Olga Konstantinovna Vikulova

National register of diabetes mellitus in Russian Federation.

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 HbA 1c ) and according to the data of online register.

Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the federal diabetes registry

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 <7% in 33.4%, 7%–7.9% in 28.3%, 8%–8.9% in 16.2%, and ≥9.0% in 22.1% of patients. HbA1c levels in T2DM was <7% in 52.1%, 7%–7.9% in 29.1%, 8%–8.9% in 10%, and ≥9.0% in 8.7% of patients. Conclusions . This study evaluated the increase in DM prevalence in the Russian Federation in 2016 and in the dynamics of 2013–2016, which was mainly due to T2DM. An increase in patients with a target HbA1c level <7% and a decrease in the proportion of patients with severe uncontrolled DM was observed; however, the treatment effectiveness of this key indicator was unsatisfactory, i.e. less than a third of the patients with DM. In the dynamics of 2013–2016, an increase in mean life span for patients with T2DM and mortality reduction in patients with T1DM and T2DM was observed. The frequency of diabetic complications varied widely, which may reflect differences in the quality of specialised care in different regions.

Diabetes mellitus and chronic kidney disease: achievements, unresolved problems, and prospects for therapy

The dramatic increase in the number of patients with diabetes mellitus (DM) and chronic renal disease (CRD) in the recent years emphasizes the closeassociation between the two conditions and the leading role of DM in the development of renal pathology. Diabetology and nephrology are highly costlybranches of public health, and the burden of substitution renal therapy in DM patients continues to grow. The necessity of a renoprotection programat the early stages of DM for the prevention or delay of terminal renal insufficiency becomes increasingly clear. Such program should be based on theconceptual model of the evolvement of diabetic nephropathy as a consequence of combined action of metabolic and hemodynamic factors modulatedby genetic ones.

Pre-clinical markers for diagnosis of diabetic nephropathy in patients with type 1 diabetes mellitus

Due to progressive nature of diabetic nephropathy (DN) and limited effectiveness of therapeutic efforts at clinically overt stages, diagnosisof pre-clinical (and, therefore, potentially reversible) DN is especially important. To date, however, test for microalbuminuriaremains the only technique applicable for early diagnostics of DN.Current review addresses search for potential markers of pre-clinical stage of DN in patients with type 1 diabetes mellitus and embracesdata from latest experimental and clinical studies in this area.

Renal allograft nephropathy in patient with type 1 diabetes mellitus

Renal allotransplantation is the most effective and safest mode of renal replacement therapy in patients with diabetes mellitus (DM),and currently is recognized as method of choice for patients with end-stage renal disease. Due to variety of factors damaging transplantedkidney in patients with DM, issues of long-term survival of the graft constitute a serious problem. Therefore, special attentionshould be directed at correction of rejection risk factors in order to prolong graft survival - and prevent development and progressionof chronic allograft nephropathy.

Biosimilars: presumption of guilt

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.

Prevalence of renal lesions in patients with type 1 and 2 diabetes mellitus in the Russian Federation

Aim. To study the prevalence of renal lesions in adult patients with type 1 and 2 diabetes mellitus in the Russian Federation. Materials and methods. A total of 7174 patients with DM1 and DM2 were examined in 20 regions of the Russian Federation for blood HbA 1c creatinine,urea, and cholesterol levels, albumin excretion in a single urine sample, AP, and eye fundus condition. Albumin concentration from 20 to 200mg/l was regarded as microalbuminuria (MAU) that above 200 mg/l as proteinuria (PU). The glomerular filtration rate (GFR) was calculated fromCockroft-Gault formula. Statistica-6 program was used for statistical treatment of the results of the study. They are represented as median, 25th and75th percentile values (Me [25%;75%]). Differences between all parameters is considered significant at p Results. Pathologic albumin excretion was documented in 42,1 and 45,3% of the DM1 and DM2 patients. Its prevalence increased with age andDM duration as well as at poor AP and glycemic control. Stage 2 chronic renal disease developed in 16,5 and 23,7%, stage 3 in 4,2 and 6,3%,stage 4-5 in 0,9 and 0,2% of the DM1 and DM2 patients respectively. 15,0 and 41,2% of DM1 and DM2 patients with MAU needed additionalexamination to elucidate non-diabetic origin of CRD. 40% of the DM2 patients with impaired GFR and poor glycemic control had to be transferredto insulin therapy.

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus

AIM The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

Diabetes mellitus in children and adolescents according to the Federal diabetes registry in the Russian Federation: dynamics of major epidemiological characteristics for 2013–2016

Background : The data of the register is the main source of up-to-date information about patients with diabetes mellitus (DM). It’s very important for improving the quality of medical care organization. Aims : to analyze the main epidemiological DM characteristics in Russian Federation (RF) (prevalence, incidence, mortality) in children and adolescents, to assess the dynamics of these parameters for the period 2013 – 2016, to analyze the status of compensation for carbohydrate metabolism, therapy of DM1, prevalence of diabetic complications and the reasons for hospitalizations in these age groups. Materials and methods : The database of Federal DM registry of 81 regions was included in the online system. Results : The total number of patients under the age of 18 with DM in RF on 31.12.2016 was 33081 people, there were 95,9% (31727 people) with DM1 and 4,1% (1354 patients) with DM2. The prevalence of DM1 in 2013–2016 in children: 81.0 – 91.4 / 100 ths., in adolescents – 212,8–209,5 / 100 ths. The DM1 incidence/100 thousand population in 2016 in children was 14,2/100 ths., in adolescents 10,0/100 ths. HbA1c levels in DM1 was in children: 9% in 35% of the patients; in adolescents 9% in 45% of the patients. Among complications in children and adolescents with DM1, diabetic neuropathy is the most often recorded (in 10,9% of cases and 40,8%, respectively); among DM2 patients, diabetic neuropathy is registered in 4,7% and 8,8% in children and adolescents, respectively. There are associated diseases in DM2 patients – arterial hypertension and dyslipidemia. 43,8% of children and 49,2% of adolescents were hospitalized in the anamnesis, most hospitalizations in 2016 (children 71,9%, adolescents 67,1%) were due to diabetes. Conclusions : It is established that in the dynamics of 2013–2016 the prevalence of DM1 in children continues to increase, with relatively stable indicators in adolescents. According to the register, during last two years there has been a decrease in the incidence of DM1 and, on the contrary, an increase in the prevalence/incidence of DM2 in children. Significant interregional differences in the level of incidence/prevalence have been established, especially in regions located in various geographic regions of the RF. The frequency of diabetic complications in children and adolescents with diabetes varies. There is an association of hospitalizations with higher HbA1c level. In the structure of therapy of this age group the ratio of insulin therapy in syringes-pens and pump therapy is 80.9% / 15.1% according to the register.

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population

Background The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. Methods The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively. Results The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function. Conclusion In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.