Search

Objective: The aim of the study was to assess the effectiveness and safety of long-term sibutramine therapy in routine clinical practice. Methods: In total, 98,774 patients (82.3% women, 17.7% men) from 142 cities of the Russian Federation were enrolled in the PRIMAVERA program. The mean age of the patients was 39.39 ± 10.38 years, the mean body weight was 99.1 ± 14.28 kg, and the mean BMI was 35.7 ± 4.41 kg/m2. The duration of the sibutramine therapy was determined by physicians: 59.3% of patients took the drug for 6 months, the treatment course of 37.7% of patients was 12 months, and 3% of patients had treatment for 3 months. Results: The BMI reduction correlated with the treatment duration: 3.4 ± 1.53 kg/m2 after 3 months of therapy, 5.4 ± 2.22 kg/m2 after 6 months, and 7.2 ± 3.07 kg/m2 after 12 months. The body weight reduction after 3, 6 and 12 months of treatment was 9.5%, 15.1%, and 19.7%, respectively. The body weight loss associated with sibutramine treatment was accompanied by a slight decrease in blood pressure and did not lead to any significant increases of the heart rate. Conclusions: The results of the PRIMAVERA study confirmed the lack of increased risk of using sibutramine in routine clinical practice in patients without underlying cardiovascular disease and low rate of adverse events.

Nenets are Samoyedic people belonging to Ural contact minor race, with combined anthropological signs of both Caucasoid and Mongoloid races. In this population, the occurrences of type 1 diabetes mellitus (T1DM) were registered during 30 years. Aim. The study aimed to investigate the incidence of human leucocyte antigen (HLA)-haplotypes in Nenets compared with those in the Russian population. Materials and Methods. HLA-typing was performed in 61 healthy Nenets subjects residing in the Arkhangelsk district, 341 Russian subjects from Moscow and natives from the Vologda district. Results. DRB1*04-DQA1*0301-DQB1*0302 was similar in all the three study populations: 11.5%, 8.5% and 11.6% for Nenets, Moscow and Vologda populations, respectively (p > 0.05). However, the incidence of the second most important high predisposed haplotype DRB1*17(03)-DQA1*0501-DQB1*0202 was significantly lower in Nenets (1.6%) than in the Moscow and Vologda populations (10% and 7.4%, respectively) [(p1.2 = 0.03 (x2 = 4.42); p1.3 = 0.12 (x2 = 2.46)]. The incidence of DRВ1*01-DQA1*0101-DQB1*0501 haplotype specific for both Russian populations was also significantly lower in Nenets (3.3%) than in the Moscow and Vologda populations (11% and 12.4%, respectively) [(p1.2 < 0.05 (x2 = 3.34); p1.3 < 0.05 (x2 = 3.85)]. The incidence of protected haplotypes (DRB1*11-DQA1*0501-DQB1*0301 and DRB1*13-DQA1*0102-DQB1*0602/8/DRB1*13-DQA1*0103-DQB1*0602) was significantly higher in Nenets than in the Moscow and Vologda populations: 32.8% versus 12.5% and 9.1%, respectively [(p1.2 < 0.001 (x2 = 13.48); p1.3 < 0.001 (x2 = 17.3)] and 16.4% versus 8.5% and 11.1%, respectively [(p1.2 = 0.07 (x2 = 3.14); p1.3 = 0.3 (x2 = 0.97)]. The incidence of some neutral haplotypes was also significantly higher in Nenets: haplotype DRB1*12-DQA1*0501-DQB1*0301 was detected in 29.5% of Nenets compared with 2.5% and 1.2% of the Moscow and Vologda populations, respectively [(p1.2 < 0.001 (x2 = 42.43); p1.3 < 0.001 (x2 = 37.66)]; haplotype DRB1*09-DQA1*0301-DQB1*0303 was detected in 14.8% of Nenets compared with 1% and 2.5% of the Moscow and Vologda populations, respectively [(p1.2 < 0.001 (x2 = 21.9); p1.3 < 0.001 (x2 = 10.04)]. Conclusions. According to preliminary evidence, the incidence of predisposed haplotypes was significantly lower and that of protected haplotypes was significantly higher in Nenets than in the Moscow and Vologda populations, which probably play a role in the very low incidence of T1DM in Nenets.

Aim. To study the quantity of endothelial progenitor cells (EPCs) and levels of vascular endothelial growth factor A (VEGF-A) in patients with type 2 diabetes mellitus (T2DM) after endovascular interventions on coronary and peripheral arteries. Materials and methods. We observed 68 patients with stable angina pectoris and critical limb ischaemia, admitted for elective percutaneous coronary intervention and endovascular revascularisation of the lower extremity. The number of CD34+VEGFR2+CD45- and CD34+CD133+CD45- cells and levels of VEGF-A were determined before endovascular intervention and 2–4 days after the surgery. Results. We found that in patients without diabetes, the levels of EPCs increased significantly after endovascular interventions (CD34+VEGFR2+CD45-cells, p < 0.0001; CD34+ CD133+CD45-cells p = 0.041). The levels of EPCs in the peripheral blood of patients with T2DM before and after endovascular interventions did not significantly differ. The analysis of VEGF-A showed a statistically significant increase after intervention in both groups. In addition, in patients with an HbA1c level of 10 years, the levels of EPCs before and after endovascular interventions did not significantly differ. Conclusions. Patients with diabetes exhibited impaired EPC mobilisation after endovascular interventions. Poor glycaemic control and a long duration of diabetes are among the risk factors of EPC mobilisation.

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

The extent of damage to the nervous, vascular and microcirculatory systems in diabetic patients determine the regulation of physiological events that lead to the formation of chronic wounds, reduction of patient quality of life and increase of the financial value of medical care. Successful physiological repair is impossible without the successive phases of inflammation, proliferation and wound healing. Keratinocytes are the major cellular barrier components of the epidermis. These cells play an important role in physiological repair, as suggested by recent research, with many cells able to secrete steroid hormones de novo. Damage to the integrity of the skin leads to keratinocyte activation, triggering a cascade of reactions that contribute to changes in epidermal cell phenotype and lead to their proliferation and migration, analogous to changes in cellular adhesion and configuration of the cytoskeleton. An open question remains as to how the keratinocyte cell cycle, which is altered under conditions of hyperglycemia, and neurotransmitter metabolism during different stages of physiological repair are regulated. Understanding these processes will provide a scientific basis for the development of new targets for pharmacotherapies.

Type 1 diabetes mellitus (T1DM) was used from the viewpoint of human immunogenetics as an example of the most widely studied immunity-mediated disease. This was done in order to develop, approve and implement a new clinical approach to determine immunity-mediated susceptibility or resistance to autoimmune diseases. The approach is based on analysis of entire HLA-DRB1 genotypes (not separate HLA-DRB1 haplotypes) of the study participants. Therefore, more effective and personalised classification of T1DM risk groups was achieved by exclusion from significant contingents.

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.

Basal insulin represents an essential tool in the treatment of both type 1 and type 2 diabetes mellitus. The development of insulin analogues has improved the possibilities of diabetes treatment. Despite significant progress in understanding the physiology, chemistry, kinetics and action of insulin, currently available basal insulin products do not optimally mimic the endogenous profile of insulin. Although basal insulin analogues have some advantages over neutral protamine Hagedorn insulin in diabetes treatment, hypoglycaemia remains the main problem in the achievement of optimal glycaemic control in most patients with diabetes. These unmet clinical needs have stimulated the development of new basal insulin analogues with improved pharmacological profiles. This article reviews the specific characteristics of new long-acting insulin analogues to try and understand their benefits and limitations in the improvement of diabetes management and their possibilities in physiologic and safe insulin replacement.

Aim. To evaluate the renal concentration capacity in patients with mild and severe primary hyperparathyroidism (pHPT).Materials and methods. The study included 77 patients (median age 57 years [52;61]) with pHPT, first group was comprised of patients with mild form (n=23), second group contained patients with severe pHPT without nephrolithiasis (n=28) and the third group contained patients with pHPT and nephrolithiasis (n=26). Osmolality index was calculated as urine osmolality to blood osmolality ratio. Renal concentration capacity impairment was diagnosed with osmolality index less than 2.Results. Osmolality index in patients with pHPT was low with median 1,66 [1,38;2,1]. We found a high prevalence of renal concentration capacity impairment in patients with pHPT, that was 71,4%. Regardless of presence of nephrolithiasis both patients with mild and severe pHPT had similar prevalence (70%, 75% and 69,2% respectively).Conclusions. Renal concentration impairment is common in mild and severe pHPT. The findings of this study necessitate for measurement of urine osmolality or osmolality index in all patients with pHPT.Комбинированную терапию ожирения (диета, физические нагрузки + прием орлистата) в течение 7 ± 1 месяцев получали 15 пациентов первой группы (СОАС), 5 – во второй (инсомния) и 8 пациентов без нарушений сна. При сравнении групп не выявлено статистически значимых различий по числу пациентов, принимающих медикаментозную терапию ожирения (р < 0,05). Через 7 ± 1 месяцев лечения ожирения среднее снижение МТ у больных с синдромом инсомнии составило –2,5 [–4; 0] кг, у больных с СОАС –7 [–18; –2] кг, у пациентов без нарушений сна –6,5 [–12; –2,25] кг.

Recent data suggest that chronic critical limb ischaemia (CLI) is the most important reason for amputation among diabetic patients. The high prevalence of CLI in this patient group is associated with specific clinical and morphological properties of peripheral arterial disease. Percutaneous transluminal angioplasty is an appropriate primary therapy, but it is not considered early in the disease process, and is instead reserved as a limb salvage strategy. Low primary patency, despite optimal clinical effects, remains a typical issue of percutaneous transluminal angioplasty for diabetic patients in particular. Thus, the indications, technical success and clinical results of endovascular revascularisation need to be clarified in patients with diabetes. Although difficult, the procedure can be effective through a multidisciplinary approach.

The prevalence of type 2 diabetes is increasing dramatically, and the pathogenesis of the disease has been studied extensively in recent years. Of particular interest, incretins are reported to cause changes in insulin secretion that affect the natural development of the disease. The emergence of new drugs that act via the incretin axis have led many clinicians to consider their place in clinical practice.

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.

Pharmacoepidemiological research is the first stage of the clinical and economical evaluation of treatment with pharmaceutical agents. It plays an important role in providing reliable information about treatment regimens for patients with type 2 diabetes mellitus (T2DM). The results of the analysis of the utilisation of hypoglycaemic drugs are country specific and are associated with different epidemiological characteristics of the disease, cost of drugs and financing of the healthcare system. Analytical pharmacoeconomic studies allow the evaluation of the rational use of drugs, characteristics of treatment in clinical practice and their conformity to national and international clinical guidelines. Aim. To study the characteristics of treatment with insulin and oral hypoglycaemic drugs in Moscow-based patients with T2DM and to calculate the average cost of hypoglycaemic drugs per person per year. Materials and methods. A retrospective cohort pharmacoepidemiological study was performed by analysing information from the national register of diabetic patients from two administrative districts in Moscow. In total, 48,978 adult patients (older than 18 years) were registered with T2DM between 2000 and 2012. The study of treatment regimens was conducted using the standard international ATC/DDD methodology, and the correlation of fixed dose to appointed daily dose was calculated. The annual average cost of treatment for patients with T2DM, including different hypoglycaemic drugs (insulin and oral hypoglycaemic drugs) in the form of monotherapy and different combinations, was calculated. The average annual cost of hypoglycaemic therapy for patients with T2DM was calculated for the first time in the Russian Federation. Results. The majority of study patients received hypoglycaemic drugs (98.5%), and only 1.5% of the patients diagnosed with T2DM were on dietetic therapy. Of the patients receiving drugs, 90% received oral hypoglycaemic drugs, and 10% received insulin (basal-bolus regimen 4.6%, basal insulin with oral hypoglycaemic drugs 3.8% and ?MIX-insulin? 1.1%). The most frequently prescribed oral hypoglycaemic drugs were derivatives of sulphonyl urea and metformin (87% and 71%, respectively), and 12% of the patients received premixed combinations of these drugs. Other groups of oral hypoglycaemic drugs accounted for only a small proportion of oral hypoglycaemic drugs (approximately 2%) and included glinide (1.8% of the patients), thiazolidinedione (0.4%) and inhibitors of alpha-glucosidase (0.17%). In the group of derivatives of sulphonyl urea, the most frequently prescribed drugs were glibenclamide (46.4%), gliclazide (38.7%) and glimepiride (14%). The average annual treatment cost per patient was 7,467 rubles. Conclusion. The pharmacoeconomic analysis revealed that the treatment of T2DM was insufficiently effective in 48% of the patients (HbA1c>7%). Most patients received monotherapy with metformin or derivatives of sulphonyl urea, among which glibenclamide was the most frequently prescribed drug. The treatment of patients with T2DM in 2011 was characterized by a low frequency of insulin prescription, rare usage of other groups of oral hypoglycaemic drugs (only 2%) and a mismatch between fixed dose and appointed daily dose. The average annual cost of hypoglycaemic drugs per patient with T2DM in 2011 in Moscow was 7,467 rubles.

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.

Introduction: a significant improvement was shown in metabolic control at the early stages after BPD, which was associated with GLP-1 and was regardless of weight loss.Aim: to study the secretion of GLP-1, GIP, insulin and glucagon and their relationship to the parameters of the carbohydrate metabolism among patients with obesity and type 2 diabetes before and 3 months after BPD.Materials and Methods: the check-up involved 22 patients with obesity (BMI 50.1 [41.3; 53.8] kg/m²) and type 2 diabetes. Determined: glucose, HbA1c, insulin, glucagon, GLP-1, GIP.Results: after the surgery for weight loss of 15.8% was showed a reduction of fasting and postprandial glycemia, a reduction of AUCglucose, HbA1c, НОМА-IR and hyperinsulinemia. The secretion of GLP-1 with a peak at 30' (test with a standard breakfast) increased, AUCGLP-1 – to 1.8-fold, the basal secretion of GIP – almost 2-fold and AUCGIP – to 1.7-fold; decreased of a secretion of glucagon with a minimum at 60' and AUCglucagon. A negative correlation was revealed between GIP and glucagon, AUCglucose and AUCglucagon; a positive correlation was revealed between GLP-1 and insulin. The weight loss was accompanied by an inversely proportional increase of GLP-1.Conclusion: More than 90% of the surveyed patients achieved a satisfactory glycemic control as early as 3 months after BPD. The significant improvement of the parameters of the carbohydrate metabolism was associated with elevated levels of GLP-1 and this improvement does not depend of weight loss.

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.

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.

For 40 years, research continues to improve the forecasting methods and the development of effective and safe methods of preventing type 1 diabetes mellitus (T1DM). Аim. Prediction of the early preclinical stage of T1DM. Materials and methods. We studied the predisposing and protective haplotypes (HLA-DRB1, gene DQ) together with immunological markers (ICA, GADA, IAA) in 224 discordant/concordant families. Results. At the Endocrinology Research Centre, population and family risks of the development of T1DM in Russia were calculated on the basis of population genetic approaches. The analysis of the prevalence of HLA genotypes among T1DM patients revealed that the high-risk haplotypes in the structure of genotype(s) DQ2 and/or DQ8 in combination with the others were 78%: of these genotypes DQ2/DQ8, DQ2/DQ2, and DQ8/DQ8 accounted for 35%; DQ2/X* and DQ8/X* accounted for 43%; and the low-risk genotype Х*/Х* accounted for 22%. The genotype Х/Х consisted of weaker predisposing haplotypes that were specific to the Russian population in combination with neutral haplotypes or those consisting of neutral haplotypes only. The analysis of patients with T1DM genotypes revealed that high-risk genotypes (DQ2/DQ8) were more common in ill children up to the age of 5 (33% of cases) than in T1DM children over 10 years (23%) (p=0.05). Conversely, the low-risk genotypes were significantly less likely to be found in children with manifestations of diabetes up to 5 years than in sick people over 10 years [5% and 13%, respectively (p

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.

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.

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.

Aim. To assess the extent of the lower limb arterial calcification and to evaluate the long-term outcomes of percutaneous transluminal balloon angioplasty (PTBA) in patients with diabetes mellitus (DM), critical limb ischemia (CLI) and chronic kidney disease (CKD). Materials and Methods. 94 patients with CLI formed two groups (CKD-positive and CDK-negative). Quantitative assessment of tibial arterial calcification was performed with non-contrast CT. Outcomes of angioplasty were monitored during the 18?6 months of the follow-up period by means of duplex ultrasonography. Results. Long-term outcomes of PTBA were significantly worse in patients with CKD. Nevertheless, limb preservation and survival rates were relatively satisfactory in both groups (74% and 72%, respectively). Conclusion. PTBA in patients with DM, CLI and CKD presents a technical challenge. Despite that, in many cases the endovascular intervention allows avoiding high-level amputations and improves survival rates.

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.

Diabetic foot syndrome (DFS) is one of the most prevalent and financially demanding complications of diabetes mellitus (DM). According to a number of expert analyses, DFS counts for 15% to 25% of total diabetes spendings by the developed economies. The Advanced Medical Care Program in Russian Federation covers expanses for patients with DFS. However, DFS patient profile has no dedicated budgeting quotation as yet, and that of ?general endocrinology? does not meet specific clinical requirements. An expenditure analysis was performed to facilitate the development of budgetary recommendations. The survey included two major steps: a systematic analysis of the data available from periodic literature, followed by an assessment of routine clinical practice in a federal healthcare institution (using the example of Moscow Endocrinology Research Centre).

Diabetes mellitus (DM) dominates the chronic disease pandemics by its exceptionally rapid expansion into communities all over the world. DM is a disorder of complex nature that urges further dedicated studies and ingenuity in the search for novel therapeutic approaches. Nowadays, the blooming development of life sciences gives birth to some prodigious possibilities in treatment, diagnostics and prevention of this disease.

AIM: To determine whether duplex ultrasonography (DU) without verification with diagnostic angiography (DA) is a sufficient visual- ization technique for pre-operative examination of patients with CLI (critical limb ischemia) indication for percutaneous transluminal balloon angioplasty (PTBA). MATERIALS AND METHODS: We examined 254 patients (290 limbs in total) with diabetes mellitus (DM) and CLI. All participants were subdivided into two groups: ?A? (PTBA with pre-operative DU+DA) and ?B? (PTBA with pre-operative DU). We evaluated data coherence between DU and DA (pre- or intraoperative) methods, as well as DU diagnostic specificity and sensitivity in determining degree and localization of vascular lesions. We also investigated specific clinical factors compromising DU diagnostic capabilities in patients with DM. RESULTS: Our data suggests adequate coherence between DU and DA for pre-operative visualization. Group ?B? showed significantly higher diagnostic sensitivity and specificity for visualization of the lower third of superficial femoral artery and tibial arteries despite abdominal obesity, grossly evident calcification and peripheral edema. CONCLUSION: Duplex ultrasound is efficient and precise enough to determine optimal management tactics in most patients with DMand CLI without resort to invasive methods.

Aim. To evaluate the association of rs2476601 and rs2488457 polymorphisms with type 1 diabetes mellitus (T1DM) in several ethnic populations of Russian Federation and to estimate the cross-populational differences of these polymorphisms.Materials and Methods. A case-control design was applied to study the aforementioned polymorphisms in five ethnic populations of Russian Federation: Bashkir, Yakut, Buryat, Udmurt, Russian. We analyzed DNA samples from 491 patients with T1DM and 408 control subjects. Polymorphisms were identified with RFLP-PCR and RT-PCR. Strength of association was evaluated as odds ratio (OR). All calculations were performed with StatSoft STATISTICA (version 6) and Microsoft Excel 2003 software applications.Results. PTPN22 1858Т+ genotypes were associated with T1DM in Udmurt, Russian and Bashkir populations and PTPN22 1123C+ genotype in Buryat population. We did not find any associations of PTPN22 gene polymorphisms with T1DM in Yakut population. Cross-ethnic comparison of polymorphism frequencies showed statistically significant differences. Allele frequency distribution in Buryat population significantly differs from that of other studied ethnic groups with G-1123C (rs2488457; 71.3%) being a significantly more common finding than C type allele. Russian population of Moscow and Moscow Region is also characterized by higher prevalence of Ttype allele (13%) in C1858Т (rs2476601) polymorphism.Conclusion. Ethnic populations of Asian regions of Russian Federation, characterized by lower rates of T1DM (Yakut and Buryat) demonstrated highest prevalence of G-allele in G-1123C (rs2488457) polymorphism. On the contrary, analyses from Russian population of Moscow and Moscow Region, known to have higher rates of T1DM, suggest higher prevalence of T-allele in C1858Т (rs2476601) polymorphism.

Aims. To evaluate transcutaneous oximetry as a method for diagnostics and monitoring in patients with diabetes mellitus (DM) and critical limb ischemia (CLI) after percutaneous transluminal balloon angioplasty (PTBA). Materials and Methods. We enrolled 126 patients with DM and CLI for participation in this study (148 limbs in total). 22 patients underwent PTBA on both lower limbs, and 104 ? on single limb. Transcutaneous oximetry and duplex ultrasonography of lower limb arteries was performed prior to PTBA with subsequent examinations on 5-7th days, 1st, 3rd and 6th month after intervention. Transcu- taneous oxygen tension (TcpO2) was measured by Radiometer (Copenhagen) oximeter system. Duplex ultrasonography was performed on Voluson 730? Expert system (GE Medical Systems Kretztechnik GmbH&Co OHG, Austria). Results. Multiple factor analysis suggests that results of TcpO2 monitoring prior to and after PTBA are influenced by presence of ischemic heart disease, severe lower limb infections, serum creatinine, arterial hypertension and lower limb reperfusion edema. We observed a strong correlation of TcpO2 with the degree of anterior tibial artery and dorsal pedis artery occlusion. Conclusion. Transcutaneous oximetry allows evaluation of CLI severity and efficiency of PTBA in the majority oа patients with DM and CLI. Certain comorbidities impose limitations on this technique. Efficiency of endovascular intervention should be evaluated based on complex non-invasive examination, clinical data and signs of CLI.

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.

Current document presents the expert consensus of Russian Association of Endocrinologists and Russian Society of Obstetrician- Gynecologists on diagnostic criteria of gestational diabetes and other glycemic disorders of pregnancy. The consensus is based on analysis of HAPO (Hyperglycemia and Adverse Pregnancy Outcomes Study) - a major multinational study, that included more than 23000 patients. Project of current consensus was repeatedly discussed during meetings of the research group and publicly addressed at 6th Pan-Russian Congress of Endocrinology with international participation ?Modern Endocrine Technologies?, as well as Pan-Russian Educational Interscience Conference ?Complicated Pregnancy and Preterm Birth?.

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.

Current document presents a coherent viewpoint of Russian Association of Endocrinologists and Russian Association of Obstetriciansand Gynaecologists on diagnostic criteria of gestational diabetes mellitus (GDM) and other glycemic disorders during gestation. Currentapproach is based on analysis of high-profile multinational study HAPO (Hyperglycemia and Adverse Pregnancy Outcomes Study),which included more than 23 000 pregnant women. This project was repeatedly reviewed on workgroup sessions and presented orallyon 6th Russian Congress of Endocrinology with international participation, as well as Russian interdisciplinary educational congressGestational Complications and Premature Delivery.

AIMS: In order to study type 1 diabetes mellitus associations, we conducted a comparative analysis of allele and genotype frequencydistribution of polymorphic markers rs41295061 and rs11594656 of IL2RA gene, which encodes α-chain of interleukin-2 receptor, - and rs2069762, a marker of IL2, gene, encoding interleukin-2. MATERIALS AND METHODS: Experimental group included 451 patients with type 1 diabetes mellitus (DM); control group consistedof 306 healthy subjects (both groups were represented by ethnic Russians). Alleles and polymorphic markers were identified byreal-time amplification method. RESULTS: A comparative analysis of patients with type 1 DM and healthy control group did not show statistically significant differencesfrom the viewpoint of allele and genotype frequency distribution of polymorphic markers rs41295061, rs11594656 and rs2069762. This makes Russian patients considerably different from European ones where markers in question show substantialassociation with type 1 DM. CONCLUSIONS: A comparative analysis of allele and genotype frequency distribution of IL2-RA and IL2 genes polymorphic markersshowed population differences in association of these markers in Russian and European patients.

The article presents a clinical example of integrated surgical management in patient with multifocal atherosclerosis, chronic kidney disease andneuro-ischemic form of diabetic foot syndrome

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.

Aim. To perform cost-effectiveness analysis of prescription of pharmaceutical products and dressing materials and their consumption volume for inandout-patient treatment of diabetic foot syndrome (DFS). To analyse efficacy of the treatment in terms of modern therapeutic standards. Materials and methods. This retrospective study is based on the medical documentation of 139 DM1 and DM2 patients with DFS from differentmedical facilities of Moscow (2007). 72 patients were given general out-patient care by surgeons of city polyclinics, 50 ones received specialized aidin the regional Diabetic Foot Cabinet. 67 patients were hospitalized: 20 for general care in the department of purulent surgery of a military hospital,27 for specialized care in the department of purulent surgery of a city hospital, 20 for high-technology care in the endocrinological clinic of the FirstMoscow State Medical University. Results. Therapeutic strategy for DFS patients used in the regional Diabetic Foot Cabinet met the current therapeutic standards. General out-patientcare by surgeons of city polyclinics was at variance with the algorithms adopted in this country. Pharmacoeconomic analysis of the spectrum of pharmaceuticalproducts used for in- and out-patient treatment of DFS patients revealed frequent and ungrounded application of drugs whose woundhealing effect remains to be confirmed (pentoxifylline, thioctoic and alpha-lipoic acids). Conclusion. Additional training courses for surgeons of Moscow polyclinics are needed to improve the quality of medical aid to DFS patients. Suchpatients must be referred to regional Diabetic Foot Cabinets. Pentoxifylline, thioctoic and alpha-lipoic acids need to be substituted by pharmaceuticalswith validated therapeutic efficacy.

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.

С учетом масштаба развивающейся эпидемии СД существует острейшая необходимость разработки эффективного терапевтического алгоритма сахароснижающего лечения, позволяющего достичь компенсации углеводного обмена и предупредить развитие тяжелых сосудистых осложнений этого заболевания. При этом приоритетом в выборе терапевтических средств должна стать эффективность сахароснижающего действия препаратов при их безопасности для пациентов (как крат- косрочной, так и отдаленной).

The risk of type 1 diabetes mellitus (DM1) depends in the first place on the presence of predetermining HLA DR haplotypes, DQ genes, and specific autoantibodies.Aim. Prospective observation of DM1 risk groups (healthy sibs of DM patients) for the elucidation of the role of genetic and autoimmune abnormalities in thedevelopment of DM1. Materials and methods. Predetermining and protective haplotypes (HLA-DRBI, DQ genes) in combination with immunological markers (autoantibodiesto cytoplasmic structures of betbeta-cells (ICA), anti-insulin autoantibodies (IAA), anti-glutamate decarboxylase autoantibodies (GAD)) were studied in healthysibs of mean age 11.9?5.8 years selected from 143 discordant families of patients with DM1. In addition, a random sample of 599 DM1 patients (mean age7.5?6.2 years) was enrolled for molecular genetic studies (HLA-DRBI-DG genes). The control group comprised 200 subjects. Results. DQAI*0501-DQB1+0201 (DQ2) and DQAI*0301-DQBI*0302 (DG8) haplotype heterozygosity creating the highest risk of DM1, the healthy sibswere divided into 3 risk groups. The high risk group 1 (DQ2/DQ8) included 23 (13.5%) subjects, moderate risk group 2 (DQ2/X, DQ8/X) 85 (59.7%), andlow risk group 3 (X/X; X - any haplotype besides DQ2, DQ8) 63 (36.8%). The frequency of autoantibodies (AB) of 2 or 3 species in group 1 was higher thanin groups 2 and 3 (26.1, 14.1, 11.1% respectively, p>0.05; 8.7, 2.4, 0%, p

По данным Государственного регистра больных сахарным диабетом, на 1 января 2009 года в России сахарный диабет (СД) выявлен более чем у 3 миллионов человек, из них 2,7 миллиона приходится на 2 тип. Последние 15-20 лет интерес к выбору оптимальной терапии на всех этапах развития СД 2 типа возрастает. Это связано с одной стороны с появлением новых научных данных, а с другой стороны со всё увеличивающимися возможностями фармакологического воздействия у этой категории больных. В настоящее время специалисты выделяют 9 групп таблетированных и инъекционных препаратов. Эти данные представлены в одном из самых важных опубликованных за последнее время международных документов ? совместном консенсусе Американской Диабетической Ассоциации (ADA) и Европейской Ассоциации по исследованию диабета (EASD), а также в недавно опубликованном Консенсусе Американской Ассоциации Клинических Эндокринологов (AACE)/ Американской Коллегии Эндокринологов (ACE). В этом обзорном документе специально оговаривается сравнение различных препаратов в виде следующего заявления: в настоящее время недостаточно данных, чтобы поддержать рекомендацию по какому-то конкретному классу сахароснижающих препаратов или их комбинации в отношении влияния на предупреждение осложнений. Поэтому, справедливо судить и сравнивать сахароснижающие агенты, так же, как и их сочетание, в первую очередь по их способности снижать и поддерживать уровень HbA1c, а также по их безопасности, специфическим побочным эффектам, переносимости, удобстве в применении?. Далее в документе подчеркивается особая роль инсулина в лечении СД, обосновывая это следующим: ? инсулин является самым мощным сахароснижающим препаратом; ? своевременное начало инсулинотерапии обеспечивает оптимальный контроль гликемии и, соответственно, улучшает прогноз СД 2 типа, замедляя развитие в организме необратимых изменений; ? доказано влияние интенсивной инсулинотерапии на предупреждение развития сосудистых осложнений при диабете; ? по мере прогрессирования диабета заболеванием труднее управлять; в этом плане инсулин даёт дополнительные преимущества, поскольку его действие не зависит от остаточной секреторной активности бета-клеток. В настоящих рекомендациях будут затронуты все этапы инсулинотерапии СД 2 типа: начало, оптимизация и интенсификация.

Patients with diabetes mellitus (DM) are predisposed to diffuse and rapidly progressing forms of atherosclerosis which significantly increasesthe probabilityof surgical revascularization of myocardium. However, unique pathophysiological features of atherosclerosis in DM patients are responsiblefortheirunusual reaction to an arterial injury associated with percutaneous coronary intervention (PCI).Numerousstudies showed that DM is an independentrisk factor of restenosis following successful balloon angioplasty or stenting of coronary arteries and significantly increases the need forsecondary myocardial revascularization that compromises the outcome of the treatment.Preliminary data indicate that the use of drug-releasing stentsdecreases the need for repeat interventions in both diabetic and non-diabetic patients without negative effect on certain clinical end-points, such asmyocardial infarction and mortality. Any surgical intervention causes less pronouncedimprovement of the clinical picture or prognosis in patients withfunctional class I or II angina of effort compared with optimal medicamental therapy. Surgical revascularization, PCI and aortocoronary bypasssurgery (ACB) is indicated to patients that remain symptomatic despite adequate conservative therapy. The choice of an optimal revascularizationstrategy is of primary importance for DM patients with multiple lesions in the coronary system. Randomized studies comparing multivascularPCI withballoon angioplasty and holometallic stents demonstrated the advantage of ACB for DM patients who showed a higher survival rate, lower frequencyof infarctions and secondary revascularization. Certain authors demonstrated that ACB surpasses PCI even when drug-releasing stents are used.It may be hoped that the ongoing randomized studies comparing the two modalities will help to develop the optimal strategy for myocardial revascularizationindiabetic patients.

В Российском консенсусе по терапии сахарного диабета (СД) детей и подростков представлены современные высокие требования к компенсации заболевания как наиболее эффективному и единственно возможному пути профилактики развития специфических сосудистых осложнений, а также пути ее достижения с помощью современных методов инсулинотерапии. Пособие содержит сведения по фармакокинетике современных видов инсулина, схемам их введения, проблемам инсулинотерапии и путям их решения. Особое внимание уделено наиболее современным и эффективным средствам лечения СД ? инсулиновым аналогам быстрого и пролонгированного действия, а также инсулиновым помпам. Подготовленный консенсус отражает современные взгляды на терапию СД у детей и подростков. Он основан на результатах значительных международных исследований и международном опыте, а также на результатах собственных исследований и большом опыте клинической работы, накопленном в отделении СД Института детской эндокринологии ФГУ Эндокринологический научный центр, где концентрируется наиболее сложный контингент больных из различных регионов нашей страны, с учетом стандартов экспертов Всемирной Организации Здравоохранения. консенсус? предназначается для специалистов, занимающихся проблемами диабета в органах здравоохранения, эндокринологов, диабетологов, педиатров и врачей общей практики.

There is a new class of drugs used to treat diabetes mellitus (DM). It has come into existence after long-term studies of the fundamentally new hemostastic mechanism in glucose regulation via the gastrointestinal hormones incretins. With the advent of this class of drugs that minimize routine adverse reactions (weight gain, glycemic risk, nephro-, hepato-, and cardiotoxic effects, etc.), there is hope for a delay in the progressive increase of secretory function and β-cell mass, which is inevitable during standard treatment (which presages the eventual need to initiate insulin therapy 7-10 years after the onset of the disease). The mechanism of action of incretins is considered. The place of novel agents (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) in the total pattern of treatment for type 2 DM, indications for and contraindications to their use, benefits versus traditional glucose-lowering therapy (the inestimable advantage of these drugs is no risk for hypoglycemia), and prospects for their future application are discussed.

Diabetes mellitus is a most serious socio-medical and economic problems facing health authorities throughout the world. A major threat is vascularcomplications of the disease. The currently available diagnostic tools, up-to-date means for monitoring glycemia, introduction of innovative insulinpreparations and hypoglycemic agents, development of high-technology therapeutic modalities may greatly improve disease prognosis, reduce the frequencyof chronic complications, related disablement and mortality rates. The targeted control of major risk factors, viz. hyperglycemia, hypertension,and dyslipidemia, during the patients lifetime starting from the onset of diabetes remains the most promising strategy for the prevention of diabeticcomplications. An indispensable condition for efficacious management of diabetes is the elaboration of active screening programs for the early diagnosisof complications and optimal organization of the clinico-diagnostic process in the framework of multidisciplinary approach.

Type 1 diabetes mellitus (DM1) is associated with compromised (defective) immunologic tolerance to autoantigens and selective destruction of pancreatic B-cells by CD4+ (effector) and CD8 (cytotoxic) lymphocytes. The mechanisms of autotolerance involve CD4+CD25+high T-regulatory cells (Treg) whose suppressor activity depends on the expression of the FoxP3 gene. Aim. Detection of quantitative and functional alterations at the level of regulation of immunity in subjects at risk of DM1 and patients with different duration of DM1. Materials and methods. 116 patients (67 men and 49 women) with different duration of DM1. The risk group was comprised of 33 subjects (10 men and 23 women), control group included 16 subjects. In all cases, HLA genotyping was performed, autoantibodies to GDC, insulin and tyrosine phosphatase, islet cell antigens were determined, subpopulation composition of CD3+, CD4+, CD8+, CD38+, HLA DR+, CD25+, CD4+25+ lymphocytes and their functional activities (FoxP3 gene expression) studied, C-peptie and HbA1c levels measured. Results. A tendency toward a rise in Cd25+ and CD4+25+ T-lymphocytes and a decrease in FoxP3 expression was documented in the risk group compared with control (p0.05) but their functional activity was lower (p

Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD). Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR) > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33), 2 - DM2 patients with diabetic nephropathy (n=24), 3 - DM2 patients with ischemic nephropathy (IN) (n=33) verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta), 4 - DM1 patients with DN (n=30). Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU) by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy). Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b), angiotensin II (AT II), monocyte chemoattractant protein (MCP-1),regulated on activation normal T cell expressed and secreted (RANTES), adhesion factors (intracellular adhesion molecule (ICAM-1), vascular celladhesion molecule (VCAM-1) vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylargnine (ADMA), homocysteine(HCYST), metalloproteinases (MMP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-I). Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6) and extracellular matrix degradation factor(MMP-9) levels compared with patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF), and endothelium-affecting factors (ADMA, homocysteine). Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.

Aim. To analyse frequency distribution of alleles and genotypes of -23 HphI, a polymorphic marker of the INS gene, for evaluation of its associationwith DM1. Materials and methods. The study included two group of subjects: healthy ones and DM1 patients. Genotyping was performed by real time amplification. Results. Comparative analysis demonstrated association between -23 HphI polymorphic marker of INS gene, and type 1 diabetes mellitus. Conclusion. The use of the case-control method revealed association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus.

Aim. To evaluate clinical efficiency of sulodexide (glycosoaminoglycan) for the treatment of patients with type 2 diabetes mellitus (DM2) and diabeticnephropathy (DN) at the stage of microalbuminuria (MAU). Materials and methods. A total of 30 patients with DM2 and MAU were examined 15 of whom were given sulodexide (200 mg daily) for 6 months.The following parameters were measured before, 3 and 6 months after the onset of therapy: HbA1c level, biochemical characteristics, highly sensitiveCRB, MAU in morning urine samples, soluble intercellular and vascular cell adhesion molecules-1, blood coagulation and anticoagulation factors(PTI, fibrinogen, thrombin time, coagulation factors VII, VIII, X, Willebrand factor), tissue plasminogen activator, and its inhibitor. Results. Sulodexide produced significant positive effect on albumin excretion in urine. It exerted antithromotic and profibrinolytic action and improvedendothelial function. Taken together, these properties of sulodexide give reason to recommend it as a protector of different vascular segments. Conclusion. Significant positive effect of sulodexide on albumin excretion in urine coupled to its multifactor activity, convenience of therapeutic application,low risk of complications, good tolerability, and safety in aged patients with DM2 permit to consider it as a promising tool for the treatmentof DM2 with MAU.