by the International Diabetes Federation, every tenth inhabitant of the planet will be suffering from DM by 2030. These observations resulted in the UN Resolution 61/225 passed on 20.12.2006 that encouraged all Member States ?to develop national policies for the prevention, treatment and care of diabetes?. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian State Diabetes Register, there are at least 3.799 million patients with DM in this country. However, the epidemiological survey conducted by the Federal Endocrinology Research Centre during 2002-2010 suggests that actual prevalence is 3 to 4 times greater than the officially recognized and, by this estimate, amounts to 9-10 million persons, comprising 7% of the national population. . Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. . Current edition of the ?Standards? emphasizes the patient-oriented approach in making decisions on therapeutic goals, such as levels of glycaemia and blood pressure. It also features updated guidelines on the management of vascular complications and new RAE position statement on gestational diabetes, produced in collaboration with Russian Association of Obstetrics and Gynecology. . This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists and diabetologists, primary care physicians, cardiologists and other medical professionals involved in prevention and treatment of diabetes mellitus.

Coordination Council has denoted the importance of adherence to Russian and international guidelines and prominent role of insulin therapy in management of type 2 diabetes mellitus (T2DM). Insulin therapy in T2DM preserves endogenous insulin secretion, prevents or decelerates development of microvascular complications and is known to be the most effective glucose-lowering treatment.

Modern insulin analogues allow safe improvement of glycemic control (not accompanied with increase in body mass or rate of severe hypoglycemic events) and its efficient maintenance during long period of time. In this paper we present results of multicenter 52-week prospective observational study A1chive (Russian cohort, n=9342), designed to assess safety and efficacy of treatment with human insulin analogues (Levemir?, NovoMix? 30 and NovoRapid? (Novo Nordisk) in daily management of insulin naive patients with type 2 diabetes mellitus. Prescription of human insulin analogues resulted in clinically and statistically significant improvement of glycemic control irrespective of initial insulin regimen. Therapy by various regimens (Levemir?, NovoMix? 30 or Levemir? + NovoRapid?) under conditions of daily clinical practice leads to marked improvement in glycemic control as measured by HbA1c (-2.9% in 12 month) with no evidence for negative influence on tolerability and short-term safety of the treatment. Furthermore, decrease in HbA1c levels was associated with pronounced and stable decrease in fasting and postprandial glucose levels (-5.0 mmol/L and -5.7 mmol/L, respectively). By the end of the follow-up all regimen groups reported improvement of QoL by treatment satisfaction criterion.

Cardiovascular complications, a major cause for disability and morbidity in diabetes mellitus (DM), constitute the greatest threat of the diabetes epidemic. Glycemic stability within the therapeutic targets is a prerequisite to prevention of micro- and macrovascular complications of DM. Traditional therapies are aimed at cardinal defects determining development of type 2 diabetes mellitus (T2DM). Unfortunately even in combination they fail to deliver long-term glycemic control without stimulation of weight gain and increase in hypoglycemic risks with negative cardial, renal and hepatic impact. Preservation of beta-cell secretion capacity is also hardly attainable. Incretin-based therapy is a novel, actively developed approach that influences gut hormone physiology for better glycemic control. So far research efforts have yielded two classes of drugs: GLP-1 mimetics and DPP-4 inhibitors. Both are regarded nowadays for a number of important benefits, including beta-cell function improvement, adjusted to human physiology (i.e. stimulation of insulin secretion ?as needed? by the body, - hence low hypoglycemic risk). They also feature positive cardiovascular and body weight effects, thereby taking an important position in complex DM treatment.

Aims. To assess the development of medical care and pharmacological treatment at Endocrine Research Centre (ERC), Moscow, forthe period of 2010-2011 years.Materials and Methods. We analyzed files of 100 patients with type 2 diabetes mellitus (T2DM), who underwent hospitalization to ERCafter January 1, 2010. Key parameters were assessed by means of a study chart, applied for every patient file. Mean values, medians,fractions and confidence intervals (CI) were calculated for studied parameters. Various methods of parametric and non-parametricstatistics were used for comparison of acquired values. Results. Files of 100 patients with T2DM, hospitalized to Endocrinology Research Centre, were analyzed to obtain clinical characteristicsand evaluate initial (prior to hospitalization) and optimized (after hospitalization) therapeutic schemes, as well as spendingpatterns. Mean patient age exceeded 63 years, mean duration period of T2DM was greater than 14.4 years. 86% of patients weredecompensated for glycemic metabolism. 8% were diagnosed with less than 3 diabetes complications, 66% were found to have from 3to 6 complications. Almost all studied cases (98%) featured elevated blood pressure, 63% - diabetic retinopathy on different stages,59% - IHD, 51% - cataract, 49% - CKD. Lower limb angiopathy was found in 30% of cases, diabetic foot syndrome - in 15%.2 patients lost their vision due to diabetic complications and 3 patients experienced lower limb amputation. Arterial hypertension wascompensated in 14 cases from total of 98.Correction of therapy decreased fraction of patients on oral hypoglycemic agents and intermediate acting insulin (NPH), while prescriptionfrequency of short acting insulin and rapid acting human insulin analogues (as well as long acting analogues) showed oppositetrend. Optimization of therapy also included prescription of hypolipidemic drugs for majority of patients, as well as various agents forcorrection of coagulation abnormalities, treatment for CVD and other complications of T2DM.Due to described measures cost of per day treatment for 100 patients increased 2.28 times: from 8 982 RUB to 20 440 RUB (averagecost per day increased from 89.8 RUB to 204.1 RUB).Following the correction, fraction of patients with fasting glycemia 9.0 mmol/l dropped from 37% to 9%, and that with postprandial glycemia >10.0 mmol/l - from 27% to 1%.Mean fasting glycemia level decreased from 8.6 mmol/l to 6.8 mmol/l.Conducted analysis shows that prime expenditures (more that 36% from total cost structure) were associated with hospital stay (includingintensive care unit). Conclusion. Considering expanding nature of DM epidemic, there is an urgent need for effective healthcare management and preventionof severe cardiovascular complications. Priority should be established on balancing efficiency of hypoglycemic agents with theirsafety for short- and long-term prognosis.

The program of renoprotection in patients with diabetes mellitus (DM) is based on a conceptual model of development and progressionof diabetic kidney disease, which is the result of combined impact of genetically modulated metabolic and hemodynamic factors. Compensationof carbohydrate metabolism, which is crucial at the clinical debut of nephropathy, becomes problematic at the late stages ofchronic kidney disease (CKD). ADA (American Diabetes Association) and EASD (European Association for the Study of Diabetes)recommendations formalized in a consensus on the treatment of patients with type 2 diabetes (T2D) should only be extrapolated topatients with CKD with great prudence. Incretin-based drugs gain reputation as promising and perspective therapy for metabolic controlin patients with type 2 DM and CKD. There is an obvious need for large-scale, long-term studies involving patients with various severityof renal disease and related complications to assess the potential of this new diabetes therapy trend.

We discuss results of ORIGIN, a multicenter parallel groups study for efficiency assessment of insulin glargin against polyunsaturatedomega-3 fatty acids or placebo regarding cardiovascular and/or mortality risk reduction in patients with impaired fasting glycemia,impaired glucose tolerance or type 2 diabetes mellitus (T2DM) on its early stage and high risk for cardiovascular events. 12 537 patientstook part in this study; 6 264 were randomized in insulin glargin group, where dosage was adjusted for complete compensationof fasting glycemia (5.3 mmol/l was set as a therapeutic goal). After treatment with glargin therapeutic goal was achieved and furthermaintained for 6.2 years of follow-up. Compensation of fasting glycemia did not affect the outcome of cardiovascular diseases in patientswith early stages of dysglycemia according to primary endpoints. It was not associated with increase in general morbidity and inrisk of hypoglycemic events. Treatment with insulin glargin delayed progression from prediabetes to clinical onset for 28% (OR 0.72,CI 95% 0.58-0.91; p = 0,006), while lowering incidence of DM. Longtime treatment with insulin glargin does not increase incidenceof malignant tumors of different localization, including patients with prediabetes. Due to results of ORIGIN, insulin glargin (Lantus?)has become the most studied human insulin analogue to date.

Prevalence rate of diabetes mellitus worldwide and in Russian Federation is epidemic in its nature. Prospective studies have shown thatmaintenance of glycemic target reduces risk of late vascular complications. In turn, strict glycemic control requires modern approach tointensification of glucose lowering therapy. Randomized clinical trials prove capacity of modern insulin analogues to improve glycemiccontrol while decreasing risk of hypoglycemic events and weight gain. Current paper presents initial data on 9342 patients, participatedin multicenter prospective 52-week observational study A1chieve, conducted in order to assess efficiency and safety of treatment withinsulin analogues Levemir?, NovoMix? and NovoRapid? (Novo Nordisk) in daily management of patients with type 2 diabetes mellitus,who never received that treatment before.

This review presents a comprehensive analysis of actual ambulatory care in patients with type 2 diabetes mellitus provided in 10 federal subjects withinthe period of 1 year. The analysis is based on results from non-interventional open label prospective observational study DIA-CONTROL, whichincluded 9844 patients with DM type 2. The study was aimed to assess the initial level of glycated hemoglobin and its further dynamics according tomeasurements repeated every 3 months. Composition and efficiency of hypoglycemic therapy were also estimated in these patients.Inclusion visit showed 38.5% of patients to have adequate HbA1c levels (8%, which is quite disturbing and suggests a more careful approach to instruction of healthcarespecialists.

Current consensus proposes a differentiated algorithm of initiation and intensification of antihyperglycaemic therapy in treatment patients withtype 2 diabetes mellitus. Patient-centered approach is considered a priority at any stage of diabetes care, as it ensures efficiency and safety of treatment.This document formulates guidelines for setting adequate therapeutic goals depending on vascular complications, age, life expectancy and riskof hypoglycemic events. Therapeutic options are stratified with regard to initial HbA1c level. This Algorithm considers all classes of antidiabetic medicationsregistered in Russian Federation, rational and irrational combinations of drugs as well as contraindications.

Some chronic systemic diseases, including diabetes mellitus, require the life-long use of biotechnological medical products, of which quality,effectiveness and safety depends the duration and quality of life for patients.Patent protection expiry of many original biological agents has assumed the key role in development of biosimilars (replica versions of originalbiotechnological products) and their broad entrance to the pharmaceutical market. Because of structural complexity of biological products andimpossibility of precise reproduction of patented processing, biosimilars are not ideal duplicates of original substances. Despite numerous evidence oftherapeutic nonequivalence, danger of mechanical substitution of original agents still exists in Russia due to lower price of biosimilars - and lackof legislative acts, regulating registration and circulation of such drugs.In this article we characterize biosimilars in great detail and review major problems of their use, that is: aspects of quality control; disparity withoriginal bio-agents in efficacy and safety; clinical trial requirements, registration procedures and subsequent safety control.

The review addresses the questions of history, clinical features and outcomes of simultaneous pancreas-kidney transplantation in patients with diabetesmellitus type 1. This approach was shown to have positive aspects, such as improvement of glycemic control, rapid normalization and long-termmaintenance of glycated hemoglobin levels, disappearance of hypoglycemic events, and deceleration of coronary artery disease progression resultedin reduced incidence of cardiovascular mortality. Operative risk and post-transplantation complications are also described in details.

Aim. To study effect of concomitant type 2 diabetes mellitus on the number of circulating progenitor cells (CPC) in patients with coronary heart disease(CHD) and postinfarction heart failure (ischemic cardiomyopathy).Methods. The number of CPC (CD34+ cells) was determined by flow cytophotometry in 47 patients with CHD including 14 with CHD + DM2; 12patients without CHD and DM2 made up the control grouP. Enzyme-linked immunosorbent assay was used to measure N-terminal precursor of brainnatriuretic peptide (NT-proBNP), immunoreactive insulin (IRI) and C-peptide levels. Results. The number of CPC in patients with ischemic cardiomyopathy without DM2 was 33.4% greater than in controls. In patients with cardiomyopathyand DM2 the number of CPC depended on the quality of diabetes compensation. It was lowest in case of decompensated DM2 (HbA1c=9.5?1.8%).In patients with compensated/subcompensated DM2 (HbA1c=6.8?0.3%) it was significantly higher than in controls and patients with ischemiccardiomyopathy without DM2 (mean 46.5 (p=0.006) and 40.0% (p=0.02) respectively). Conclusion. The number of CPC in peripheral blood of patients with ischemic cardiomyopathy and DM2 correlated with the level of DM compensation.It was lowest in patients with decompensated DM2 and exceeded the normal number in patients with CHD without DM2. The number of CPC inverselycorrelated with blood glucose level. Positive correlation of CPC number with IRI and C-peptide levels was documented in control subjects and patientswith CHD without DM2.

The safety of antidiabetic medications has received much attention in the resent past. Although concerns on the safety of glibenclamide therapy iscontroversial, some studies showed an increased risk of cardiovascular morbidity (f.e. myocardial infarction) and risk of mortality in subjects usingglibenclamide, but not other SU (gliclazide or glimepiride)

Сахарный диабет (СД) ? системное заболевание обмена веществ, которое приняло пандемический характер распространения, что побудило Организацию Объединенных Наций (ООН) в декабре 2006 г. принять резолюцию, призывающую ?создавать национальные программы по предупреждению, лечению и профилактике СД и его осложнений и включать их в состав государственных программ по здравоохранению?. За последние 30 лет по темпам прироста заболеваемости СД опередил такие инфекционные заболевания, как туберкулез и ВИЧ. Численность больных СД в мире за эти годы выросла более чем в 2 раза и достигла к 2011г. 366 млн человек. В Российской Федерации, как и во всех странах мира, отмечаются высокие темпы роста заболеваемости СД. По данным Государственного регистра больных СД на январь 2011 г. в РФ по обращаемости в лечебные учреждения насчитывается 3,357 млн больных СД. Между тем результаты контрольно-эпидемиологических исследований, проведенных ФГБУ Эндокринологический научный центр (ЭНЦ) в период с 2002 по 2010 г., показали, что приблизительно еще 6 млн россиян имеют СД, но не знают об этом и, следовательно, не получают лечения. Самыми опасными последствиями глобальной эпидемии СД являются его системные сосудистые осложнения ? нефропатия, ретинопатия, поражение магистральных сосудов сердца, головного мозга, периферических сосудов нижних конечностей. Именно эти осложнения являются основной причиной инвалидизации и смертности больных СД. В РФ с 1996 г. осуществляется Федеральная целевая программа (ФЦП) ?Сахарный диабет? (с 2002 г. ? подпрограмма ФЦП ?Предупреждение и борьба с социально значимыми заболеваниями?), в рамках которой создана современная диабетологическая служба, позволившая осуществить реальный прорыв в диагностике, лечении, профилактике СД и его осложнений на территории РФ на основе внедрения современных диагностических систем, эффективных и безопасных лекарственных препаратов и средств самоконтроля, высокотехнологичных методов лечения сосудистых осложнений. Данное руководство ? ?Алгоритмы специализированной медицинской помощи больным сахарным диабетом? ? является пятым, обновленным и дополненным изданием. Руководство базируется на международном и отечественном опыте лечения СД, включая рекомендации Международной Диабетической Федерации (IDF 2005), Американской Диабетической Ассоциации (АDA 2011), Американской Ассоциации клинических эндокринологов (AACE, 2009), Международного общества по детскому и подростковому диабету (ISPAD, 2009), Российской ассоциации эндокринологов (РАЭ, 2011), а также результатах завершенных международных (ADVANCE, ACCORD, VADT, UKPDS и др.) и отечественных рандомизированных клинических испытаний у больных СД, в которых участвовали многие российские клиники. В новом издании Алгоритмов нашли отражение изменения, касающиеся диагностики СД, формулировки диагноза при СД, индивидуализации целевых значений гликемического контроля при СД 1 и 2 типа, стратегии сахароснижающей терапии при СД 2 типа, внесены уточнения по диагностике и лечению осложнений СД. Целью данного руководства является стандартизация и оптимизация оказания медицинской помощи больным СД во всех регионах России на основе доказательной медицины. Проект данного руководства неоднократно обсуждался на общероссийских конгрессах и форумах и получил одобрение абсолютного большинства специалистов. Рекомендации предназначены для эндокринологов и диабетологов, терапевтов, кардиологов, а также всех специалистов, принимающих участие в лечении больных СД.