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

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%)

Impact of Heat Resources on Rice Productivity in the Sarpinsky Lowland

The possibility of rice cultivation in the northern areas of rice sowing is determined by the sum of effective air temperatures (Σt ≥ 15 ∘C) over the growing season and its distribution over the vegetation phases of the plants. A long-term statistical and correlation analysis of rice productivity depending on the thermal resources of the Sarpinsky lowland at the Maliye Derbeta meteorological station for the period from 1964 to 2018 (correlation coefficient r = 0.68) is given. It is established that the sum of effective air temperatures varies from 3140.2 to 3999.7 ∘C, while the average annual value is 2820 ∘C. The highest yield (more than 5 t/ha) of rice grains is formed in years with the sum of effective temperatures over 3000 ∘C. The fluctuations of air temperature and their influence on the production process, and the yield of rice grains are analyzed, the results of which can be used as source data in modeling climate change scenarios and predicting rice grain production. The optimal amounts of effective air temperatures for the period April-September, ensuring the realization of the potential productivity of rice in the Sarpinsky lowland conditions, are determined

Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study

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