BACKGROUND: Glucose variability (GV) is recognized as a risk factor for microvascular and macrovascular complications of diabetes and hypoglycemia. A number of indices have been proposed to assess GV, but there are no generally accepted normal reference values for these indices.

AIM: To establish the reference values of 24-hour, day-time and nocturnal GV parameters derived from continuous glucose monitoring (CGM) data in young and middle-aged subjects with normal glucose tolerance.

MATERIALS AND METHODS: A blind 6–7-day CGM was performed in 50 subjects, 20 men and 30 women, aged from 22 to 56 years, with normal values of the oral glucose tolerance test and glycated hemoglobin A1c. GV parameters: Standard Deviation (SD), Coefficient of Variation (CV), Mean Amplitude of Glycemic Excursions (MAGE), 2-hour Сontinuous Overlapping Net Glycemic Action (CONGA), Lability Index (LI), J-index, Mean Absolute Glucose rate of change (MAG), М-value, High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI) were calculated for 24-hour records, day-time (6.00–23.59) and night (0.00–5.59) hours.

RESULTS: 95% confidence intervals for 24-hour records were: mean glucose 5.2–6.6 mmol/L, SD 0.5–1.3 mmol/L, CV 9.1–23.2%, MAGE 1.2–3.2 mmol/L, CONGA 4.3–5.9 mmol/L, MAG 0.5–2.1 mmol×L-1×h-1, LI 0.1–1.3 (mmol/L)2×h-1, J-index 11.3–18.6 (mmol/L)2, M-value 0.4–4.4, HBGI 0.1–1.9, LBGI 0.3–3.2.The following day-time values were estimated: mean glucose 5.3–6.7 mmol/L, SD 0.5–1.4 mmol/L, CV 8.7–24.5%, MAGE 1.2–3.4 mmol/L, CONGA 4.3–5.9 mmol/L, MAG 0.6–2.5 mmol×L-1×h-1, LI 0.2–1.6 (mmol/L)2×h-1, J-index 11.2–19.6 (mmol/L)2, M-value 0.2–3.8, HBGI 0.1–1.9, LBGI 0.3–3.0. The values for nocturnal hours were: mean glucose 4.7–6.4 mmol/L, SD 0.3–0.9 mmol/L, CV 5.3–17.9%, MAGE 0.7–2.7 mmol/L, CONGA 4.1–5.8 mmol/L, MAG 0.3–1.8 mmol×L-1×h-1, LI 0.05–0.8 (mmol/L)2×h-1, J-index 8.5–17.5 (mmol/L)2, M-value 0.2–5.2, HBGI 0–0.9, LBGI 0.3–3.6.

CONCLUSION: The obtained reference values of the GV indices should be taken into account in research and in clinical practice when interpreting the results of CGM in young and middle-aged people.

Background: The effectiveness and safety of a fixed combination of insulin glargine 100 ME/ml and lixisenatide for treatment of patients with type 2 diabetes (T2DM) has been demonstrated in randomized clinical trials, but there are still not enough data of it`s usage of it real clinical practice.

Aim: To describe the baseline characteristics of patients with T2DM who started treatment with a fixed ratio combination of insulin glargine 100 ME/ml and lixisenatide in the period from November 2018 to July 2020, and to evaluate the effectiveness of using fixed combination of insulin glargine 100 ME/ml and lixisenatide in for 6–12 months of therapy in a real outpatient practice.

Materials and methods: SOLO was a retrospective cohort multicentre study conducted in Russia, Moscow. Adults (≥18 years) with T2DM and HbA1c≥7% in case of availability of medical records during ≥180 days before and ≥1 HbA1c level during 150–210 days after start of treatment with Soliqua SoloStar® were eligible.

Results: A total of 383 people with T2DM were included. Baseline characteristics were the following (mean±SD): age 59.9±8.3 years; BMI 36.4±6.3 kg/m2; proportion of patients with BMI≥35 kg/m2 — 52.2%; HbA1c 9.14±1.08%. 65% of patients received oral antidiabetic drugs (OAD) before start of treatment with fixed combination of insulin glargine 100 ME/ml and lixisenatide ; 31.3% of patients were switched from combination of OAD with basal insulin, 1.04% of patients received other therapy (GLP-1 RA, basal-bolus insulin treatment, basal insulin monotherapy), and 2.61% of patients did not receive any hypoglycemic therapy. HbA1c level was 7.78±0.8% after 6 months of treatment and 7.4±0.61% after 12 months. There was a significant decrease of body weight from the baseline value 101.62±20.64 kg by 1.96±4.03 kg at month 6 and by 3.13±4.71 kg at month 12 (p<0.001) Overall, 4 patients (1.04%) reported symptomatic hypoglycemia (glycemia ≤3.9 mmol/L); no episodes of severe hypoglycemia were registered.

Conclusion: In a real-life setting in Russia, initiation of a fixed combination of insulin glargine 100 ME/ ml and lixisenatide in people with T2DM uncontrolled on OADs or combination of OADs with basal insulin resulted resulted in an improved glycemic control and body weight change with low risk of hypoglycemia compared to baseline

BACKGROUND: Diabetic nephropathy is a specific kidney damage that affects up to 40% of type 1 diabetes mellitus patients. There is still insufficient knowledge about oxidative stress at the different levels of albuminuria.

AIM: To assess the indicators of oxidative damage to lipids, DNA and antioxidant defense in men with type 1 diabetes mellitus and albuminuria different levels.

MATERIALS AND METHODS: The study was conducted during 2018–2019. The main group included 56 men of reproductive age with type 1 diabetes mellitus (T1DM) divided into 2 groups: 24 patients with albuminuria level A1 (group A1) and 32 patients with albuminuria level A2 (group A2). The control group consisted of 28 healthy men. The oxidative stress indicators content, as well as the activity of antioxidant defense system various links was evaluated. Spectrophotometric, fluorimetric and enzyme immunoassay methods were used.

RESULTS: In patients of the A1 group there were higher values of the median of primary — conjugated dienes, secondary — ketodienes and conjugated trienes, final — Schiff bases products and 8-hydroxy-2’-deoxyguanosine in comparison with the control. Similar changes in patients of the A2 group were found. Intergroup differences related to increased median values of TBARs and 8-hydroxy-2’-deoxyguanosine in patients of the A2 group compared with A1 group. The activity of the antioxidant defense system in A1 group relative to the control by increased values of the glutathione peroxidase, reduced glutathione, oxidized glutathione median, and retinol was characterized. A2 group had higher values of glutathione peroxidase, reduced glutathione and oxidized glutathione medians in comparison with controls. Correlation analysis in A1 group showed the relationships between the duration of the disease and the products of lipid peroxidation, glycated hemoglobin with 8-hydroxy-2’-deoxyguanosine. In A2 group, there was a relationship between the albumin/creatinine ratio and the duration of the disease, glomerular filtration rate and creatinine level.

CONCLUSION: In men with T1DM, regardless of the albuminuria level, there are higher values of the oxidative damage lipids and DNA parameters, as well as the presence of close relationships between these parameters and the duration of the disease, which can be used to develop potential strategies for the prevention and early therapy of diabetic nephropathy.

BACKGROUND: Diabetes mellitus (DM) and hypertension are risk factors for cerebral stroke, which are exacerbated by the combination of these diseases. Identifying the factors involved in the development of subclinical brain damage could change the therapeutic strategy for protecting the brain.

AIM: to study severity of MRI- sings of brain damage and to identify factors associated with their development in patients with type 2 diabetes and RHTN.

MATERIALS AND METHODS: 46 patients with type 2 DM and RHTN were included in a single-center observational uncontrolled study. Patients underwent brain MRI (1.5 Tesla) with calculation of Evans’s index (EI), clinical and lab examinations (HbA1c, glucose, insulin, C-peptide, leptin, resistin, TNF- α, hsCRP, blood aldosterone, insulin-like growth factor-1 (IGF-1)), measurement of the office and ambulatory blood pressure (BP), assessment of peripheral and cerebral vasoreactivity (test with hyperventilation and breath holding).

RESULTS: The most frequent MR brain changes were white matter lesions (WML) in periventricular region (PVR) (89%), focal WML (52%) and expansion both of the ventricles (45%) and subarachnoid spaces (65%). Multiple direct correlations were revealed between parameters of carbohydrate metabolism with the degree of WML in PVR and the density of the MR-signal in the basal nucleus (BN), as well as with EI. Adipokines had a direct relationship with the size of the chiasmatic cistern and IE (for resistin), as well as with the density of the MR signal from the BN and IE (for leptin), that was also directly related to the IGF-1 level. The aldosterone level positively correlated with the size of III ventricle. An increase in TNF-α and hsCRP was accompanied by an increase in the density of the MR-signal in the PVR. Impairment of cerebrovascular reactivity is associated with an increase in the density of the MR-signal in PVR and with indirect signs of cerebral atrophy (increase in EI, the size of cisterns and lateral ventricles). Impairment of peripheral vasoreactivity had direct relationship with EI and the expansion of the III ventricle. There were no direct correlations between the severity of MR-sings of brain damage and BP levels.

CONCLUSION: The combination of type 2 DM with RHTN is characterized by a high frequency of WML and liquorodynamics disturbances, which related with metabolic, neurohormonal and hemodynamic factors in the absence of a direct relationship with the degree of BP increase

Background: Type 2 diabetes mellitus (T2DM) increases the risk of developing cardiovascular disease. The search for factors interrelated with the development of major adverse cardiovascular events (MACE) in patients with T2DM over a long period of observation is urgent.

Aim: To reveal the relationship of clinical, laboratory and echocardiographic parameters with the development of long-term MACE in T2DM.

Materials and methods: 94 patients with T2DM (mean age — 55,3 ± 5,5 years, 65% of women) without manifestations of moderate and severe chronic heart failure (CHF), impaired renal function, severe somatic pathology underwent a ­complete clinical and laboratory examination. Echocardiography and 6-minute walk test (6mwt) were performed. The plasma level of the N-terminal propeptide of natriuretic hormone B-type (NT-proBNP) was determined. The variability of fasting blood glucose and intraday glycemic variability were measured by calculating the standard deviation (SD) and the coefficient of variation (CV) of at least 3 blood glucose values for 3 days. Analysis of MACE (death from any cause, myocardial infarction, stroke, decompensation of CHF, myocardial revascularization for emergency indications) was performed after 8,8 ± 0,72 years (n=88). Patients with T2DM were divided into 2 groups — without MACE (group 1, n=54) and with MACE (group 2, n=34). The search for predictors of long-term MACE in T2DM was carried out using the method of logistic regression.

Results: Initially, group 2 differed from group 1 in a longer duration of T2DM, a higher incidence of stable coronary heart disease (55,9% vs 27,8%, p = 0,008), a higher presence of albuminuria>30 mg/day (66,7% vs 37,3% , p=0,008), a higher presence of initial symptoms of CHF (67,8% vs 21,8%, p=0,001), greater fasting glucose variability (SD 2,07 mmol/l vs 1,2 mmol/l, p=0,003), greater intraday glucose variability (SD 2,3 mmol/l vs 1,6 mmol/l, p=0,001, CV 28,2% vs 18,8%, p=0,001), higher levels of NT-proBNP (46,9 pg/ml vs 24,2 pg/ml, p=0,012), larger left atrial size (4,4 cm vs 4,1 cm, p=0,039), shorter 6mwt distance. The logistic regression method revealed the parameters that are most interconnected with long-term MACE in T2DM: intraday glycemic CV (p=0,0012), left atrial size (p=0,02) and initial manifestations of CHF (p=0,03).

Conclusion: The development of long-term MACE in T2DM is associated with an increase in glycemic variability, an increase in NT-proBNP level, an increase in the left atrial size, and a decrease in exercise tolerance. According to logistic regression data, the most significant indicators associated with adverse outcomes are an increase in intraday glycemic CV, an increase in the left atrial size, and the presence of initial symptoms of CHF.

BACKGROUND: Monogenic diabetes mellitus (MDM) is a rare form of diabetes mellitus (DM) which caused by one or more mutations in one of the genes that cause pancreatic β-cell dysfunction. Despite the sufficient knowledge of the most common subtypes of MODY, cases of MDM are undiagnosed and classified as type 1 diabetes mellitus and type 2 diabetes mellitus.

AIM: To study the clinical, laboratory characteristics, as well as age-related features of GCK-MODY in children.

MATERIALS AND METHODS: The studied population is patients with GCK-MODY under the age of 18 years. The diagnosis was confirmed by genetic test, a heterozygous mutation was identificated in the GCK gene.

RESULTS: MODY-GCK was verified in 144 patients (131 probands and 13 siblings) under the age of 18 years. Missense mutations were detected in 80.2% (n=105). Mutation was detected in one case in 59.6%. The most common missense mutations were p.G261R (n=7) and p.G258C (n=6). The age of diagnosis of carbohydrate metabolism disorders was 7.6 years [4.0; 11.2]. In 72.2% carbohydrate metabolism disorders were diagnosed accidentally, in 16.7% the examination was provided due to a family history of diabetes, 11.1% had clinical symptoms of diabetes. Fasting glycemia at diagnosis was 6.8 mmol / l [6.4; 7.3], HbA1c — 6.4% [6.1; 6.7]. At examination, the level of fasting glycemia corresponded to normal values in 16.4% of patients, impaired fasting glycemia — in 57.8%, diabetic — in 25.8%. In 62.3% of patients was impaired glucose tolerance, in 18.9% — to diabetic values, and in 11.7% of patients — to a normal level at 120 minutes during the oral glucose tolerance test. A moderate positive correlation was found between the age of examination and the levels of fasting glycemia (r=0.347, p<0.01), C-peptide (r=0.656, p<0.001), and insulin (r=0.531, p<0.001). Insulin resistance (IR) (HOMA index) was detected in 21 patients (14.5%), obesity — in 6 patients (4.2%). In 9 patients (6.25%) was revealed a moderate increase in the titer of specific pancreatic antibodies (AT). The presence of IR, obesity, AT did not affect the level of HbA1c. In 92.3% diet was priscribed, in 4.2% insulin was prescribed, 2.1% — metformin, 1.4% — sulfonylureas.

CONCLUSION: In children, disorders of carbohydrate metabolism in GCK-MODY are diagnosed accidentally, asymptomatically at any age from birth, and are characterized by a combination of impaired fasting glycemia and impaired glucose tolerance and, as a rule, do not require antihyperglycemic therapy

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by the development of absolute insulin deficiency. In some patients residual insulin secretion may persist for a long time. C-peptide is a widely used to measure the pancreatic beta cells function, in clinical practice and in research studies.

AIM: To assess C-peptide levels and presence of islets autoantibodies (Ab) in children with different duration of T1DM and to identify factors associated with the preserved secretion.

MATERIALS AND METHODS: Single-center cross-sectional study including data from 703 cases of children with T1DM, examined in the Endocrinology Research Center in 2016-2020, who was underwent a study of C-peptide levels and was positive for one or more islets antibodies (ZnT8, IA-2, GAD, ICA, IAA). There were 3 groups of patients: 1st — T1DM duration < 1 year, 2nd — from 1 to 5 years, 3rd — > 5 years.

RESULTS: The median of the fasting C-peptide level in the 1st group was 0.6 ng/ml [0.27; 1.09]; in the 2nd group — 0.2 ng/ml [0.01; 0.8]; in the 3rd group — 0.01 ng/ml [0.01; 0.037]. The preserved secretion of C-peptide (> 0.6 ng/ml) was determined in 51.4% in the 1st group, in 31.4% — in the 2nd group and in 11.4% in the 3rd group. In patients with obesity during the first year from the T1DM diagnosis C-peptide levels above 1.1 ng/ml was determined significantly more often (65.2%), as well as at the period of 1 to 5 years of the disease (35.7%), compared with children with normal BMI (18.5% and 14.5%, respectively) or overweight (15.7% and 19%, respectively), p <0.01. A negative correlation was found between C-peptide levels and the duration of T1DM (r = -0.489, p = 0.000), the daily dose of insulin (r = -0.637, p = 0.000), a positive association was found with the age of diagnosis of T1DM (r = 0.547, p = 0.000). The frequency of the presence of one type of islets autoantibodies in all groups was 29.5%, 2 types — 33.6%, 3 and more types — 36.9%. The titer of IA-2, ZnT8 decreased with the disease duration (p <0.05 and p <0.01, respectively), while the titer of ICA increased (p <0.01). No associations between the types, number, antibodies titer and C-peptide levels, age of disease manifestation were found.

CONCLUSION: C-peptide levels in children with T1DM in groups with older age at diagnosis and with obesity is significantly higher for the first 5 years of the disease. The study have shown the titer of IA-2, ZnT8 is decreasing with the disease duration, in turn, the frequency of detection of ICA increases. No association between C-peptide levels and the type, number and titer of antibodies were found.

Background: Sulfonylureas (SU) are often used for second and third line type 2 diabetes mellitus (T2DM) therapy. Currently, there are no unified recommendations governing the choice of drugs for the second line therapy. This requires clarification.

Aim: To examine Moscow Region DM register data for assessing ongoing antihyperglycemic therapy and its correspondence to current local and international T2DM treatment recommendations, as well as actual clinical recommendations for the treatment of T2DM patients and COVID-19.

Materials and methods: The structure of glucose-lowering therapy with non-insulin drugs (NID) was studied in T2DM patients according to the data T2DM register of Moscow region. The analysis was carried out on 06.02.2021. We analyzed the general group of T2DM patients (237479 people), group 60 years and older (188644 patients), T2DM patients who have had COVID-19. Newly diagnosed T2DM individuals were analyzed for 2020 (5088 people).

Results: Glucose-lowering therapy is received by 97.6% of T2DM patients. Of these, 79.07% take NID, insulin + NID - 11.37%. Monotherapy is received by 44.4% of patients, a combination of two drugs - 29.3%, out of three - 5.3% of patients. Metformin is the leader in prescribing NID (69.4% of all T2DM patients and 81.3% in newly diagnosed patients). SU are in second place in T2DM treatment (50% of all patients, 24.1% in newly diagnosed patients), iIDPP-4 is in third place (12.1% and 12.6%, respectively). Among patients of 60 and more years old, 25.99% of patients take gliclazide MR, 14.3% glibenclamide, 7.7% glimepiride. Mortality from COVID-19 depends on the diabetes duration.

Conclusion: According to the DM register, half of the T2DM patients and a quarter of T2DM newly diagnosed patients get SU. As a first-line drug, SU is on the second place after metformin and are most often used in double and triple combinations of T2DM therapy. In the older age group on SU, preference is given to gliclazide MR.

BACKGROUND: For the past few decades, there have not been many studies done regarding diabetic patients’ perspectives. Diabetes mellitus is serious long-term care required for older patients. The facilitators have an important role in supporting diabetes patients.

AIM: The study aimed to assess and compare patients’ and caregivers’ perception of diabetes self-monitoring (DSM) and affects the Diabetes Self-Management Instrument (DSMI) of type-2 diabetic patients in both glycemic controlled and uncontrolled patients.

MATERIALS AND METHODS: The descriptive cross-sectional qualitative method was used to gather data from 25 participants among type II diabetes patients. Patients were recruited from the outpatient diabetes clinics in southern Thailand. Data were collected using a semi-structured in-depth interview guide and the focus group discussion. A thematic analysis approach was used to process the data.

RESULTS: From this study, 60% of the participants were among the uncontrolled glycemic group while 40% were the controlled group. The controlled group was found to have better self-management in the five themes of a healthy diet, regular exercise, medication taking, and risk prevention than the uncontrolled group. T2DM elderly in a controlled group has self-awareness and diabetic management intention higher than the uncontrolled group. The patient’s attitudes revealed five themes described fours themes of diabetic self-management intentions as reasoning, deciding, acting, and evaluating to perform self-management of older T2DM patients.

CONCLUSION: The elderly T2DM in the glycemic control group had self-awareness and intended to manage their diabetes and received more family support than those who were unable to control their blood sugar levels. Perceptions of elderly diabetic patients, their caregivers, and health workers revealed a common concern for behavioral intentions: obtaining self-care support from healthcare professionals and their families were the most important aspect of glycemic control in the elderly.

The prevalence of diabetes mellitus has increased in recent decades. The most common ophthalmic manifestations of diabetes mellitus are retinopathy, epitheliopathies, corneal erosion and dry eye syndrome, the symptoms of which are more pronounced than in people without diabetes. The meibomian glands, which are the producer of various lipids, participate in the formation of the lipid layer of the tear film, which prevents the evaporation of the water-mucin phase and ensures the preservation of homeostasis of the ocular surface. Meibum is a lipid-rich secret produced by fully differentiated meibocytes. Impaired insulin secretion, insulin resistance, absolute insulin deficiency, as well as hyperglycemia, potentiate the development of oxidative stress and a cascade of metabolic changes, leading to a change in the anatomical and functional state of the meibomian glands, which affects the qualitative and quantitative secretion. Cytological abnormalities, as well as the structure of the excretory ducts of the meibomian glands in patients with long-term diabetes mellitus, were established using the method of laser scanning microscopy. Using the method of mass spectrometry, it is possible to determine the patterns of changes in the chemical composition of meibum in patients with diabetes mellitus. The data obtained can become one of the criteria for predicting the course, reflect the degree of compensation and / or progression of diabetes mellitus.

At the present time, a simultaneous pancreas-kidney transplantation (SPKT) is an effective method of treatment for patients on renal replacement therapy by hemodialysis program in the outcome of the terminal stage of diabetic nephropathy. This method of treatment solves several problems: it reduces the severity of intoxication syndrome, contributes to the achievement of euglycemia in most cases, which certainly allows to slow the progression of micro- and macrovascular complications of diabetes. Despite of positive effect of euglycaemia and kidney function normalization, the accumulated metabolic memory legacy of long-term uncompensated diabetes mellitus is realized, which makes a posttransplantational rehabilitation of patients difficult. A duration of hemodialysis therapy is known as a cardiovascular events risk factor, which affects the surgery result and favorable posttransplant period. More often after successful SPKT microvascular diabetic complications are stabilized, but macrovascular diabetic complications, diabetic neuroosteoarthropathy and mineral and bone disease are progressed. That’s why is necessary to perform regular examination after SPKT by a team of specialists, including nephrologist, endocrinologist, cardiologist, ophthalmologist with correction of ongoing therapy. Therefore both the preparation of  the patient for transplantation with the earliest possible placement on the waiting list and the post-transplant rehabilitation afterwards are extremely important.

On April 18, 2022, Honored Doctor of the Russian Federation, Honorary Head of the Department of Pediatric Endocrinology of the Russian Medical Academy of Postgraduate Education, Doctor of Medical Sciences, Professor Elvira Petrovna Kasatkina, died at the age of 93.