Epidemiology of acute diabetes complications (coma) according to the Federal Diabetes register of the Russian Federation (2013–2016)

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 <7% (32.4% and 51.7%, respectively). The average value of HbA1c in 2016 with T1D – 8.21%, with T2D – 7.48%. Conclusions: It is established that the dynamics of the frequency of development of coma in 2013–16 in adult patients with diabetes in the RF has a stable tendency to decrease: 1.5 times with T1D and more than 3 times with T2D. It can be assumed that this is due to the improvement in the quality of diabetes care and glycemic control in general, as well as the use of modern medicines. Attention is required to draw to the high frequency of coma in T1D, the development of coma with a longer duration of diabetes, an increase in the proportion of patients with hypoglycemic coma. Significant interregional differences in the frequency of coma registration require additional analysis

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

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Grou

Insulin resistance and its possible personal stress moderators

Background. Recently, insulin resistance (IR) has been actively investigated by experts in various fields. Here we aim to study the effect of stress on the development of IR. Objective. To study the associations between IR and personal stress moderators (self-attitude, locus of control and coping strategies) as well as the related performance lifestyles. Methods. The study included 63 patients (16 men; mean age, 48.2 11.7 years). Of these participants, 26 were diagnosed with type 2 diabetes mellitus, 10 with impaired glucose tolerance, 6 with impaired fasting glucose and 21 with normal glucose tolerance. The levels of HbA1c and IR ratio were determined using HOMA. Well-known psychological assessment questionnaires were used to assess the effect of personal stress moderators. Results. There was a significant relationship between IR and personal stress moderators. A positive self-attitude was associated with a lower risk of IR (p 0.05), which can be explained by a decrease in the risk of developing stress. Assertive coping strategies were most pronounced in subjects with a low level of IR (p 0.05). Personal characteristics also determined an individuals lifestyle, which may have an impact on the increase in IR. There was an association between high levels of IR and unhealthy alimentary preferences (p 0.05). Such preferences were also associated with personal characteristics, such as external locus of control, less positive self-attitude and passive coping strategies (p 0.05). People with high IR rarely engage in a regular physical activity; there was a direct correlation between the frequency of physical activity and assertive coping strategies (p 0.01). Married participants had high levels of IR (p 0.05). Conclusion. There were significant relationships between IR and personal stress moderators, such as self-attitude and coping strategies. Besides the direct effects on stress levels, personality traits may also indirectly increase the risk of IR by influencing the individuals lifestyle. There is a need to investigate the fact that married people have higher levels of IR

Cannabinoid CB2 Receptors in a Mouse Model of Aβ Amyloidosis: Immunohistochemical Analysis and Suitability as a PET Biomarker of Neuroinflammation.

In Alzheimer's disease (AD), one of the early responses to Aβ amyloidosis is recruitment of microglia to areas of new plaque. Microglial receptors such as cannabinoid receptor 2 (CB2) might be a suitable target for development of PET radiotracers that could serve as imaging biomarkers of Aβ-induced neuroinflammation. Mouse models of amyloidosis (J20APPswe/ind and APPswe/PS1ΔE9) were used to investigate the cellular distribution of CB2 receptors. Specificity of CB2 antibody (H60) was confirmed using J20APPswe/ind mice lacking CB2 receptors. APPswe/PS1ΔE9 mice were used in small animal PET with a CB2-targeting radiotracer, [11C]A836339. These studies revealed increased binding of [11C]A836339 in amyloid-bearing mice. Specificity of the PET signal was confirmed in a blockade study with a specific CB2 antagonist, AM630. Confocal microscopy revealed that CB2-receptor immunoreactivity was associated with astroglial (GFAP) and, predominantly, microglial (CD68) markers. CB2 receptors were observed, in particular, in microglial processes forming engulfment synapses with Aβ plaques. In contrast to glial cells, neuron (NeuN)-derived CB2 signal was equal between amyloid-bearing and control mice. The pattern of neuronal CB2 staining in amyloid-bearing mice was similar to that in human cases of AD. The data collected in this study indicate that Aβ amyloidosis without concomitant tau pathology is sufficient to activate CB2 receptors that are suitable as an imaging biomarker of neuroinflammation. The main source of enhanced CB2 PET binding in amyloid-bearing mice is increased CB2 immunoreactivity in activated microglia. The presence of CB2 immunoreactivity in neurons does not likely contribute to the enhanced CB2 PET signal in amyloid-bearing mice due to a lack of significant neuronal loss in this model. However, significant loss of neurons as seen at late stages of AD might decrease the CB2 PET signal due to loss of neuronally-derived CB2. Thus this study in mouse models of AD indicates that a CB2-specific radiotracer can be used as a biomarker of neuroinflammation in the early preclinical stages of AD, when no significant neuronal loss has yet developed

CB2 receptors are expressed in microglial cells and do not accumulate in Aβ plaques of APPswe/PS1ΔE9 mice.

<p>A representative confocal image of staining for CB2 receptors (green, H60 antibody) in the cortex of 12 mo-old transgenic mice. (B) An overlap of red (CD68) and blue (DAPI) channels for the image shown in A. Note a characteristic gathering of activated microglia around an amyloid plaque (marked by an asterisk). (C) An overlap of channels shown in A-B. Note that areas with high CB2 intensities overlap with CD68-positive areas. White rectangle shows an example of areas used for quantifications presented in E-F. Scale bar is 15 μm. (D) Quantification of CB2 densities (integrated intensities/area) in CD68-positive and –negative areas. 26 areas like that shown in A-C were used for the quantification (n = 2 transgenic mice). Asterisk indicates a significant difference between CD68+ and CD68- areas (one-way ANOVA, p<0.0001). (E) A scatterplot of CB2 and DAPI intensities as a function of distance from the center of an Aβ plaque with radius ~10 μm. Note low CB2 signal in the core of the plaque. CB2 and DAPI intensities were normalized (%) to a maximum signal on each channel. An example of an area used for calculations is shown by a white rectangle in C. (F) Quantification of CB2 signal at different distances from a plaque center. 4–6 slices of z stacks from five plaques (range of radiuses 7–15 μm) were used in one-way ANOVA. Asterisks indicate a significant increase (p<0.0001, post-hoc test) in CB2 intensities as compared to the core of plaques (radius ≤ 7 μm).</p

SUV brain PET of [¹¹C]A836339 in two AD mice (APPswe/PS1ΔE9) in baseline and blockade experiments with AM-630 (2 mg/kg, s.c.), a selective CB2 inverse agonist.

<p>12 mo-old male mice were used in this study. (A) Whole brain time-uptake curves. Insert: averaged SUV values (2–10 min). Red–baseline; black–blockade. (B) Sagittal baseline (top) and blockade (bottom) images (2–10 min). This study demonstrates that in vivo binding of [^<b>11</b>C]A836339 in AD mice is specifically mediated by CB2 receptors that is consistent with our previous [^<b>11</b>C]A836339 ex vivo studies in AD mice [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129618#pone.0129618.ref021" target="_blank">21</a>].</p

Comparison of CB2 immunoreactivity in neurons, activated microglia and astrocytes.

<p>(A) Representative confocal images from the cortex of 12 mo-old non-transgenic (NTG) and APPswe/PS1ΔE9 transgenic (AD) mice stained with a CB2 receptor antibody (H60sc; left columns; green) and markers for neurons (NeuN, far red), activated microglia (CD68, red), and astrocytes (GFAP, far red). Brain slides were counterstained with DAPI shown with a grey pseudo color. Note substantial micro- and astro-gliosis in the cortex of the AD mouse brain. In the NTG mice, CD68+ and/or GFAP+ areas were rare (indicated in the upper right panel by an arrowhead and arrow, respectively). (B) Quantification of densities (+-SEM) for CB2 receptor immunoreactivity (integrated intensities/area) in areas positive for NeuN, CD68, and GFAP markers. Densities were averaged over 22 (AD) and 14 (NTG) images of the cortex as shown in A (n = 2 mice per genotype). Single and double asterisks indicate a significant difference between NTG and AD groups as a result of LSD post-hoc test with p levels <0.01 and 0.0001, respectively. Arcs indicate non-significant (NS) differences. Single and double pound signs (p levels <0.05 and 0.001) indicate markers that correspond to the highest CB2 density in the NTG (blue sign) or AD (red sign) groups (LSD post-hoc test). Solid black line at the level of 4,930 shows average densities for the background. (C) An example of NeuN (blue), CD68 (red), and GFAP (green) masks from the AD image shown in A. NeuN masks were drawn by hand as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129618#pone.0129618.g002" target="_blank">Fig 2C</a>; masks for CD68 and GFAP were created by a threshold function. Black area represents background. Scale is 15 μm.</p

CB2 immunoreactivity in neurons of the cortex and motor trigeminal nucleus of 12 mo-old APPswe/PS1ΔE9 transgenic mice.

<p>Representative confocal images of cortical neurons (upper panels) and neurons of the motor trigeminal nucleus (lower panels) with double immunostaining using NeuN (green; A) and CB2 R (red, H60: B) primary antibodies. Scale is 15 μm. C. Example of neuronal bodies visualized by NeuN (green). The neuron outlines were transferred to CB2 channel (red). Note cytoplasmic granules (pseudo-yellow) with autofluorescence visible on DAPI channel (not shown). The areas occupied by such granules were not considered in the analyses of CB2 immunoreactivity. Scale is 5 μm. D. Quantification of CB2 densities (integrated intensities/area) in NeuN-positive and –negative areas. Signal intensities were averaged across 30 non-overlapping fields (n = 2 mice). * and ** indicate significant differences in CB2 signal between NeuN-positive areas and background, p<0.01 and 0.001, respectively (ANOVA).</p

Distribution of SARS-CоV-2 seroprevalence among residents of the Tyumen Region during the COVID-19 epidemic period. Journal of microbiology, epidemiology and immunobiology

Introduction. In late 2019 - early 2020, an outbreak of infection caused by a novel strain of beta coronavirus SARS-CoV-2 was reported. The World Health Organization defined the disease as coronavirus disease 2019 (COVID-19). In the Tyumen Region, the first case of COVID-19 was diagnosed on 31/1/2020. The source of infection was a female student who came from Jinan, Shandong province (China). The number and rate of cases were steadily increasing from the 16th week through 28th week in 2020. The highest rate was 36.87 cases per 100 thousand people. Afterwards, the cumulative incidence kept increasing gradually, but not as quickly.The purpose of the seroepidemiological study was to measure the level and to identify the structure of herd immunity against the SARS-CoV-2 virus among the population of the Tyumen Region during the rapid spread of the COVID-19 outbreak.Materials and methods. Volunteers for participation in the study were selected through questionnaire surveys and random sampling. The exclusion criterion was an active COVID-19 infection at the time of the survey. A total of 2,758 individuals were tested for SARS-CoV-2 specific antibodies. The age of the surveyed volunteers ranged from 1 year to 70 years and older.Results of the study. During the active phase of the COVID-19 incidence, the population of the Tyumen Region showed moderate (24.5%) seroprevalence of SARS-CoV-2. At the same time, the tests revealed a high (97.8%) rate of asymptomatic infection cases in seropositive individuals who had never been diagnosed with COVID-19 and did not have history of positive PCR test results or acute respiratory infection symptoms on the day of testing. The maximum level of herd immunity was identified in children aged 1-6 years (34.7%), which was significantly higher compared to the average level of seroprevalence in the entire cohort. In recovered COVID-19 patients, antibodies were detected in 68.2%. In individuals with positive PCR test results, antibodies were detected in 64%. Conclusion. The results of the assessment of the level of herd immunity against the SARS-CoV-2 virus are crucial for prediction of the development trend of the epidemic and for planning specific and non-specific COVID-19 prevention measures