Type 2 diabetes and prediabetes prevalence in patients with different risk factor combinations in the NATION study

BACKGROUND: Type 2 diabetes (T2D) is multifactorial disease. NATION epidemiological study may provide the information about the prevalence of T2D and prediabetic state in patients with different risk factor combinations in Russian population. AIMS: To evaluate the prevalence of T2D and prediabetic state in NATION cohort depending on the amount of diabetes risk factors. MATERIALS AND METHODS: NATION is an epidemiological, cross-sectional study, designed to assess the prevalence of T2D in Russian adult population, where HbA1c was used to establish T2D (HbAc≥6,5%) and prediabetes (5,7%≤HbA1c<6,5%). Patients with T2D were either previously diagnosed or newly diagnosed. Current study presents an additional analysis of NATION cohort focused on the prevalence of T2D and prediabetic state among patients with different risk factor combinations. RESULTS: T2D and prediabetic state prevalence gradually increased among patients with following risk factors (prevalence of T2D and prediabetes respectively): low physical activity (4,3%, 18,3%), rare fruit and vegetable consumption (4,8%, 18,7%), T2D family history (7,7%, 20,3%), age ≥45 years (9,5%, 31,3%), obesity grade 1 (9,6%, 30,3%), obesity grade 2 (14,6%, 37,8%), obesity grade 3 (20,1%, 39,7%), hypertension (14,7%, 38,2%), history of diabetes during pregnancy (14,1%, 24,7%). Prevalence of T2D with single and multiple risk factors was compared to the prevalence of T2D in young patients (<45 years) without additional diabetes risk factors. Age ≥45 years was associated with 7-fold increase in T2D prevalence; obesity – 8,8-fold; family history – 5,7-fold; hypertension – 10,8-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors). When one patient had several risk factors combined, the prevalence of T2D increased progressively: combination of age ≥45 years and family history led to 10,7-fold rise; combination of age ≥45 years and BMI≥30kg/m2 – 11,2-fold; combination of age ≥45 years, family history and BMI≥30kg/m2 – 15,3-fold; combination of age ≥45 years, family history, BMI≥30kg/m2 and hypertension – 19,1-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors). CONCLUSIONS: Presence of multiple risk factors, such as age ≥45 years, obesity and hypertension led to progressive increase in the prevalence of T2D and prediabetic state. These data are important to identify patients at the highest risk of T2D among Russian population

Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression

Background: The fusion protein E2A-PBX1 induces pediatric B cell leukemia in human. Previously, we reported oncogenic interactions between homeobox (Hox) genes and E2A-PBX1 in murine T cell leukemia. A proviral insertional mutagenesis screen with our E2A-PBX1 B cell leukemia mouse model identified Hoxa genes as potential collaborators to E2A-PBX1. Here we studied whether Hoxa9 could enhance E2A-PBX1 leukemogenesis. Results: We show that Hoxa9 confers a proliferative advantage to E2A-PBX1 B cells. Transplantation experiments with E2A-PBX1 transgenic B cells overexpressing Hoxa9 isolated from bone marrow chimeras showed that Hoxa9 accelerates the generation of E2A-PBX1 B cell leukemia, but Hoxa9 is unable to transform B cells alone. Quantitative-reverse transcriptase polymerase chain reaction analysis demonstrated a strong repression of B cell specific genes in these E2A-PBX1/Hoxa9 leukemias in addition to Flt3 activation, indicating inhibition of B cell differentiation in combination with enhanced proliferation. Overexpression of Hoxa9 in established E2A-PBX1 mouse leukemic B cells resulted in a growth advantage in vitro, which was also characterized by an enhanced expression of Flt3. Conclusions: we show for the first time that Hoxa9 collaborates with E2A-PBX1 in the oncogenic transformation of B cells in a mouse model that involves Flt3 signaling, which is potentially relevant to human disease

Trends in the epidemiology of diabetic retinopathy in Russian Federation according to the Federal Diabetes Register (2013–2016)

Background: Diabetic retinopathy (DR) is one of the most common causes of blindness in patients with diabetes mellitus (DM) that is why its necessary to study the epidemiological characteristics of this complication. Aims: The aim of the study was to evaluate the epidemiological characteristics of DR and blindness in adult patients with type 1 (T1) and 2 (T2) diabetes in Russian Federation (RF) for period 201316years. Materials and methods: Database of Federal Diabetes register, 81st regions included in the online register. Indicators were estimated per 10,000 adult DM patients (18years). Results: In 2016 the DR prevalence in RF was T1 38,3%, T2 15,0%, with marked interregional differences: 2,666,1%, 1,146,4%, respectively. The DR prevalence within 20132016 years was: T1 3830,93805,6; T2 1586,01497,0. Trend of new DR cases/per year increased: T1 153,2187,8; T2 99,7114,9. The structure of new cases of DR in 2016: non-proliferative stage (T1 71,4%, T2 80,3%), pre-proliferative stage 16,4%, 13,8%, proliferative 12,1%, 5,8%, terminal 0,2%, 0,1%, respectively, these data indicated the earlier detection of DR. The mean age of DR diagnosis increased: T1 by 1,2 years, T2 by 2,6. The average DM duration of DR determine increased T1 9,613,1 years, T2 6,09,1. The prevalence of blindness tends to decrease: T1 92,390,8; T2 15,415,2/10.000 DM adults. The amount of new cases of blindness/per year increased: T1 4,34,6; T2 1,21,4. The mean age of blindness increased: T1 39,141,6 years, T2 64,467,4; the mean duration of diabetes before blindness occur (from the time of DM diagnosis) increased: T1 20,221,2 years, in T2 10,711,3. We observed growth of DR treatment (laser surgery, vitrectomy, anti-VEGF medication) but the frequency of use in T2 patients is about 2 times less than in T1. Conclusions: There was a decrease in the overall incidence of eye damage in diabetes (DR and blindness) in the analyzed period in RF. DR and blindness develops at advanced age and with a longer duration of diabetes. As the main directions of eye care development in diabetes it is necessary to standardize primary care in the regions, to unify the examination algorithms and methods of early diagnostic, to increase the continuity and interaction of endocrinologists and ophthalmologists in managing patients with diabetes in order to prevent the development of new cases of vision loss

Diabetes mellitus type 1 in childhood

Public organization “Russian Association of Endocrinologists”. Clinical guidlines

Materials of scientific and practical conference «Dietoogy In Practice Of Endocrinologist» at the VIII (XXV) Russian Diabetology Congress With International Participation «Diabetes Mellitus – XXIth Century Pandemia»

The scientific-practical conference Dietoogy In Practice Of Endocrinologist was held during the VIII Russian diabetology congress with international participation “Diabetes Mellitus – XXIth Century Pandemia”. It was chaired by Academician of RAS M.V. Shestakova (Moscow), Professors L.A. Ruyatkina (Novosibirsk ) and L.A. Suplotova (Tyumen). The expediency of this event was dictated by the necessity to create a unified national regulated guidelines for the diet therapy of obesity and associated diseases for the medical community and patients. The program of the meeting included a discussion about the formation of a healthy diet and its effect on the body, starting from the pregnant women, fetal development, the breastfeeding period, in the period of perimenopause and postmenopause, in the presence of concomitant pathology of heart and kidneys

Diagnosis and rational treatment of painful diabetic peripheral neuropathy: an interdisciplinary expert consensus

Diabetic peripheral neuropathy is a common chronic complication of diabetes mellitus, significantly impairing well-being, quality of life and functioning of patients. The prevalence of diabetic peripheral neuropathy in the Russian Federation ranges from 0.1% to 67.2% in type 1 and from 0.1 to 42.4% in type 2 diabetes mellitus. However, based on the large-scale epidemiological studies, the true prevalence of diabetic peripheral neuropathy is much higher (50 to 70%), with its painful variant occurring in 16% to 30% of patients. Despite the fact that diabetic peripheral neuropathy remains the most common chronic complication of diabetes mellitus, its diagnosis and therapy leave much to be desired. To optimize diagnostic and treatment approaches to painful diabetic peripheral neuropathy, a group of experts representing the leading Russian professional medical associations has developed clinical guidelines for the diagnosis and rational therapy of patients with painful diabetic peripheral neuropathy. This document presents practical aspects of the clinical diagnosis of painful diabetic peripheral neuropathy and an algorithm for differential diagnosis of pain in the lower extremities in patients with diabetes mellitus. The use of symptomatic analgesics with central action, such as anticonvulsants, antidepressants and opioids, is based on the main aspects of neuropathic pain pathophysiology. The characteristics of each drug class are given, with consideration of evidence on their efficacy, tolerability, and the possibility of combination therapy. The data on the first, second, and third lines of agents is presented in accordance with several international clinical guidelines. The need for a tailored drug choice, taking into account the evidence-based data on their efficacy and safety, concomitant drug therapy, tolerability, cost and preferences of the patient, age of the patient and concomitant disorders, is emphasized

Diabetes mellitus type 2 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.&nbsp

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 9th edition

Dear Colleagues! We are glad to present the 9th Edition (revised) 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, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, 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 in the world increased during the last decade more than two-fold, reaching some 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 million by 2045. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) – Type 2 DM, 6% (256 202) – Type 1 DM and 2% (89 870) – other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. In сurrent edition of the “Standards”: New goals of glycemic control for the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Grou

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 10th edition

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized 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), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, 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 in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic 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.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.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, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Grou