High level of glycated hemoglobin (HbA_1c) in patients with COVID-19 is a marker of the severity of the infection but not an indicator of previous diabetes mellitus

BACKGROUND: Less than a year has passed since the start of the new coronavirus infection COVID-19 pandemic caused by SARS-CoV-2. First published research results demonstrate a frequent increase in glycemia in patients without previously diagnosed carbohydrate metabolism disorders. A possible relationship between the carbohydrate metabolism state and the course of COVID-19 is considered.AIM: To identify the incidence of known and newly diagnosed diabetes mellitus (DM) in hospitalized patients with COVID-19 and evaluate the relationship between glycated hemoglobin (HbA1c), inflammation markers and infectious disease severity.METHODS: A single-center, cross-sectional, retrospective study included 155 patients with confirmed COVID-19 and bi- lateral polysegmental viral pneumonia hospitalized in the Endocrinology Research Centre, Russian Federation. Diagnosis of carbohydrate metabolism disorders was based on the HbA1c level, blood glucose level at admission (BGA) and fasting plasma glucose (FPG). Patients were divided into 2 groups: without the previously diagnosed DM (n=129, 83.3%) and with known history of DM (n=26, 16,7%). Patients without previously diagnosed DM were divided into subgroups according to HbA1c levels: ≤6,0% (Group A), >6,0% HbA1c, <6.5% (Group B), ≥6,5% (Group C). Additionally, insulin, interleukin 6 (IL-6) and D-dimer levels were measured in all patients. Blood oxygen saturation (SpO2) was measured by pulsoximetry, computerized tomography of lungs with calculation of lung parenchyma damage percentage.RESULTS: Type 2 DM was previously established in 16.7% of all included patients. Among patients without DM history, DM was revealed in 8 patients (5.2%), based on HbA1c, FPG and BGA. In 66 patients (42.6%) we observed no changes in carbohydrate metabolism. In 55 patients, the interpretation of carbohydrate metabolism state was difficult due to inconsistency of HbA1c level with FPG and BGA: in particular, the level of HbA1c ≥ 6.5% (which corresponds to the diagnostic threshold of the DM) was detected in 19 patients (12,2%) with normal FPG and BGA. No true stress hyperglycemia on admission and according to FPG was reported. Despite the presence of confirmed DM, HbA1c levels positively correlated with inflammatory markers (erythro- cyte sedimentation rate, C-reactive protein, IL-6) and SpO2. Patients with a HbA1c ≥6.5% without DM history had the most severe course of the disease: longest duration of hospitalization, largest damage of the pulmonary tissue, and high lethality.CONCLUSION: The incidence of DM among patients hospitalized with COVID-19 was 21.9% (16.7% had previous diagnosis of DM, 5.2% — newly diagnosed), which is 1.5 times higher than in general population in a comparable age category. It is difficult to assess the carbohydrate metabolism disorders in patients in acute infectious period. An increased level of HbA1c (≥6.5%), first detected in the acute period of infection, in combination with normal FPG and BGA parameters, cannot be a diagnostic criterion and requires dynamic monitoring. HbA1c level can be considered as a predictive factor of COVID-19 severity, independent of DM

Time-related OCT-A changes in preclinical retinopathy and their association with systemic factors

Background. Optical coherence tomography angiography (OCT-A) is a promising tool for the detection of microvascular impairment at the preclinical stage of diabetic retinopathy (DR). Evaluation of dynamic OCT-A changes and their association with systemic factors can help to reveal early biomarkers of DR progression.Aim: to evaluate time-related OCT-A changes and their association with systemic factors in type 1 diabetes mellitus (DM1) patients with no apparent DRMaterials and methods. 38 DM1 patients with no apparent DR and 39 healthy volunteers were included in the study. All participants underwent 7-fi eld fundus photography, OCT and OCT-A. We analyzed OCT-A parameters (foveal avascular zone (FAZ) area (mm2), acircularity index (AI), vessel density (VD), skeletonized density (SD)) as well as the results of blood and urea tests.Results. After one year of observation, AI was significantly higher (р = 0.005) and VD0–300 was signifi cantly lower in superfi cial vascular plexus (SVP, p < 0.0001) and deep capillary plexus (DCP, р = 0.032) in DM1 patients. We have also registered a positive correlation between AI and triglycerides (TG) level (r = 0.627, p = 0.007) as well as a negative correlation between ketones and VD (SVP VD0–300: r = –0.695, p = 0.030; intermediate capillary plexus (ICP, VD0–300: r = –0.551, p = 0.041; DCP, VD0–300: r = –0.704, p = 0.003; SVP, VD300–600: r = –0.853, p = 0.001).Conclusions. After one year of observation, we have registered an increase in AI level and a decline in VD in SVP and DCP which can be the earliest signs of DR progression. A signifi cant correlation between these parameters and systemic factors indicates their role as potential DR biomarkers

STEREOFUNCTIONAL FEATURES OF MOTHER-PLACENTA-FETUS SYSTEM IN OPTIMIZATION OF COMPLEX TREATMENT OF THREATENING PRETERM LABOR

Purpose: improving the efficiency of complex treatment of threatened abortion.Materials and Methods: The study involved 299 primigravidas. The I clinical group consisted of 78 women with threatened miscarriage receiving combination therapy (standard medication and acupuncture). The II clinical group consisted of 76 women receiving combined medication and acupuncture to our improved method. In the III clinical group - 71 women with threatened miscarriage, which received only standard medical therapy. In the IV (control group) there were 74 pregnant women with physiological pregnancy.Results: It has been proven that the lateral stimulation of biologically active points of acupuncture taking into account the factor of placental laterality in the utero-placental-fetal complex initiate functional processes accompanied by an increase right asymmetry of utero-placental blood flow and uterine activity, and improvement of the fetus condition.Summary: We proved that in unilateral acupuncture impact to the placenta, processes of functional symmetry in the utero-placental-fetal complex in women with threatened termination of pregnancy are replaced by functional asymmetry of processes that improve the condition of the fetu

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

Early functional and microcirculatory changes in patients with type 1 diabetes mellitus and no apparent diabetic retinopathy

BACKGROUND: Diabetic retinopathy (DR) is the leading complication of diabetes mellitus (DM) which is reported to affect more than one-third of the global diabetic population. Optical coherence tomography angiography (OCT-A) can help to reveal early biomarkers of DR to improve current diagnostic approach.AIMS: To evaluate early visual functions deficiency and OCT-A changes in patients with type 1 DM (T1DM) without clinical signs of DR.MATERIALS AND METHODS. 74 eyes of 40 T1DM patients with no apparent DR and 49 eyes of 28 healthy volunteers were included in the study. The mean duration of DM was 11,7 ± 6,1 years. All participants underwent standard ophthalmological examination, low-luminance visual acuity (LLVA) assessment, 7-field fundus photography, OCT and OCT-A. We analyzed LLVA deficit as a marker of visual function. For OCT-A scans we evaluated foveal avascular zone (FAZ) area (mm2), acircularity index (AI), vessel density (VD), skeletonized density (SD) and vessel diameter index (VDI) in superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP).RESULTS: LLVA deficit was significantly higher in T1DM patients (0,16±0,05 vs 0,10±0,04, p<0,0001). We also detected a significant difference in AI level (11,47 ± 0,24 vs 1,31 ± 0,15, p<0,0001). VD was significantly lower in T1DM patients in SVP (25,37 ± 2,24%, vs 26,67 ± 1,81%, p=0,028) and DCP (17,22 ± 3,10 % vs 18,29 ± 1,95%, p=0,015)CONCLUSIONS: Our results demonstrate early visual functions deficiency and OCT-A changes at the preclinical stage of DR. The prognostic value of these findings will be studied during longitudinal observation

Seasonal periodicity of melatonin exchange and hormonal status of pregnant women in dependence on fetus sex

Objective: to study melatonin metabolism and hormonal status of pregnant women in different seasons of the year, depending on the sex of the fetus. Materials and methods: 538 women were examined at the time of physiological gestation of 37-40 weeks. The first group — 286 pregnant women with female fetuses and the second group — 254 pregnant with male fetuses. Estimation of the hormonal status included the determination of the level of cortisol, estradiol, adrenocorticotropic hormone, progesterone, testosterone in the blood and melatonin in the urine of pregnant women. Results: the level of 6-sulphatoxymelatonin in the morning urine, regardless of the sex of the fetus, was higher in the seasons of the year with the predominance of the dark time of the day. Absolute levels of 6-sulphatoxymelatonin in urine in all women in 37-40 weeks of gestation were the lowest in the light-saturated summer and spring months of the year, while in the winter period its parameters were maximal. Melatonin production was statistically significantly higher in pregnant women with female fetuses during the fall and winter periods of the year. Regardless of the time of the year, in pregnant women with female fetuses, the absolute levels of estradiol and progesterone were higher than in the case of the male fetus. The highest values in the case of the female fetus were noted in the spring. Testosterone production was significantly higher in pregnant women with male fetuses mainly in the spring season. Stress resistance of pregnant women was higher in the summer months. Depending on the “sex of the fetus” factor, stress hormones in the summer had the highest values in pregnant women with male fetuses. Conclusions: the sex of the fetus is a significant factor affecting the seasonal variability of melatonin production, sexual and stress hormones in pregnant women due to the formation of the specificity of the systemic signaling between the maternal and the fetal organism in the dynamics of pregnancy

Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022

BACKGROUND. The clinical and epidemiological characteristics of diabetes mellitus (DM) and the quality of its therapy are the key prognostic dominant that determines the organizational aspects of the diabetic service. The continuous dynamic   monitoring of DM has been carried out in the Russian Federation (RF) since 1996 through the activities of the Federal Register of Diabetes Mellitus (FDR).AIMS. The aim of our study was to analyze the epidemiological characteristics of DM in the RF (prevalence, morbidity, mortality), the prevalence diabetic of complications, the state of carbohydrate metabolism (level of HbA1c) and the dynamics of the structure of glucose-lowering therapy (GLT) according to the FDR.MATERIALS AND METHODS. The database of FRD (https://www.diaregistry.ru/), 85 regions of the RF. The data are presented as of 01.01.2023 and in dynamics for the period 2010–2022.RESULTS. The total number of DM patients in the RF as of 01.01.2023 was 4 962 762 (3.31% of the population), including: Type 1 (T1) — 5.58% (277.1 ths), T2 — 92.33% (4.58 million), other DM types —2.08% (103 ths). The dynamics of prevalence over the 13-year period (2010→2022) was 146.0→191.0/100 ths people with T1, and 2036.2→3158.8/100 ths people with T2; morbidity in T1 12.3→8.2/100 ths population, in T2 260.1→191.4/100 ths population; мortality: T1 2.1→2.4/100 ths population, T2 41.2→86.1/100 ths of the population. The main cause of death was cardiovascular: in T1 38.6% cases, in T2 — 50.9%. Life expectancy (average age of death of patients): T1 was 52.7 years, the dynamics in males 50.9 → 50.7 years, females 62.1→56.0 years; in T2 — 74.2 years, males 69.5→70.4 years, females 74.2→76.1 years. The dynamic of DM duration from onset to the death: in T1 15.4→19.9 years; in T2 11→11.4 10.2→11.8 years. The proportion of patients with laboratory-measured HbA1c <7% in the dynamics of 2010–2022: with DM1 24.4%→29%, with DM2 41.5%→42.2%, with HbA1c ≥9.0%: with DM1 29, 4% → 20.4%, with DM2 13.8 → 9.0%.The incidence of diabetic complications as of 01.01.2023 in T1 and T2 patients: neuropathy 41.3% and 23.7%, nephropathy (CKD) 22.8% and 19.1%, retinopathy 28.9% and 12.3%, respectively. The structure GLT in T2 patients as of 01.01.2023: monotherapy — 41.6%; combination of 2 GLM — 30.0%, 3 GLM — 5.8%, insulin therapy in 18.3%.CONCLUSIONS. The information-analytical system FDR is a key tool for systematizing the most important epidemiological and clinical characteristics of DM based on data from real clinical practice, which allows optimizing the algorithm of patient management and improving the quality of care for diabetes

Daily periodicity of labor in pregnant women in physiological and complicated pregnancy depending on the sex of the fetus

Objective: the study aimed to reveal the daily periodicity of labor, the nature of melatonin metabolism, and the outcome of childbirth in women with a physiological and complicated pregnancy, depending on the sex of the fetus.Materials and methods: to study the chronophysiological characteristics of birth outcomes depending on fetal sex, 1 980 birth histories and stories of newborns were analyzed. The neonates were born between January 1 and December 31, 2016, in a maternity ward of the Federal State Budgetary Educational Institution of Higher Education “RostGMU” of the Ministry of Health of Russia. Melatonin production was identified by the level of urinary excretion of 6-sulfatoxymelatonin (6-SM) (its main metabolite) examining the morning portion of the urine of women by the ELISA method (at 8 am 3 ml of urine were collected in Eppendorf tube).Results: it was revealed that fetal sex modulated the activity of the central regulatory mechanisms responsible for the daily period functional processes in the female body and the initiation of labor. The largest number of spontaneous births by male fetuses occurred in the early evening before midnight when daily illumination was decreased, while the birth of girls was observed more often in the period from midnight to early morning. At the same time, mothers of boys had lower production of melatonin compared to that of girls’ mothers.Conclusions. The peculiarities of labor and birth complications associated with the sex of the fetus were identified

Dynamic monitoring of HbA1c in Russian regions: data comparison of mobile medical center (Diamodul) and national diabetes register of Russian Federation

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 <7% for T1DM is 13.3% and 11.7%; T2DM – 25.1% and 28.6%, in Kr and Vr, respectively; in NDR: T1DM – 37.4%, T2DM – 52.2%. The average HbA1c values in the Diamodul are higher than in NDR by 0.95% for T1DM, 1.41% for T2DM patients. The proportion of patients with HbA1c≥9% decrease in dynamic of examinations through years in T1: in Vr from 53.1% in 2005 and 55.8% in 2010 to 42.9% in 2019, in Kr from 53.2% in 2006 to 43.8% in 2019; also there were decreases in the average HbA1c values in Vr from 9.3% in 2005 and 9.4% in 2010 to 8.8% in 2019; in Kr from 9.1% in 2006 to 8.7% in 2019. In T2DM patients with the best parameters of DM control in a whole, the positive trends were less pronounced and are assessed as non-deterioration: the proportion of HbA1c≥9 % in Vr: 34.7%–34.7%–36.4%, in Kr 40.1%–28.4%; average values of HbA1c: 8.2%–8.4%–8.5% and 8.6%–8.4%, respectively. CONCLUSIONS: The data of the research clearly indicates the need for 100% inclusion of HbA1c in the examination standards in all DM patients at the primary level at least 1 time per year, in order to monitor the real clinical situation, the effectiveness of glucose-lowering therapy and its timely intensification to prevent development of complications

Trends in the epidemiology of chronic kidney disease in Russian Federation according to the Federal Diabetes Register (2013–2016)

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 201316. 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%, 0.623.5%, respectively. The CKD prevalence in dynamics 20132016 was 2171.42303.0 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) - 12.046.8% in T1; 10.050.4% in T2. The proportion of patients with a very high risk (stages C4/5 C3aA3 and C3bA2-3) progressively decreases: 13.46.7% in T1, 11.34.4% in T2. We observed relation between the CKD prevalence and DM duration. CKD develops in 5.1% patients if T15 years and in 48.0% if T130years; in T2 3.5% and 20.3%, respectively. The average age of CKD onset in T1 increased for 4,3yr (36,140,2), in T2 for 2,4yr (64,466,8), DM duration until CKD development increased in T1 11.814.2yr, in T2 7.68.2yr. 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