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According to the “Federal Law on the Fundamentals of Protection of the Public Health”, medical care for patients should be provided in accordance with National Russian guidelines for the relevant nosology, which are based on the principles of evidence-based medicine. The article presents an analysis of the compliance with the completeness of implementation of National Russian guidelines in the treatment of patients with type 2 diabetes mellitus (DM 2) in real clinical practice. The analysis of the actual state of management of DM 2 patients was carried out from the Federal Register of diabetes as of 01.01.2023. Incomplete compliance with the guidelines on the frequency of measuring glycated hemoglobin, the rate of intensification of hypoglycemic therapy, and the appointment of new classes of hypoglycemic drugs was established. Possible reasons for the identified discrepancies between real practice and guidelines requirements are discussed, as well as possible measures to overcome these discrepancies.

The clinical blood metabogram (CBM) was developed to match a tailored analysis of the blood metabolome to the time, cost, and reproducibility constraints of clinical laboratory testing. By analyzing the main blood metabolite groups, CBM offers clinically relevant information about the intake of low-molecular substances into the organism, humoral regulation, liver function, amino acid level, and the lipid and carbohydrate metabolism. The purpose of this work was to investigate the relevance of using the CBM in patients with diabetes mellitus. For this, a CBM was obtained for 18 healthy individuals, 12 individuals with prediabetes, and 64 individuals with type 2 diabetes mellitus, separated into groups according to fasting blood glucose and oral glucose tolerance tests. The results showed that the CBM reveals diabetes-associated metabolic alterations in the blood, including changes in the levels of carbohydrates, ketone bodies, eicosanoids, phospholipids, and amino acids, which are consistent with the scientific data available to date. The CBM enabled the separation of diabetic patients according to their metabolic metabotypes, providing both a general overview of their metabolic alterations and detailing their individual metabolic characteristics. It was concluded that the CBM is a precise and clinically applicable test for assessing an individual’s metabolic status in diabetes mellitus for diagnostic and treatment purposes.

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 Group

IntroductionUntil recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation.Materials and methodsThe cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/).ResultsThe median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p

While accidentally detecting an adrenal gland lesion (incidentaloma) during a routine computed tomography (CT) scan, the radiologist should correctly interpret revealed changes. The most common lesion is adenoma with high lipid content, but a lipid poor adenoma, pheochromocytoma, adrenocortical cancer, metastasis and other less common adrenal diseases are also worth of attention and require detailed knowledge of their CT semiotics. The article presents criteria of differential diagnosis of the adrenal incidentalomas on the basis of which an algorithm of differential diagnosis was proposed for the most common adrenal lesions.

Aim. To study the clinical, biochemical characteristics, treatment results and follow-up of patients with ectopic ACTH syndrome EAS (ACTH adrenocorticotropic hormone ). Materials and methods. A retrospective, observational, single-center study of 130 patients with EAS. Demographic information of patients, medical history, results of laboratory and instrumental investigations at the pre- and postoperative stages and follow-up of EAS were analyzed. Results. The mean age at the diagnosis ranged from 12 to 74 years (Me 40 years [28; 54]). The duration of the disease from the onset of symptoms to the verification of the diagnosis varied from 2 to 168 months (Me 17.5 months [7; 46]). Eighty-one (62,3%) patients had bronchopulmonary NET, 9 thymic carcinoid, 7 pancreatic NET, 5 pheochromocytoma, 1 cecum NET, 1 appendix carcinoid tumor, 1 medullary thyroid cancer and 25 (19.2%) had an occult source of ACTH. The median follow-up period of patients was 27 months [9.75; 61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.1%) patients, bilateral adrenalectomy was performed in 23 (18%) patients, in 16 of them there was an occult source of ACTH-producing NET and in 7 patients in order to control hypercortisolism after non-successful surgical treatment. Regional and distant metastases were revealed in 25 (19.2%) patients. At the time of the last observation 59 (72%) patients were exhibited a full recovery, 12 (14.6%) had relapse of the disease and 26 (20%) died from multiple organ failure (n=18), pulmonary embolism (n=4), surgical complications (n=2), disseminated intravascular coagulation syndrome (n=1) or COVID-19 (n=1). Conclusion. In our cohort of patients bronchopulmonary NET are the most frequent cause of EAS (62.3%). Surgical treatment leads to remission of hypercortisolism in 72% cases; the proportion of relapse (14.6%) and fatal outcome (20%) remains frequent in EAS.

BACKGRAUND: The need to create a national questionnaire for screening the population for disorders of carbohydrate metabolism.AIMS: Develop a highly specific and sensitive questionnaire-calculator of the risk of prediabetes (PreD) and diabetes mellitus type 2 (DM2T) based on depersonalized data of individuals who have these diagnoses confirmed in the national epidemiological study NATION.METHODS: The express method of prediabetes (PreD) and diabetes mellitus type 2 (DM2T) risks has been created, validated and proposed for clinical usage for the first time in the Russian Federation, it was based of NATION epidemiologic study database (more than 26 000 participants). The following mathematical instruments have been used: mathematic modelling, main components methodology, binary variables, correlation analysis and single-factor analysis of variance.RESULTS: Highest coefficients of logistic regression for PreD (p

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushing’s syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive. AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA). MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushing’s Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushing’s syndrome manifestation. RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,5–12,7 nmol/l (5–95 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST – 0,838 (95% СI 0,772–0,905), for blood cortisol in 1-mg DST – 0,965 (95% CI 0,939–0,992) and for late-night salivary cortisol – 0,925 (95% CI 0,882–0,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and – 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA. CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity.

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

BACKGROUND: Glikogemoglobin (HbA1c) is a key clinical marker for evaluating the effectiveness of glucose-lowering therapy for patients with diabetes mellitus (DM) and the quality of diabetic care. AIMS: to conduct dynamic monitoring of the quality of glycemic control in DM patients based on a comprehensive examination in mobile medical center (Diamodul) during repeated visits to the regions in 2019 compared with visits of Based Federal program “Diabetes Mellitus” (2005–2010) and data of the National diabetes register (NDR). MATERIALS AND METHODS: The object of the study: patients with T1DM and T2DM examined in Diamodul in 2019 in Voronezh region (Vr), Krasnodar region (Kr) (n = 600), there were “dynamic” group of re-examined (Vr n = 224; Kr n = 113), “random” group of new patients (Vr n = 72; Kr n = 191); group of adult patients from NDR with indicated HbA1c in 2019 (n = 2410067). RESULTS: According to Diamodul, the HbA1c levels are significantly worse than they were reported to NDR: the proportion of patients achieved HbA1c

In 2020, the world is facing a historically unparalleled public health challenge associated with the invasion of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This is also a challenge for the healthcare systems worldwide. Patients with diabetes mellitus (DM) are most vulnerable to COVID-19 because of the peculiarities of their immune response to a virus attack and due to their high susceptibility to viral activity because of hyperglycemia and other comorbid conditions and obesity that often accompany DM. The severity of the COVID-19 disease requires a mandatory review of the usual anti-hyperglycemic therapy. Maintaining optimal glycemic control and preventing the development of ketoacidosis remain extremely important; therefore, insulin becomes the priority drug for glycemic control in most cases. The search for new drugs to fight against the coronavirus infection continues with new randomised clinical drug trials being launched. Innovative anti-diabetic agents are also being tested as candidates for potentially effective anti-coronavirus agents.

Public organization “Russian Association of Endocrinologists”. Clinical guidlines.

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

BACKGROUND: One of the consequences of obesity for the female body is a decrease in fertility. It is shown that impaired reproductive function in obese patients can be associated, in particular, with a decrease in ovarian reserve. AIMS: To evaluate the ovarian reserve function in female patients of reproductive age with different classes of obesity in comparison with women without obesity. MATERIALS AND METHODS: This study evaluated 320 caucasian women, age 20-30 years, without obesity (BMI

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 Group

The Federal Diabetes Register (FDR) has been conducting clinical and epidemiological monitoring of diabetes in the Russian Federation (RF) since 1996. Its methodological and organizational reference centre is Endocrinology Research Centre. FRD was created by Order of the Ministry of Health of RF №404 of December 10, 1996 as part of implementation of the Federal target program "Diabetes Mellitus". Over the 20-year period, the registry has played a key role in assessing the prevalence of diabetes and diabetic complications in the RF. Since 2014, the register has been transformed into online system as a unified federal database with an authorized code access. Personal data protection is carried out in accordance with the laws and regulations of the Russian Federation.

BACKGROUND: The prevalence of dysnatremia varies widely (from 1 to 63%), and depends on comorbidities, the effects of more than 18 hormones and hormone-like substances, which confirms the importance of maintaining blood sodium levels in the tight physiologic range and makes it possible to consider its deviations as an endocrine pathology. Both hypo- and hypernatraemia are associated with a multiple increase in mortality, risk of fractures, and gross balance disturbances. At the same time, the clinical manifestations of dysnatremia are not specific, reflect an osmotically mediated decrease in brain function, which potentially may be missed in clinical practice. AIMS: to study the specifics of diagnosis, differential diagnosis and treatment of dysnatremia states by specialist doctors using a sociological survey method. MATERIALS AND METHODS: A cross-sectional sociological uncontrolled study was conducted by questioning doctors about hypo- and hypernatremia using the online questionnaire “Questionnaire on hypo-and hypernatremia in clinical practice” created on the Google forms platform. The invitation to fill in the questionnaire was sent to the email addresses included in the database of the Russian Association of Endocrinologists. A total of 353 completed questionnaires were received. RESULTS: The poll demonstrated a low frequency of determining blood sodium levels - less than 38% of specialists prescribe sodium in more than half of the cases, including the cases of diseases associated with dysnatremia, which correlates with less practical experience of doctors. The overwhelming majority of endocrinologists (82%) in their clinical practice encounters deviations of the sodium levels in patients, but only 6% recognize the possession of the competence of managing patients with dysnatremia. The discrepancy between the lower limit of normal range to 135-136 mmol/l was observed in 22% (62/278), the inconsistency of the upper normal limit to 145-146 mmol/l - in 47% (131/278) of laboratories, and in 33% (41/278) laboratories, which are used by doctors, there was a discrepancy along both limits of the reference interval. The presence of a hypertonic solution (3%) of sodium chloride in a hospital was noted only by 38% of respondents. Conclusions: There is an unphysiological variation in reference intervals for blood sodium concentration in 55% of laboratories, a low frequency of sodium levels evaluation in the blood (in more than half of clinical situations only 38.2% of doctors prescribe the estimation of blood sodium level) and the lack of educational competence in managing patients with syndromes of hypo- and hypernatremia in 94% of endocrinologists.

Present literature review provides information about clinical trials that evaluated the association of the carriage of antithyroid antibodies (ATA) and the reduction of the ovarian reserve, as well as the effectiveness of assisted reproductive technologies. The ambiguity and sometimes the opposite of the conclusions of different authors, makes it possible to recommend a balanced attitude to the advisability of screening for ATA in women with a reproductive dysfunction as well as the therapeutic measures proposed in some guidelines based on the results of such examination.

Background: Disorders of water and electrolyte balance, hyper- and hyponatremia, are common postoperative complications of transsphenoidal neurosurgical interventions and are found in up to 3040% of cases. At the same time, delayed hyponatremia is the main cause of repeated hospitalizations of patients, and the risk factors/pathogenetic mechanisms responsible for the development of postoperative hyponatremia have not been fully investigated. Aim: To determine the frequency of water-electrolyte disturbances and to identify predictors of dysnatriemia states in patients after transnasal adenomectomy. Materials and methods: A retrospective single-site study included an analysis of electronic medical records of patients who underwent transnasal neurosurgical interventions for benign tumors of the pituitary gland (n = 416). The diagnostic and prognostic factors for the development of postoperative water-electrolyte disorders were evaluated. Results: The prevalence of hyponatremia in the total group of patients was 7.2%, and for hypernatremia it was 3 times higher 24.3%, with these indicators being kept stable through the years of surgery (p 0.05; 2 with the Yeats correction). 66 (16%) of the operated patients, the sodium level in the early (05 day) and 157 (38%) patients in the later (6+ day) postoperative period was not determined, which may underestimate the identification of the most dangerous delayed postoperative hyponatremia. When analyzing the main clinical and laboratory characteristics of patients with hypo-, normo- and hypernatremia, no statistically significant differences were found between the parameters characterizing natremia, the osmolality of blood and urine, the frequency of determining blood sodium in different time intervals of the postoperative period. Complications of the main diagnosis (diabetes mellitus, coronary heart disease and arterial hypertension), selected parameters of pathological examination (identification of neurohypophysis cells, adenohypophysis, oxyphilic, basophilic or chromophobic cells, as well as other structures that are not part of the pituitary gland) and the operation protocol (bleeding, coagulation of sellar structures, liquorrhea, excision of the pituitary gland), did not differ between groups. In the hypernatremia group, the tumor volume in quantitative representation was lower than in the normo- and hyponatremia groups (1.0 ml vs. 1.5 and 1.5 ml, respectively). The number of neurosurgical interventions performed in a patient did not differ between the study groups. Conclusions: After transnasal adenomectomy, hypo- and hypernatremia occur in 7.2% and 24.3%, respectively, and do not depend on the presence of complications of the underlying disease, the parameters of the pathomorphological protocol, the appearance of postoperative hypopituitarism or the course of the operation itself. For the timely detection of disorders of water and electrolyte metabolism, the implementation of blood sodium testing in the early and late (6+ day) postoperative period is necessary in management of patients after transnasal adenomectomy.

BACKGROUND: There is an interaction between cell-mediated pathway of the vessel calcification and atherosclerosis processes. In some studies the relation beeen circulating osteogenic progenitor cells and cardiovascular diseases was shown. Though its role in the development of cerebrovascular diseases (CVD) in Type 2 diabetes mellitus (T2DM) remains unknown. AIM: To study the level of circulating endothelial (CD34 + VEGFR2 +) and osteogenic (CD34 + OCN +) progenitor cells in patients with CVD and T2DM. METHODS: We observed patients with CVD (coronary artery disease and / or chronic limb threatening ischemia) with T2DM and without T2DM. Patients with CVD and T2DM were included in group 1 patients with CVD and without T2D were included in group 2. The level of CD34 + VEGFR2 cells and CD34 + OCN+ cells was determined by flow cytometry.There were no differences in the age, gender, lipid profile, body mass index, creatinine clearance, myocardial revascularization and lower limb revascularization between the 2 groups.The level of CD34 + VEGFR2 cells and CD34 + OCN+ cells was determined by flow cytometry. The number of cells was determined by a percentage of the number of CD34+ cells. RESULTS: We observed 71 patients (38 women, mean age 67 years [62, 74]). Forty six patients were included in group 1 (28 women, mean age 68 years [63;75], 25 patients (10 women, 66 years [55;72]) were included in group 2. We found that in patients with CVD and T2DM demonstrated higher amounts of CD34+OCN+ cells than CD34+VEGFR2+ cells. (29.7% [26.2;36.1] and 11.8% [9.57;17.2], p

BACKGROUND: Cardiovascular diseases (CVD) are the main cause of death for patients with diabetes mellitus (DM). AIMS: To evaluate the CVD epidemiology: coronary heart disease (CHD), myocardial infarction (MI) and cerebrovascular diseases in adult patients with type 1 (T1DM) and type 2 (T2DM) diabetes, compare dynamics with data of implementation of the Federal Program «Diabetes mellitus» in 2007–2012 and over the online period 2013–2016. MATERIALS AND METHODS: The database of the Federal Diabetes register (81 regions at 12.2017). We estimated prevalence and incidence rates/10 thousand (th) adult DM patients over 18 years. RESULTS: The prevalence of CVD for the period 2007 – 2016 significant decreased in CHD for T1DM from 14,9% to 3,5%, for T2DM from 20,1% to 11,7%; MI for T1DM from 5,7% to 1,3%, for T2DM from 7,6% to 3,5%; cerebrovascular diseases for T1DM from 4,9% to 1,7%, for T2DM from 7,6% to 4,3%, respectively. In 2013→2016 positive trends continued: MI for T1DM 8,2→5,9/10th patients, for T2DM 19,2→14,7/10th patients, respectively; CVD for T1DM 11,3→10,5, for T2DM 29,4→25,4/10th patients, respectively. There was a large heterogeneity of the prevalence of CVD in the regions. MI varied in patients for T1DM from 319/10 th patients to absence, for T2DM from 800 to 7/10 th patients; the development of cerebrovascular diseases for T2DM from 900 to less than 100/10 th patients, which is largely due to differences in their registration. A small number of cases may be due to insufficient filling of the database, the facts of a huge number require further analysis. The average age of development of MI had increased: for T1DM 51,2→53 years, for T2DM 63,5→65 years, cerebrovascular diseases for T1DM 52,3→52.5 years, for T2DM 65,2→66,5, respectively. CONCLUSIONS: The prevalence of CVD significantly decreased in the Russian Federation compared to 2007–2012, as well as for the period 2013–2016: the prevalence of CHD and cerebrovascular diseases declined, the number of new cases of MI decreased, the average age and duration of DM before the development of CVD significantly increased. These data reflect the results of the program for improvement medical care and prevention measures for patients with diabetes.

BACKGROUND:Patients with endogenous hypercortisolism have reduced bone mineral density (BMD) and trabecular bone score (TBS) that are the causes of secondary osteoporosis and low-traumatic fractures. It is well known that radical treatment (neurosurgery or radiosurgery) of Cushings disease leads to a decline of cortisol levels in all body fluids to normal values. However, it is still uncertain whether bone tissue structure, and particularly its microarchitecture, does recover in remission of the disease. AIMS:To evaluate an influence of hormone activity (presence or absence of remission) in patients with Cushing's disease on changes of bone structure measurements in accordance with DXA values (TBS, BMD, T- and Z-scores), as well as significance of such changes in 12 and 24 months after neurosurgical treatment. MATERIALS AND METHODS:In patients with confirmed active Cushing's disease (ACTH-producing pituitary adenoma) (n = 44) and in control group of healthy volunteers (n = 40), BMD in lumbar spine (L1-L4) and simultaneously TBS, in cut-off points before neurosurgical treatment (in both groups) and in 12 and 24 months after it (only in patients), were assessed. We diagnosed presence or absence of disease remission at cut-offs. All measurements were performed using a GE iDXA device (GE Healthcare Lunar, Madison, Wisconsin, USA). The TBS was calculated simultaneously from taken BMD scans, blinded to clinical outcome using TBS iNsight software v2.1 (Medimaps, Merignac, France). The activity of Cushings disease was evaluated using late-night salivary cortisol (LNSC, at 23:00). To determine the differences in DXA and TBS values before and after neurosurgical intervention depending on remission occurrence, covariate analysis (ANCOVA) was applied. RESULTS:There were found significant changes in TBS, BMD and T-score values in 12 months after neurosurgical treatment associated with presence or absence of disease remission (p = 0.039, 0.046 and 0.048, respectively). No differences in Z-score as well as in all measurements in 24 months, that might be associated with remission occurrence, were revealed. The gain in all DXA measurements (including TBS) during 24 months of observation period was statistically significant when analyzing data using Students paired t-test. However, the values corresponding to the age references had not been achieved for the specified time interval. CONCLUSIONS:Patients with Cushings disease have lower TBS values. In remission conditions TBS is getting significantly higher. The increase in BMD and TBS occurs during 24 months after achieving remission of Cushings disease but doesnt lead to a full restoration of normal bone mass and microstructure throughout observation period of 24 months.

Background: Patients with primary hyperparathyroidism (PHPT) have increased mortality risk predominantly attributed to cardiovascular disease. Taking the risk factors for cardiovascular disease into account, such as overweight, atherogenic dyslipidaemia, carbohydrate metabolism disorders and insulin resistance (IR), investigation on the the study of the state of carbohydrate and lipid metabolism in patients with PHPT will help to shed light on the pathogenic mechanisms of the disease and, perhaps, to complement the algorithm for selecting treatment strategies for patients with PHPT. Aims: To study the prevalence of carbohydrate and lipid metabolism disorders among patients with PHPT and to identify the relationship between these two disorders with the indicators of mineral metabolism. Materials and methods: A case-control study of a total of age-matched 256 female patients, 220 patients with PHPT and 36 healthy individuals. The group patients with PHPT were sub-divided into two groups, symptomatic and mild form of PHPT. To verify the form of PHPT, ultrasound examinations of the parathyroid glands and kidneys, two-energy x-ray absorptiometry, biochemical studies (concentration of total and ionised calcium, serum phosphorus and the activity of alkaline phosphatase) and assessment of parathyroid hormone concentration were performed. The relationship between form of PHPT and body weight were evaluated retrospectively according to the survey. Among the 109 participants with PHPT (symptomatic PHPT: 82 patients; mild PHPT: 27 patients) and healthy individuals, the biochemical and hormonal parameters of fat (lipid spectrum of blood) and carbohydrate metabolism (content of immunoreactive insulin, HOMA index, presence of fasting glycemia disorder, glucose tolerance disorders and type 2 diabetes mellitus) were evaluated. Results: The symptomatic PHPT was associated with low body mass index (BMI) while the mild PHPT with high BMI. During an oral glucose tolerance test, the postprandial glycemia in symptomatic PHPT was significantly higher than that in mild PHPT (p = 0.036). The content of immunoreactive insulin in the symptomatic PHPT was not correlated with the concentration of parathyroid hormone, but positively correlated with the concentration of ionised calcium in the blood (r = 0.31; p = 0.006). Patients with PHPT showed a direct positive correlation between BMI and IR index (r = 0.67; p < 0.001). It is shown that patients with PHPT have increased LDL content in the blood, and the actual blood lipid concentration is associated with the state of kidney function. Conclusions: The obtained data confirm the relationship between phosphorus–calcium metabolism disorders in PHPT and carbohydrate and lipid metabolism disorders. Prospective, controlled studies are warranted to better elucidate the causal relationships of mineral, carbohydrate and fat metabolism disorders in PHPT.

Background. Traditional endogenous stimulation of thyroid-stimulating hormone (TSH) by means of long-term withdrawal of thyroid hormones for radioiodine diagnostics and radioiodine therapy causes severe hypothyroidism, which worsens patients general well-being and may lead to side effects and cause tumor growth and dissemination. Exogenous stimulation with recombinant human TSH (rh-TSH, thyrotropin-alfa) causes short-term increases in TSH levels and does not have the above-mentioned side effects. Purpose. To estimate the efficacy and safety of rh-TSH in preparation of patients with well-differentiated thyroid cancer for radioiodine diagnostics and radioiodine therapy. Methods. We conducted an interventional single-center prospective unblinded uncontrolled study of the efficacy and safety of thyrotropin-alfa to prepare patients with well-differentiated thyroid cancer to radioiodine diagnostics and post-surgery radioiodine ablation. The study included 88 patients with well-differentiated thyroid cancer: 54 patients were prepared for post-surgery radioiodine ablation; 34 patients for radioiodine diagnostics to evaluate combined treatment efficacy and exclusion of tumor recurrence. The level of TSH, thyroglobulin, antibodies to thyroglobulin, whole body scintigraphy, and side effects were measured during exogenous stimulation with thyrotropin-alfa. Results. The level of TSH reached or exceed the target level (30 mIU/ml) 24 hours after the first injection of recombinant thyrotropin-alfa in 86% of patients; after 48 hours in 100%, the level exceeding 100 IU/ml was observed in 66 (75.1%) patients. The maximum levels of thyroglobulin and antibodies to thyroglobulin were reached 72 and 48 hours after the first injection, respectively. The injections of thyrotropin-alfa were well-tolerated by the patients. In the group for radioiodine diagnostics 2 (5.8%) patients complained of fatigue, 1 (2.9%) patient had signs of dyspeptic disorder, while in the group for radioiodine ablation 4 (7.4%) patients complained of fatigue, 1 (1.8%) patient had marked memory problems that disappeared later (they must have been caused by the patients advanced age (82 years)). Conclusions. Exogenous recombinant human thyroid-stimulating hormone (thyrotropin-alpha) is highly effective in preparation of patients with well-differentiated thyroid cancer for radioiodine diagnostics and radioiodine ablation. It does not have side effects, which are typical of withdrawal of thyroid hormones. The levels of thyroglobulin and antibodies to thyroglobulin measured 72 hours after the first injection of thyrotropin-alfa have the biggest diagnostic informative value.

Non-invasive brain stimulation belongs to most significant neurotechnologies which have arisen in the XXIth century and are characterized by universal medical importance. This group of methods comprises rhythmic transcranial magnetic stimulation (rTMS) and transcranial electric stimulation (transcranial direct current stimulation, tDCS). A spectrum of conditions for which these methods may be effective is steadily expanding and includes a variety of prevalent disorders of the modern society, such as obesity, depression, etc. The low effectiveness of lifestyle modification, as well as a wide range of pharmacological drugs side effects and high risks of surgical treatment determine the need to search for new safe methods of correction of eating behavior and obesity, a real pandemy of our society. A number of data suggest the patogenic role of changes of the frontal-striatal interactions in eating behanior disorders. Taking into account the existing models of the development of food dependence, the main approach to the use of rTMS and tDCS is stimulation of areas involved in cognitive control, such as the dorsolateral prefrontal cortex. Current data on studies of rTMS and tDCS in patients with impairment of eating behavior, as well as safety issues of using these techniques in routine clinical practice are reviewed.

Background: As in many other developed nations, the problem of obesity and type 2 diabetes is acute in Russia. In Russia, the only combination of sibutramine and metformine (Reduxin®Met) is authorized to reduce body mass and prevention development of type 2 diabetes mellitus or its complication. The article presents the results of the observational program “AVRORA”. Aim: Evaluation of the effectiveness and safety of Reduxin®Met (sibutramine + microcrystalline cellulose + Metformin) in patients with type 2 diabetes and alimentary obesity in routine clinical practice. Materials & methods: The observational program “AVRORA” was conducted from September 2016 to October 2017 under the auspices of the Endocrinological Scientific Center and the Russian Association of Endocrinologists. The “AVRORA” program was a multicenter, non-interventional study of patients to whom the attending physicians prescribed Reduxin®Met, a set (tablets + capsules), in accordance with the instruction for medical use as part of routine clinical practice. The treated group included patients of both sexes, aged 18–65 years, with an established diagnosis of obesity in combination with type 2 diabetes. The duration of the drug usage was determined by the attending physician and was up to 6 months. Reduxine®Met was prescribed in addition to the existing glucose-lowering therapy, the dose of metformin was adjusted to the patient's needs. Results: The “AVRORA” study was attended by 259 doctors and 5,812 patients in 240 medical institutions from 12 cities of the Russian Federation. The average age of patients was 46.6 ± 10.5 years, the ratio of male / female -24% / 76%. The decreasing of BMI during 6 months of the therapy amounted to 5.4 ± 2.3 kg / m2 (on average, 15.1 ± 6.4 kg). After 3 months of the therapy 81.6% of patients achieved clinically significant weight loss of 10.6% or more. The average decrease in waist circumference during 6 months of therapy was 13.8 ± 7.4 cm. A decrease of indicators of glycemic control and lipid metabolism right up to the target values was observed. Conclusions: In “AVRORA” study it was shown that addition of Reduxine®Met (sibutramine+ microcrystalline cellulose+metformine) to the complex therapy of the diabetes in combination with obesity according to approved indications is safe and effective for long-term treatment in regards to weight loss, regulation of lipemic index, glucose profile and quality of life.

Background: Despite the improvement in the quality of diabetes care in the Russian Federation (RF), coma remain one of the causes of death in patients with diabetes. Aim: To assess dynamic of epidemiological characteristic of acute complications in adult patients with T1D and T2D in 2013–16. Materials and methods: The database of the Russian Federal Diabetes register (81 regions). The indicators of coma for 2013–16 were estimated for 10000 adult patients with diabetes (>18 years). Results: In 2016, the prevalence of coma in RF was 225.9 with T1D and 11.6/10000 adults with T2D. For the period from 2007 the prevalence of ketoacidotic coma decrease three times in T1D, 4 times for T2D.Totally in 2016, 165 new cases of coma for both types of diabetes were registered, an average of 0.4/10000 adults. Interregional differences in the prevalence of coma were observed 0–4.2/10000 adults. The frequency of new cases of coma has a tendency to decrease: 0,9→0,4/10000 adults: T1D 5.7→3.4, T2D 0.6→0.2/10000 adults. When evaluating the structure of coma, redistribution is evident in their form. So in 2016 the proportion of hypoglycemic coma increased to 40.7%, and ketoacidotic coma decreased to 56.6% in T1D. With T2D, the difference expressed in a lesser degree. The mean duration of diabetes at the time of coma development increased with T1D from 3.8→9.1 years, with T2D 3.5→7.0 years. The maximum frequency of development of coma is recorded with the diabetes duration more than 30 years, regardless of the type. The patients’ age at the time of coma development in T1D increased to 27.5 years old, and in T2D it was 60.4 years, it didn’t change significantly. The assessment of glycemic control showed a significant improvement: a decrease in the proportion of patients with HbA1c≥ 9.0% (23% with T1D, 8.8% with T2D), an increase with HbA1c

Type 2 diabetes mellitus (T2DM) is a socially important disease with only symptomatic therapy developed due to lack of knowledge about its pathogenesis and underlying mechanism. Insulin resistance (IR) is the first link of T2DM pathogenesis and results in decrease of ability of insulin to stimulate glucose uptake by target cells. Development of IR involves genetic predisposition, excessive nutrition, stress, obesity or chronic inflammation due to disruption of insulin signaling within cells. Molecular mechanisms and markers of IR are characterized rather poorly, which prevents early diagnosis and creation of preventive therapy. Euglycemic clamp test is still a golden standard for IR diagnosis in clinic. Hyperglycemia is a distant consequence of IR in which damaging effect of oxidative and carbonyl stress is realized and diagnosis of T2DM is stipulated. Molecular chaperones and small heat-shock proteins have a protective effect at the early stages of T2DM pathogenesis, preventing development of reticulum stress and apoptosis. Endothelial dysfunction is related to T2DM and its cardiovascular complications, however, it is unknown on which stage of pathogenesis these changes occur and what are their molecular inductors. Finally, transcriptional activity and adipogenic differentiation play an important role in formation of new fat depots from predecessor cells and activation of brown and “beige” fat demonstrating hypolipidemic and hypoglycemic properties. The aim of this study was investigation of pathophysiological mechanisms of development of IR and endothelial dysfunction, role of transcription factor Prep1 and small heat shock proteins, evaluation of novel methods of diagnostics of IR and therapeutic potential of brown and “beige” fat, determination of biotargets for new antidiabetic drugs.

Background: Bone tissue is a non-classical endocrine organ, which produces at least two hormones: fibroblast growth factor 23 (FGF-23) and decarboxylated osteocalcin (OC). In addition to this, recent studies demonstrate that specific proteins involved in the paracrine regulation of bone remodelling can be measured in peripheral serum samples and may serve as additional biomarkers of bone metabolism. Aims: to evaluate the serum levels of biomarkers related to endocrine and paracrine function of bone tissue in patients with Cushing’s disease (CD) and acromegaly. Materials and methods: The study was conducted according to the cross-sectional case-control type. Fasting serum samples were taken between 8–10 a.m. from patients with CD, acromegaly and age-, sex- and BMI-matched healthy volunteers and stored at -40° C. Commercially available kits for enzyme-linked immunosorbent assay (ELISA) were used to determine the serum levels of FGF-23, co-factor (co-receptor) Klotho, cathepsin K, sclerostin, P1NP. Insulin-like growth factor-1 (IGF-1) was measured by the immunochemiluminescence assay, late-night (11 p.m.) salivary cortisol (LNSC) was evaluated using the electrochemiluminescence method. Non-parametric tests (the Kruskal-Wallis test and the Mann-Whitney test) were used to assess the differences between the groups of patients. Results: The study includes 78 patients, (37.6 years old, 95% CI 34.75–40.46): 29 patients with CD (group 1), 22 – with acromegaly (group 2), and 27 healthy individuals (group 3), matched by sex, age and BMI (p = 0.432, 0.373 and 0.725 between groups, respectively). LNSC in patients with CD and IGF-1 in patients with acromegaly were significantly higher compared to the control group (p = 0.004 and p

Background: Premature aging are frequently observed among individuals with type 1 diabetes. Decrease of ovarian reserve may be one of the characteristics of such process. Aims: To evaluate the ovarian reserve function in female patients of reproductive age with type 1 diabetes in comparison with healthy women. Materials and methods: This study evaluated 224 Caucasian women, age 18–37 years with type 1 diabetes and 230 healthy women of comparable age. Serum concentrations of anti-Mullerian hormone (AMH), inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and testosterone were compared on the 2–3 day of menstrual cycle as ovarian volume and antral follicle count (AFC). In addition, glycated hemoglobin level (HbA1c%) was evaluated. Results: We reveal statistically significant difference in following parameters in diabetic women in comparison with healthy women: AMH, AFC. But even in diabetic patients parameters remained within reference ranges. There was a pronounced negative relationship between the levels of HbA1c% and AMG. Conclusions: Ovarian reserve function parameters decrease in young women with type 1 diabetes in comparison with healthy women, but ovarian reserve parameters are in normal reference range. These findings are important in pregnancy planning consulting by gynecologists and endocrinologists. We must recommend to women with type 1 diabetes more early planning of natural pregnancy for treatment with reproductive technology in cases of prolog absence of nature pregnancy.

Background: Diabetic retinopathy (DR) is one of the most common causes of blindness in patients with diabetes mellitus (DM) that is why it’s 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 2013–16years. 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: 2,6–66,1%, 1,1–46,4%, respectively. The DR prevalence within 2013→2016 years was: T1 3830,9→3805,6; T2 1586,0→1497,0. Trend of new DR cases/per year increased: T1 153,2→187,8; T2 99,7→114,9. 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 9,6→13,1 years, T2 6,0→9,1. The prevalence of blindness tends to decrease: T1 92,3→90,8; T2 15,4→15,2/10.000 DM adults. The amount of new cases of blindness/per year increased: T1 4,3→4,6; T2 1,2→1,4. The mean age of blindness increased: T1 39,1→41,6 years, T2 64,4→67,4; the mean duration of diabetes before blindness occur (from the time of DM diagnosis) increased: T1 20,2→21,2 years, in T2 10,7→11,3. 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.

Congenital hypothyroidism is a heterogeneous group of diseases, which is manifested by loss of function of the thyroid gland that affects infants from birth. 8085% of cases are due to different types of thyroid dysgenesis. 5 genes have been described that are involved in the pathogenesis of thyroid dysgenesis: TSHR, PAX8, FOXE1, NKX2-1, NKX2-5. Aims. To evaluate the prevalence of mutations in the genes TSHR, PAX8, FOXE1, NKX2-1, NKX2-5 among patients with severe congenital hypothyroidism. Materials and methods. 161 patients (64 boys, 97 girls) with congenital hypothyroidism (TSH levels at neonatal screening or retesting greater than 90 mU/l) were included in the study. 138 subjects had different variants of thyroid dysgenesis, and 23 patients had normal volume of the gland. A next generation sequencing was used for molecular-genetic analysis. Sequencing was performed using PGM semiconductor sequencer (Ion Torrent, Life Technologies, USA) and a panel Hypothyroidism (Custom DNA Panel). Assessment of the pathogenicity of sequence variants were carried out according to the latest international guidelines (ACMG, 2015). Results. 13 patients had variants in thyroid dysgenesis genes (8,1%, 13/161): TSHR, n = 6; NKX2-1, n = 3; NKX2-5, n = 1; PAX8, n = 3; FOXE1, n = 0. Conclusions. Mutations in thyroid dysgenesis genes are a rare pathology. The majority of variants among our patients were identified in TSHR.

BACKGROUND: Chronic kidney disease (CKD) is one of the most severe complications of diabetes mellitus (DM), this determines the importance of the study of epidemiological characteristics of the disease. AIMS: To assess the epidemiological characteristics of CKD in adult DM patients with type 1 (T1), 2 (T2) in Russian Federation in 2013–16. METHODS: We have used the database of the Russian Federal Diabetes register, 81st regions included in online register. Indicators were estimated per 10,000 adult DM patients (>18years). RESULTS: In 2016, the CKD frequency registration was T1 23%, T2 6.9% with marked interregional differences 1.5-49.9%, 0.6–23.5%, respectively. The CKD prevalence in dynamics 2013→2016 was 2171.4→2303.0 in T1 and 512. →687.2 in T2. The incidence of new CKD cases increased 2 times in T1 (215.5 vs 104.2), and 3.7 times in T2 (190.4 vs 51.8). The analysis of distribution by CKD stages by KDIGO indicates the increase in the proportion of patients with low and moderate cardiovascular risk and end stage renal disease (ESRD) (with the initial stages of CKD, C1/2 A1) - 12.0→46.8% in T1; 10.0→50.4% in T2. The proportion of patients with a very high risk (stages C4/5 C3aA3 and C3bA2-3) progressively decreases: 13.4→6.7% in T1, 11.3→4.4% in T2. We observed relation between the CKD prevalence and DM duration. CKD develops in 5.1% patients if T130years; in T2 3.5% and 20.3%, respectively. The average age of CKD onset in T1 increased for 4,3yr (36,1→40,2), in T2 for 2,4yr (64,4→66,8), DM duration until CKD development increased in T1 11.8→14.2yr, in T2 7.6→8.2yr. CONCLUSIONS: There is a significant improvement in the quality of CKD diagnostics at the earlier stages, older age and a longer DM duration before CKD onset in both types while we observed the increasing trends in CKD prevalence in Russian Federation in the dynamics of 2013-2016. Advances in the management of patients with DM in recent years do not reduce the risk of CKD, but give us a delay in its development. The marked interregional differences frequency of registration of CKD might indicate some remaining problems in verification in a number of regions where the standard for mandatory assessment of albuminuria and glomerular filtration rate not implemented.

BACKGROUND: The enormous social lesion caused by high prevalence of diabetes mellitus (DM) determines the state importance of clinical and epidemiological monitoring organization. AIMS: To analyze epidemiological characteristics (prevalence, mortality, morbidity), the level of HbA1c, evaluate the therapy in Russian Federation in 2013–2017. METHODS: We have used the database of the Russian Federal Diabetes register – 81 regions included in the online register system. RESULTS: The total number of patients with DM was 4,498m. (3.06% RF population), including: Type 1 (T1) 5,7% (0,26 m), T2 92,1% (4,15m), other DM types 1,9% (83,8 ths). Distribution male/female: T1 53.5%/46.5%, T2 29%/71%, other DM types 24%/76%. The proportion of men decreases with aging. Number of patients >65 years was 2.293.520, including T1 21.97ths (3.6%), T2 2m271.5ths (54.7%). The prevalence 2013→2017 per 100,000 population was as follows: T1 159,8→169,6; T2 2455.3→2775.6; other DM types 51,2→65,8. Morbidity: T1 9,8→7,0; T2 226,7→185,2; other DM types 7,8→12,4. The structure of causes of death 2013→2017: T1: diabetic coma 2,0→1,5%, myocardial infarction 4,0→4,4%, cerebral circulation disorders 8,2→7,6%, cardiovascular insufficiency 18,5→16,4%, chronic renal failure 6,1→ 6,0%; T2 0,2→0,2%, 4,5→4,5%, 12,7→12,2%, 29,0→28,6%, 1,2→1,8%, respectively. Mortality: T1 2.3; T2 68.4, other DM types 0,8. Life expectancy (average age of death of patients): T1 male 50.3→50.2, female 60.2→ 57.2; T2 69.8→70.3, 75.1→75.9 respectively. The number of patients with target HbA1c level

BACKGROUND: The epidemiological study of diabetic foot (DF) is very important because of high risk lower limbs amputations in patients with diabetes mellitus (DM). AIMS: The aim of the study was to evaluate the DF prevalence in adult patients with type 1 (T1) and 2 (T2) diabetes in Russian Federation for period 2013–16years. METHODS: We have used the database of the Russian Federal Diabetes register, 81st regions included in the online register. Indicators were estimated per 10,000 adult DM patients (>18years). RESULTS: In 2016, the prevalence of DF in RF was T1 4,7%, T2 1,9%, with marked interregional differences: 0,15–19,9%, 0,07–10,3%, respectively. The DF prevalence in RF decreased: T1 506,3→473,6, T2 214,60→194,8. The incidence of new DF cases/per year was stable in adults with T1: 20,8→20,4/; increased in T2 13.2→14.2. The mean age of DF diagnosis increased by 2years for both DM types. The average DM duration of DF determine increased T1 15.4→19.0years, T2 7.4→10.1years. Proportion of DF forms: neuropathic with trophic ulcer 41.6%, neuropathic form (Charcot's foot) 17.9%, the neuroischemic 28.3%, ischemic 12.2%, in T2: 41.6%, 7,4%, 32,4%, 18,5%, respectively. The amount of new cases of amputations/per year in dynamics: T1 10,5→12,4, T2 9,6→10,9, with marked interregional differences 0.13–2.9% in T1, 0.04-6.0% in T2. The mean DM duration before amputation increased in T1 18.4→21.3years, in T2 9.1→9.9. The average amputation age: T1 51.7years, T2 66.2years. There was marked decrease in proportion of major amputations: T1 43,6→37,0%, T2 52.2→45.5 by redistribution in one toe amputations T14,0→10.0%, in T22,8→ 9.1%. CONCLUSIONS: The dynamic of new DF cases in adult patients in Russian Federation is stable at T1, in T2 tends to increase. The interregional differences in frequency of DF and amputations may be due to differences in the quality of specialized care, the lack or shortage of diabetic foot cabinets, treatment of patients with DF in general surgical practice in a number of regions, which is recognized as a less effective strategy. A positive fact that proportion of high amputations declines, DF develops in later age and longer diabetes duration, that may reflect the increasing effectiveness of preventive lower limbs in diabetes.

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumours, up to 40% of which occur in the setting of a hereditary syndrome. The incidence is 2 to 8 per million persons per year. The peak incidence occurs in the third to fifth decades of life. According to the most recent classification, chromaffin tumours refer to malignant neoplasms. The incidence of metastasis in pheochromocytomas is 10%; in paragangliomas it is 25%. Clinical manifestations of PPGLs are caused by the excess of catecholamines. More than 20 hereditary gene mutations are known to result in PPGLs development. According to the molecular and cellular pathophysiology, all currently known mutations can be divided into 2 groups: the first group SDHх, SDHAF2 (the assembly factor of SDH, FH, MDH2) disrupts the Krebs cycle and mitochondrial energy transport chain; the second group RET, NF1, TMEM127, MAX leads to mutations in receptor protein kinases (tyrosine kinase), activating intracellular signal pathways (PI3K-AKT-mTOR and MYC), which are responsible for cell growth, growth regulation and cell differentiation. As a result, HIF transcription factors are stabilized (oxidative stress), and DNA methylation is changed, which leads to severe disturbances in gene expression and to malignant transformations of cells. There are three main biochemical phenotypes of PPGLs: noradrenergic, adrenergic and dopaminergic. According to the tumor type, the patients age and family history, complementary genetic testing and molecular visualization are recommended. In clinical practice, the biochemical tumor phenotype, its stage, family history and especially the genetic tumor passport allow to choose the best molecular visualization method (SPECT-CT/PET-CT) to personalize treatment and prognosis.

The present review considers modern concepts of the physiological mechanisms of the formation of food behavior in a norm at several levels, beginning with the cellular level and ending with the level of functional systems. Neuroimaging methods used for both the study of the pathophysiological foundations of eating disorders and for determining the target for neurostimulation techniques are described. Methods of non-invasive brain stimulation such as transcranial magnetic stimulation and transcranial electrical stimulation, the mechanisms of their influence and aspects of safety of application are reviewed, the latest data on the results of studies on the use of the above methods in the therapy of obesity are summarized.

We do not recommend population screening for diabetes insipidus (DI) (B3). We recommend to perform diagnostic testing for central diabetes insipidus (CDI) in patients who underwent neurosurgery, after skull and brain trauma, subarchnoid hemorrhage (B3). We recommend excluding thirst impairment during all stages of diagnostic assessment (С3). We recommend excluding DI in cases of persistent hypotonic polyuria: excretion of more than 3 L. or more than 40 mL/kg of urine daily; urine osmolality less than 300 mOsm/kg or urinary specific gravity less than 1004 g/L in all urine samples or during Zimnitsky test (В3). After hypotonic polyuria is confirmed, we recommend excluding of the main causes of nephrogenic diabetes insipidus (NDI) (B3). We recommend simultaneous measurement of urine osmolality and blood osmolality/sodium level in order to confirm DI. Blood hyperosmolality (more than 300 mOsm/kg) and/or hypernatremia with low urine osmolality (less than 300 mOsm/kg) confirms DI (B2). If testing does not reveal these findings, we recommend performing a fluid deprivation test to exclude primary polydipsia (PP) (B2). Desmopressin test is recommended to distinguish CDI and NDI (B2). In cases of CDI we recommend to perform head MRI with contrast (B3). In cases of NDI we recommend assessing renal structure and function and possible electrolyte disturbances (C3). In cases of PP we recommend to refer a patient to psychiatrist (B3). We recommend treating CDI with synthetic vasopressin analogue – desmopressin (B1). We recommend an individual approach in choosing desmopressin dosage form (B2). As the initial dose is difficult to predict when starting desmopressin treatment, we recommend titrating the dosage using two approaches: “the average dose” and “as required” (C4). We recommend educating the patients to ensure knowledge of the features of various desmopressin dosage forms (C4). To decrease the risk of water intoxication, we recommend educating the patients to the water intake regimen adherence (С4). When CDI is accompanied by thirst impairment, we recommend titrating the dose in a clinical setting, with assessment of blood sodium, bodyweight and/or urine volume (C4).

The presented paper is a third revision of the clinical recommendations for the treatment of morbid obesity in adults. Morbid obesity is a condition with body mass index (BMI) ≥40 kg / m2 or a BMI ≥35 kg / m2 in the presence of serious complications associated with obesity. The recommendations provide data on the prevalence of obesity, its etiology and pathogenesis, as well as on associated complications. The necessary methods for laboratory and instrumental diagnosis of obesity are described in detail. In this revision of the recommendations, the staging of prescribing conservative and surgical methods for the treatment of obesity are determined. For the first time, a group of patients with obesity and type 2 diabetes mellitus is selected, in whom metabolic surgery allows a long-term improvement in the control of glycemia or remission of diabetes mellitus.

Department of pediatric surgery at the Endocrinology Research Centre has been around for nearly two years. During operation, surgical treatment has received more than 500 patients with various endocrine disorders. The article discusses modern diagnostic approaches and surgical options for diseases included in the new direction of pediatric surgery endocrine surgery in children. There are discussions about options for radical treatment of Graves disease in children, positive and negative aspects of surgical and radioactive iodine treatment. Is own stats of postoperative hyperparathyroidism. Is proposed to optimize the algorithm of actions in identifying thyroid nodules in children. In primary hyperparathyroidism, the emphasis is on the complexity of the postoperative management of patients related to the feature of childrens age in determining the severity of the reactions on the water-electrolyte disorders. Separately reviewed the literature of the adrenal glands diseases in children, demonstrating their own clinical cases which required surgical intervention. The authors describe the possibilities of modern neurosurgical equipment in the Endocrinology Research Centre in operations on the pituitary gland in children. Patients of different age groups performed transnasal transsphenoidal removal of tumors of the chiasm-sellar region using endoscopic assistance. The article also cited research data of pancreas diseases and their surgical treatment. Much attention is paid to the gender section of endocrine surgery in children. Discusses the tactics in disorders of sex development, gonadal tumors in children, diseases of the breast. In conclusion outlines the prospects for the development of endocrine surgery in children.

Hypogonadism in men, defined as a reduction in serum testosterone in combination with characteristic symptoms and/or signs (described in detail later), is common in diabetes mellitus (DM). These recommendations do not cover the whole range of pathologies that cause the development of testosterone deficiency (hypogonadism), but focus on its clinical variants and characteristic for men with diabetes. The recommendations provide data on the prevalence of hypogonadism in diabetes, its etiology. In the section "diagnostics" the features of anamnesis of patients with hypogonadism with diabetes, the necessary methods of physical and laboratory examination are presented in detail. The risk factors and clinical consequences of hypogonadism are separately examined. In the section "choice of treatment methods", there are possible treatment options for such patients using various androgenic therapies, taking into account the needs of the man, maintaining his reproductive function and risk factors. Particular attention is paid to indications, contraindications and risk factors for androgen therapy in men with diabetes, especially in old age. With this in mind, principles for monitoring the treatment are developed. Based on a large number of studies, favorable effects of androgen replacement therapy in men with hypogonadism and diabetes have been demonstrated.

Background: Cost-of-Illness Analysis (COI) constitutes the basis for the decision-making process on the budget and allocation in a modern health care system. Considering the wide prevalence of type 2 diabetes mellitus (Т2DM), it is important to perform COI in the Russian Federation (RF). Aim: The aim of the secondary objective FORSIGHT-Т2DM study was to conduct Cost-of-Illness Analysis (COI) of Т2DM in the Russian Federation in relation to taking into consideration the presence of complications and concomitant diseases. Materials and methods: COI of Т2DM was performed using the data obtained in Russian multicenter observational, pharmacoepidemiologic cross-sectional study of diabetes care for assessing routine healthcare pattern of T2DM in the Russian Federation (FORSIGHT-Т2DM). Information for each patient was collected from primary medical records and By asking patients to fill out a questionnaire. Total costs were calculated as the sum of direct medical costs (DCm), direct non-medical costs (DCn) and indirect costs (IC). Results: The final analysis included data from 2014 patients with T2DM residing in 45 cities of RF. Total direct medical costs (DCm) of treating Т2DM and its complications and comorbidities amounted to 105 337 rubles ($2742) per patient per year; direct non-medical costs (DCn) amounted to 24 518 rubles ($638) per patient per year; indirect costs (IC) amounted to 149 754 rubles ($3898) per patient per year. The total cost of T2DM in RF in 2014 year amounted to 279 609 rubles ($7278) per patient. The total cost of T2DM in RF in 2014 amounted to 279 609 rubles per patient. Conclusions: More than half (53,5%) of the total cost of T2DM is the loss of GDP due to patients’ disability. The DCm constitute 37,7% of the total cost of the disease, of which 57% is spent on treatment of T2DM complications and concomitant diseases, while only 10% is spent on glucose-lowering therapies.

Background. Diabetes mellitus (DM) is a non-infectious disease with a high prevalence worldwide and is one of the most common causes of diabetic kidney disease (DKD). Anaemia is a well-known complication of chronic kidney disease (CKD) and has been estimated to affect one in three adults with DM. Aims. To evaluate the prevalence and severity of anaemia among patients with DKD and to compare the distribution of anaemia among patients with diabetic and non-diabetic CKD. Methods. A total of 2,015 patients with DM [n = 807 with type 1 DM (T1DM); n = 1,208 with type 2 DM (T2DM)] and 244 patients with biopsy-proven chronic glomerulonephritis (CGN) were selected. Patients with glomerular filtration rate (GFR) of

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.

Currently, many AIP mutations responsible for the development of pituitary adenomas have been described. Penetence of pituitary adenomas in AIP-positive FIPA families is incomplete and varies widely. Data on the characteristics of metabolic changes in patients with familial pituitary adenomas associated with mutations in the AIP gene continues to be inadequate. Evaluation of the results of molecular genetic studies, as well as a thorough analysis of metabolic changes in these clinical cases, will help to develop and improve diagnostic and treatment algorithms, identify patient groups that require special attention of endocrinologists, timely screening, aggressive treatment, and careful dynamic observation.

Dear Colleagues! We are glad to present the 8th 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, 2017), American Association of Clinical Endocrinologists (AACE, 2017), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014) 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, EMPA-REG OUTCOME, 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 415 million patients by the end of 2015. According to the current estimation by the International Diabetes Federation, 642 million patients will be suffering from DM by 2040. These observations resulted in the UN Resolution on Diabetes 61/225 passed on 20.12.2006, and in 2011 - UN Political Declaration, addressed to national health systems, calling for the establishment of multidisciplinary strategy in the prevention and control of non-communicable diseases, where special attention is drawn to the problem of diabetes as one of the leading causes of disability and mortality. 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 4.35 million patients with DM in this country by the end of 2016 (3% of population) with 92% (4 million) – Type 2 DM, 6% (255 th) – Type 1 DM and 2% (75 th) – other types of DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 50% of Type 2 DM are diagnosed. So real prevalence of patients with DM in Russia is no less than 8-9 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. 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 Type 2 DM and its vascular complications, added information about bariatric surgery as a method of treatment of DM with morbide obesity. 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 DM. On behalf of the Working Group

Rationale. The rising incidence of type 2 diabetes mellitus (T2DM) allows researchers to conduct observational multicentre studies and obtain objective information about the epidemiology of diabetes and its complications and evaluate the efficacy of different therapies and diagnostic strategies designed to identify systemic vascular complications.Aims. To analyse epidemiological and socio-demographic parameters, the quality of glycaemic control, diagnostic monitoring and therapeutic measures typical among patients with T2DM living in Russian towns of different populations.Materials and methods. FORSIGHT-DM2 is an all-Russian multicentre observational epidemiological study that involves 2014 patients with T2DM from 45 different towns in the Russian Federation (RF). All patients have had T2DM for at least 1 year. They received glucose-lowering therapy and primary medical care from RF public outpatient health institutions between 01.01.2014 and 31.12.2014. For comparative analysis of the typical treatment for patients with T2DM, we stratified patients into groups based on the number of residents.Results. The data reveal a lack of glycaemic control (average НbА1с 7.9% ± 1.9%), with НbА1с > 8% in 36% of patients. The frequency of T2DM complications was high and the prevalence of retinopathy was 63.2%, nephropathy was 34.4% (7.8% had chronic kidney disease G3a-G5), peripheral polyneuropathy was 63.3%, ‘diabetic foot’ syndrome was 13.7% and osteoarthropathy was 5%. The number of T2DM-related complications is correlated with the HbA1c level and disease duration. Moreover, simultaneous influence of these factors led to a significant increase in the number of chronic complications associated with T2DM (r = 0.338 for T2DM duration, r = 0.262 for HbA1c; р < 0.001). Despite the high frequency of patient consultations with endocrinologists (83%) and a large percentage of hospitalisations in the current year (46%), the screening of chronic complications of T2DM in 2014 is insufficient.Conclusion. The results indicate insufficient glycaemic control among patients with T2DM and a higher prevalence of chronic complications compared with the national register of diabetic patients.

Background. Diabetes Mellitus Type 2 (DMT2) is a complex medical and social problem in the world and in the Russian Federation also due to prevalence and probability of cardio-vascular complications (CVC).Aim. Economic burden evaluation of DMT2 in the Russian Federation.Methods. Complex analysis of expenditures (direct and non-direct costs) based on epidemiological, pharmacoeconomics and clinical investigations, population and medical statistics data.Results. Calculated expenditures for DMT2 are 569 bln RUR per year, that is correspond to 1% of the Russian GDP, and 34,7% of that are expenditures for main CVC (ischemic heart disease, cardiac infarction, stroke). Main part of expenses are non-medical (losses GDP) due to temporary and permanent disability, untimely mortality – 426,7 bln RUR per year. Expenditures in estimated group of patients with non-diagnosed DMT2 but with already having CVC were at least 107 bln per year (18,8% from total cost). Relationship between cost of DMT2 and degree of it’s control was found in the Russian conditions. Estimated cost for compensated patient (HbA1c9,5%) was in 2,8 times higher due to more often main CVC in this group.Conclusion. DMT2 diagnosis improvement as well as effective treatment of early stages of illness can decrease probability of CVC and social economic expenditures.

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis.Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann–Whitney and Kruskal–Wallis tests. P-values

Aim. To determine the frequencies of alleles and genotypes of polymorphic marker rs7903146 of the TCF7L2 gene in latent autoimmune diabetes in adults (LADA) and healthy individuals. The aims of the study were also to compare the distribution of alleles and genotypes and to explore the association with the development of LADA.Materials and methods. A total of 96 patients (46 females and 50 males) with LADA and 201 healthy individuals were examined. A quantitative determination of autoantibodies GADA, ICA, IA-2A and ZnT8 in the serum of LADA patients was performed. All patients underwent genotyping of rs7903146 of the TCF7L2 genes.Results. There was an increased frequency of the T allele and genotype T+ of marker rs7903146 of the TCF7L2 gene in patients with LADA with low concentrations of autoantibodies compared to a group of patients with high concentrations and with controls. We observed significant associations of the T allele and genotype T+ with LADA in patients with low concentrations of autoantibodies [p = 0.02; odds ratio (OR) = 1.85; 95% confidence interval (CI) = 1.10–3.13 and p = 0.04; OR = 2.14; 95% CI = 1.01–4.53 for the T allele and genotype T+, respectively).Conclusion. The results of the study suggest that LADA patients with low concentrations of autoantibodies have a genetically pre-determined similarity with patients with type 2 diabetes.