The use of long-acting insulin degludec in adult patients with type 2 diabetes mellitus in real clinical practice in Russia

BACKGROUND: Effective glycaemic control remains the most important task in managing the risks of Diabetes type 2 complications development. In this regard, the choice of insulin preparations with minimal variability of action is of utmost importance since this approach allows achieving the maximum treatment effectiveness and adequate safety level.AIM: The aim of this study was to investigate insulin degludec treatment effect on glycemic control in adult patients with Diabetes Mellitus (DM) type 2 in a real-world clinical setting in the Russian Federation.MATERIALS AND METHODS: The open prospective study was conducted in 2020–2021 in 35 clinical centers in 31 cities of the Russian Federation. The study included adult patients with type 2 DM treated according to Russian routine clinical practice. The prospective follow-up period was 26 weeks. The main study endpoints were changes in HbA1c level, fasting plasma glucose, insulin daily doses, number, and characteristics of different types of hypoglycaemia episodes and adverse events (AEs), and patient preferences compared to previous treatment.RESULTS: The study enrolled 494 patients. By the end of follow-up period:The mean HbA1c decrease was 1.6% (p<0.0001).Fasting plasma glucose level decreased by 3.4 mmol/L (p<0.0001).Daily basal and prandial insulin doses decreased by 1.6 IU/day (p<0.0001) and 2.1 IU/day (p<0.01), respectively.Severe episodes of hypoglycemia did not occur, while the incidence of nonsevere episodes decreased significantly.76 patients (15.4%) had 105 AEs, of which 41 (in 33 patients, 6.7%) were serious.COVID-19 was the most frequent AE reported in 21 patients (4.3%).Only in one case insulin degludec was withdrawn due to the patient’s pregnancy and the AEs that arose from it.Most patients (98.6%) preferred insulin degludec to previous treatment.CONCLUSION: The study demonstrated a statistically significant improvement in glycemic control, accompanied by basal insulin dose decrease combined with the absence of severe episodes of hypoglycemia, and significant decrease of nonsevere episodes (total and nocturnal). These results led to a large proportion of patients wanting to continue insulin degludec treatment preferring the medicine over previous treatment

Statistical Mechanics of Semi-Supervised Clustering in Sparse Graphs

We theoretically study semi-supervised clustering in sparse graphs in the presence of pairwise constraints on the cluster assignments of nodes. We focus on bi-cluster graphs, and study the impact of semi-supervision for varying constraint density and overlap between the clusters. Recent results for unsupervised clustering in sparse graphs indicate that there is a critical ratio of within-cluster and between-cluster connectivities below which clusters cannot be recovered with better than random accuracy. The goal of this paper is to examine the impact of pairwise constraints on the clustering accuracy. Our results suggests that the addition of constraints does not provide automatic improvement over the unsupervised case. When the density of the constraints is sufficiently small, their only impact is to shift the detection threshold while preserving the criticality. Conversely, if the density of (hard) constraints is above the percolation threshold, the criticality is suppressed and the detection threshold disappears.Comment: 8 pages, 4 figure

Transfer ionization and its sensitivity to the ground-state wave function

We present kinematically complete theoretical calculations and experiments for transfer ionization in H$^++$He collisions at 630 keV/u. Experiment and theory are compared on the most detailed level of fully differential cross sections in the momentum space. This allows us to unambiguously identify contributions from the shake-off and two-step-2 mechanisms of the reaction. It is shown that the simultaneous electron transfer and ionization is highly sensitive to the quality of a trial initial-state wave function

Long-term Follow-up of treatment of chronic foot wounds with recombinant human epidermal growth factor in patients with different complications of diabetes mellitus

BACKGROUND: Diabetic foot ulcer (DFU) is a dangerous complication of diabetes mellitus (DM), which can lead to the development of chronic wounds and amputations. Recombinant human epidermal growth factor (rhEGF) can be used as an adjuvant treatment for chronic wounds resistant to standard treatment. Studies have demonstrated its clinical efficacy, however, there is insufficient information on the long-term results of treatment, its safety and the effect on the progression of diabetes complications, adverse cardiovascular events and the development of cancer.AIM: To assess the long-term results of rhEGF therapy for trophic foot ulcers in individuals with multiple complications of diabetes.METHODS: The study included 20 patients with type 1 and type 2 diabetes and various forms of DFS without critical ischemia, who had previously been treated with DFS using rhEGF in order to assess the general condition, progression of microand macrovascular complications of diabetes, adverse cardiovascular events, the development of cancer and the quality of life.RESULTS: There was a statistically significant difference between the area of wound defects, the percentage of granulation tissue that filled the wound defect, before the start of rhEGF treatment and at the time of discharge from the hospital (p <0.05). During treatment with rhEGF, mild adverse events were observed in 35%. Complete epithelialization of wounds in most patients occurred in 3 [2; 4] months. In 11.76%, the wound was not completely epithelialized. Relapse occurred in 5.8% due to non-compliance with limb unloading. Minor amputation was performed in 1 patient. Progression of diabetic retinoand nephropathy was revealed in 23.5%. 11.76% suffered myocardial infarction of unknown age, 1 patient (5.88%) suffered acute cerebrovascular accident. Serious adverse events in the form of PE with a fatal outcome and critical ischemia of the lower limb were recorded in 5.8%.CONCLUSIONS: As a result of the study of long-term results of rhEGF treatment of chronic foot wounds, a low percentage of relapses and small amputations, the absence of high amputations and oncological diseases, the development of serious adverse events in 2 patients, the progression of diabetic retinoand nephropathy in 4 patients, the development of IM of unknown age in 2 patients was recorded. and stroke in 1 patient after rhEGF therapy

Practical aspects of initiation and use of SGLT2 inhibitors: inpatient and outpatient perspectives

In today`s therapy of type 2 diabetes mellitus, SGLT2 inhibitors have taken their rightful place both due to their positive hypoglycemic and outstanding cardiorenometabolic effects. Recent randomized clinical trials, such as DAPA HF, EMPEROR-Reduced and EMPEROR-Preserved, show the benefits of their use in the treatment of patients with chronic heart failure without regard to the status of type 2 diabetes mellitus and so significantly expands the range of use of SGLT2 in the practice of doctors of various specialties. This review presents not only the results of the most significant studies of SGLT2 inhibitors, but also the main approaches to the starting therapy with this class of drugs in various clinical situations, both inpatient and outpatient. In addition, potential adverse events and limitations associated with the use of SGLT2 inhibitors are discussed in detail, which must be taken into account when prescribing in particular patient. The practical aspects of SGLT2 inhibitors` prescription are considered separately through the prism of their safe use in the perioperative and postinfarction periods, as well as during other special conditions. Particular attention is paid to the monitoring of physical and general examination data and laboratory instrumental tests, the consideration of which will minimize adverse events and best benefit for many cardiological, endocrinological and nephrological patients

Effects of GLP-1RAs on cardiovascular outcomes in patients with type 2 diabetes mellitus: review of real-world data on target populations from diabetes registry in Russian Federation

RATIONALE. Over the past 20 years the prevalence of type 2 diabetes in Russia has more than doubled and reached 4.43 million people in 2020, while the growth rate keeps increasing. Most patients with T2DM are at a higher risk of developing major adverse cardiovascular events (MACE) associated with significant mortality. There is a strong evidence base that the drugs belonging to GLP-1RA class contribute to reducing the risk of cardiovascular events and renal outcomes. At the same time, the current prescribing rates of these treatments in Russia are quite low - only about 0.1% of patients are prescribed GLP-1RAs, according to Diabetes Registry data.AIM. Review the results of several randomized clinical trials (RCTs) concerning effects of GLP-1RA treatments on prevention of primary and secondary cardiovascular events and estimate the number of diabetic target population.MATERIALS AND METHODS. We examined the data from clinical trials on GLP-1RA treatments registered in Russia and used in routine clinical practice (ELIXA, EXSCEL, LEADER, SUSTAIN-6 and REWIND) and data from two meta-analyzes published as of December 1, 2020. The task was to evaluate the inclusion criteria, patient profile, and the clinical efficacy and safety profiles of  the studied therapies. Also, the analysis of clinical information from the Diabetes Registry (DR) was performed to estimate the number of target T2DM patients meeting RCTs inclusion criteria that could benefit from prescribing of GLP-1RAs.RESULTS. The reviewed clinical trials demonstrated a statistically significant reduction (p <0.05) in the risk of serious cardiovascular events in patients treated with Liraglutide [RR 0.87 (95% CI, 0.78-0.97)], Semagltuide [OP 0.74 (95% CI 0.58-0.95)] and Dulaglutide [RR 0.88 (95% CI 0.79-0.99)]. Meta-analyzes utilizing data from 6 RCTs with the total number of 56,004 T2DM patients, also, confirmed a statistically significant reduction in the risk of developing MACE (by 12%) in the studied population, and a 17% reduction in the risk of combined renal outcomes [RR 0.83 (95% CI 0.78-0.89), p <0.0001]. The DR patient population that met the RCTs inclusion criteria amounted to 538.6 thous. subjects in case of REWIND and 432.4 thous. in case of LEADER and SUSTAIN-6. The key differences between FDR patients and patients engaged in RCTs included gender and age characteristics. The DR patients were generally older and the bulk of them were women, which has to do with overall Russian demographic trends. The proportion of DR patients with established CVD was 26%, which closely matched the profile of patients from REWIND study (31.5%). According to DR data, the number of patients in whom the treatment was intensified following prescription of basal insulin was 7612 per year, which is close to a potential cohort eligible for alternative treatment with GLP-1RAs.CONCLUSION. All the drugs belonging to GLP-1RA class are clinically effective in reducing the risk of cardiovascular and renal outcomes, while demonstrating a favorable safety profile including with respect to lower risk of developing hypoglycemia. The decreased risk of complications was recorded both in patients with existing cardiovascular risks and patients with established CVD. Of all GLP-1RA treatments available in Russia at this point, the greatest clinical effectiveness is achieved by Liraglutide, Semaglutide and Dulaglutide. The estimated patient population from DR, meeting RCTs inclusion criteria and matching RCTs patient profile was over 500, 000 people with the largest number of patients meeting the REWIND criteria. The target population of patients with T2DM who may potentially benefit from the administration of GLP-1RAs is over 500, 000 people. Out of that number at least 7.5 thousand are patients, whose treatment is intensified following prescription of basal insulin (with an aim of improving glycemic control, but without consideration of cardiovascular risks).Currently, if we take the real world clinical setting in Russia, the number of patients receiving GLP-1RA treatments is substantially lower than the estimated figures (less than 1%), which requires reconsideration of the approach toward their prescribing as is recommended by state-of-the-art clinical guidelines prioritizing prevention of cardiovascular risks

Engineering current density over 5 kA mm-2 at 4.2 K, 14 T in thick film REBCO tapes

We report on remarkably high in-field performance at 4.2 K achieved in >4 μm thick rare earth barium copper oxide (REBCO) samples with Zr addition. Two different samples have been measured independently at Lawrence Berkeley National Laboratory and the National High Magnetic Field Laboratory, achieving critical current densities (J ) of 12.21 MA cm and 12.32 MA cm at 4.2 K, 14 T (), respectively, which corresponds to equivalent critical current (I ) values of 2247 and 2119 A/4 mm. These I values are about two times higher than the best reported performance of REBCO tapes to date and more than five times higher than the commercial HTS tapes reported in a recent study. The measured J values, with a pinning force of ∼1.7 T N m are almost identical to the highest value reported for thin (∼1 μm thick) REBCO at the field and temperature, but extended to very thick (>4 μm) films. This results in an engineering current density (J ) above 5 kA mm at 4.2 K, 14 T, which is more than five times higher than Nb Sn and nearly four times higher than the highest reported value of all superconductors other than REBCO at this field and temperature. The reported results have been achieved by utilizing an advanced metal organic chemical vapor deposition system. This study demonstrates the remarkable level of in-field performance achievable with REBCO conductors at 4.2 K and strong potential for high-field magnet applications. c c c c e 3 -2 -2 -3 -

Conductance distribution between Hall plateaus

Mesoscopic fluctuations of two-port conductance and four-port resistance between Hall plateaus are studied within a realistic model for a two-dimensional electron gas in a perpendicular magnetic field and a smooth disordered potential. The two-port conductance distribution $P(g)$ is concave between $g=0$ and $g=1$ and is nearly flat between $g=0.2$ and $g=0.8$. These characteristics are consistent with recent observations. The distribution is found to be sharply peaked near the end-points $g=0$ and $g=1$. The distribution functions for the three independent resistances in a four-port Hall bar geometry are, on the other hand, characterized by a central peak and a relatively large width.Comment: 11 pages, 5 ps figures, submitted to Phys. Rev.