In memory of Alexander Y. Mayorov (November 16, 1964 – January 1, 2023)

On January 1, 2023, Head of the Diabetes Prediction and Innovation Department of the Endocrinology Research Centre, the leader of the public patient organization «Russian Diabetes Association», Doctor of Medical Sciences, Professor ­Alexander Mayorov, died at the age of 59

On the centenary of the insulin discovery

The discovery of insulin and the beginning of its use in 1921–1922 made a revolution in endocrinology and in medicine in general. This significant event gave millions of patients with diabetes not only the opportunity to live, but also the hope that their life with this disease would be full.The article examines the history of insulin discovery, as well as the evolution of several generations of insulin preparations and the advantages of each of the generations that have radically changed not only life expectancy, but also its quality.The first generation — insulins of animal origin and the solution of the first tasks of their sufficient production and purification. The next generation is human insulins, the purification of which was also a problem. The third generation is insulin analogues, the action of which became closer to the action profile of natural insulin. And the last generation — insulin analogues, most closely mimicking the action of endogenous insulin.Along with the development of insulin preparations, the article traces the evolution of the devices of its administration

Towards prevention of type 1 diabetes: FDA approved first drug with potential to delay clinical stage of disease

Given the increased morbidity and mortality in patients with type 1 diabetes mellitus (T1DM), as well as the burden posed by the disease, the search for methods to prevent the destruction of beta cells is of paramount importance. Until recently, no attempts of immunotherapeutic interventions have achieved significant success, allowing at best reducing the rate of destruction of beta cells without stopping the immune process and not allowing normalization of glycemia. In November 2022, the U.S. Food and Drug Administration (FDA) approved the drug teplizumab to delay clinical diagnosis of T1DM. The purpose of the publication is to evaluate the results of teplizumab treatment in high-risk participants with the second (preclinical) stage of T1DM, as well as to consider further prospects for this treatment

Rational approach to patients treatment with type 2 diabetes and obesity: results of the All-Russian observational program «AURORA»

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

Comparative Analysis of Clinical, Hormonal and Morphological Studies in Patients with Neuroendocrine ACTH-Producing Tumours

This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas

Lack of association between genetic markers on chromosome 16q22-Q24 and type 1 diabetes in Russian affected families

Aim To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients. Method Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.1 software. Four microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally tested for association with T1D in 114 simplex families, using transmission disequilibrium test (TDT). Results A peak of linkage (MLS = 1.35, NPL = 0.91) was shown for marker D16S750, but this was not significant (P = 0.18). The subsequent linkage analysis in the subset of 46 multiplex families carrying a common risk HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22, respectively, but showed no significant linkage (P = 0.11) to T1D in the 16q22-q24 genomic region. TDT analysis failed to find significant association between these markers and disease, even after the conditioning for the predisposing HLA-DR4 haplotype. Conclusion Our results did not support the evidence for the susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data set. The lack of association could reflect genetic heterogeneity of type 1 diabetes in diverse ethnic groups

Course and treatment of diabetes mellitus in the context of COVID-19

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

Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register data of 01.01.2021

BACKGROUND. One of the priority directions in the development of the health care system is to reduce the medical and social damage caused by the increase in the prevalence of diabetes mellitus (DM). From this point of view, the development of a diabetes register is very important as the main information and analytical platform for clinical and epidemiological monitoring of diabetes in the Russian Federation (RF).AIMS. The aim of our study was to analyze a dynamic (2016–2020) of the epidemiological characteristics of diabetes mellitus in the Russian Federation (prevalence, morbidity, mortality), the prevalence of complications, the level of HbA1c and the dynamics of the structure of glucose-lowering therapy (GLT) according to the Federal Diabetes Register (FDR).MATERIALS AND METHODs. The database of FRD (http://diaregistry.ru) 84 regions of the RF. The data are presented in dynamics 2016→2020.RESULTS. The total number of DM patients in the RF as of 01.01.2021 was 4,799,552 (3.23% of the population), including: Type 1 (T1) — 5.5% (265.4 ths) , T2 — 92.5% (4.43 million), other DM types — 2.0% (99.3 ths). The dynamics of prevalence was 168.7→180.9/100 ths people with T1, and 2709 → 3022/100 ths people with T2; morbidity in T1 10.5→7.7/100 ths population, in T2 219.6→154.2/100 ths population. Age and sex characteristics: the proportion of men in T1 — 54%, in T2 — 30%; the max proportion of patients with T1 at the age of 30–39 years, T2 65–69 years. Mortality: T1 3.0 → 2.7/100 ths population, T2 87.7→93.9/100 ths of the population, the main cause of death was cardiovascular: in T1 38,1% cases, in T2 — 52,0%. Life expectancy (average age of death of patients): T1 was 53.2years, the dynamics in males 50.7 → 50.5years, ­females 58.7→55.2years; in T2 — 73.5 years, males 70.2→70.1years, females 75.7→75.4 years. The dynamic of DM duration until the death: in T1 17.4→19.0 years; in T2 11→11.4 years. The incidence of diabetic complications in T1 and T2 patients: neuropathy 43.3% and 24.4%, nephropathy (CKD) 25.9% and 18.4%, retinopathy 31.7% and 13.5%, respectively. The ­proportion of ­patients with HbA1c <7%: in T1 32.3%→36.9%, in T2 51.9%→52.1%, with HbA1c ≥ 9.0% in T1 23.1%→18.7% , in T2 8.9%→8.0%. The structure GLT in T2 patients: glucose lowering medications (GLM) — 76.2% (monotherapy — 44.1%; ­combination of  2 GLM — 28.9%, 3 GLM — 3.2%), insulin therapy in 18,8%, without drug therapy in 4.9%.CONCLUSIONS. The performed analysis demonstrates the importance of dynamic assessment of epidemiological characteristics and monitoring of clinical data on patients with diabetes through a registry for assessing the quality of diabetes care and the prospects for its development

Obesity with and without type 2 diabetes: are there differences in obesity history, lifestyle factors or concomitant pathology?

Background: Obesity is one of the most significant risk factors for type 2 diabetes (T2D), but a large number of patients with morbid obesity maintain normal glycemia for a long time. There are no definite easy-to-measure clinical features that distinguish severely obese people who will or will not develop T2D. These features may be useful in clinical practice to predict T2D development in obese patients.Aims: We aimed to identify clinical features (lifestyle factors, obesity history, concomitant diseases) that may be associated with T2D in obese patients.Materials and methods: The study was conducted at single center during 2002 and 2017 and recruited patients with BMI≥30 kg/m2 who attended bariatric surgeon. Patients weight and height were assessed by the doctor, other features were obtained from the questionnaire: overweight and obesity history (age of onset, duration, family history of obesity), lifestyle factors, T2D and concomitant diseases medical history. Patients were divided into 2 groups with regard to the presence of T2D. Data analysis was performed with Statistica 13.3.Results: The study included 170 patients with known T2D and 528 patients without history of T2D and prediabetes. Both groups had similar gender structure, as well as current and peak BMI. There were no significant differences in overweight/obesity duration, obesity family history, lifestyle factors and smoking status of patients. Obese patients without T2D were younger than T2D patients at the time of T2D onset (median age 40 and 45 years respectively). Patients without T2D started to gain weight earlier than those with T2D (median age 17 and 25 years respectively) and reached their peak BMI during 1 year before study entry, while patients with T2D went through maximum weight previously. The frequencies of concomitant diseases didn’t differ between the groups with the exception of hypertension that started later in patients with T2D (median age 51 and 47 years in patients with and without T2D respectively); also patients with T2D had gastroesophageal reflux disease (GERD) and chronic back pain less often than patients without T2D with regard to age.Conclusions: Clinical features that distinguished obese patients with and without T2D were age at the start of overweight/ obesity and concomitant disease profile (hypertension, GERD, chronic back pain) at corresponding age

Plasma dynamic synthesis of ultradispersed copper oxides

Copper oxide is necessary material for production of superconductors. The issue of obtaining high purity and nanosides CuO is actual. This article shows the results on the obtaining of nanodispersed copper oxide by plasma dynamic method in system based on coaxial magneto plasma accelerator with copper electrodes. Such analyses of ultradispersed synthesized products as X-Ray diffractometry, IR-spectroscopy and thermal analysis were carried out. According to XRD such phases as copper Cu, copper oxide (I) Cu[2]O, copper oxide (II) CuO, and copper hydroxide hydrate Cu(OH)[2]xH[2]O were identified in the product. It was found that with the gradual heating of the initial product up to 800°С the phase content changed dramatically in terms of enhancing copper oxide phase (up to 97%)