BACKGROUND: Data of real clinical practice in diabetes mellitus (DM) register allow to evaluate features and trends in structure of glucose-lowering therapy (GLT).

AIM: Тo analyze of structure of GLT received by patients with type 2 diabetes mellitus (T2DM) in Moscow region for 2018 and to evaluate its dynamics over 15 years.

METHODS: Analysis of GLT structure was carried out on basis of data from register of patients with DM in Moscow region, which is part of National register of diabetes mellitus in Russian Federation. In March 2018 it contained data on 211,792 T2DM patients of Moscow region. Structure of GLT administration was evaluated according T2DM duration, patient’s age and presence of cardiovascular diseases (CVD). Dynamics of GLT is analyzed from 2004 to 2018 yrs.

RESULTS: In 2018 non-insulin glucose-lowering drugs (NIGD) prescription prevailed (78.3%), insulin therapy was prescribed in 18.5% of patients, 3.2% of patients did not receive drug therapy. Most commonly prescribed NIGD were metformin (69.3%) and sulfonylurea (51.3%). Older patients more often than younger did not use GLT at all and less frequently received insulin therapy and iDPP-4. Insulin therapy was prescribed twice as often in patients with CVD compared with patients without CVD (29.6% and 15.5%). NIGD monotherapy has been less commonly used in patients with CVD (67.3% and 81.2%). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) were prescribed to patients with CVD GLP-1 RA – in 0.1% of cases, without CVD in 0.3% of cases, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in 1.1% and 0.6%. correspondently.

CONCLUSION: Metformin was most commonly prescribed drug in GLT structure for T2DM patients in the Moscow region in 2018 yr. Percentage of new drugs in the structure of GLT increased mainly due to iDPP-4, and secondly due to SGLT2 inhibitors. New classes of GLT were more often prescribed to patients of younger age, with diabetes duration up to 10 years, overweight or obese. Administration of NIGD with proven cardiovascular protection in presence of CVD is almost two times less than for those without CVD.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of β-cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion.

AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes.

MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.4±14.3 kg/m²)and 92 conditionally healthy donors (BMI=22.6±2.7 kg/m²) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software.

RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml.

CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content.

BACKGROUND: Tick-borne encephalitis (TBE) is an acute viral disease with activation of oxidative stress and increasing in cytogenetic instability. Clinical symptoms of infectious diseases usually more severe in patients with type 2 diabetes mellitus (DM2), especially in the case of burden in the genotype of mutant variants of glutathione-S-transferase genes GSTM1 and GSTT1.

AIMS: The aim of this study was to study the dynamics of the frequency of micronucleated cells in patients with acute TBE with concomitant DM2, depending on the burden of active and inactive variants of glutathione-S-transferase genes (GSTM1 and GSTT1) in the patient’s genotype.

MATERIALS AND METHODS: Totally, samples to make micronucleus assay were obtained from 138 patients with febrile illness of acute TBE, 64 of whom were diagnosed with concomitant DM2 (groups 3 and 4). As control groups, 57 healthy individuals (control 1) and 61 patients with DM2 (control 2) were examined. The samples of buccal cells for the micronucleus assay were repeatedly obtained from the individuals on the first day of admission, and also after 1 week, 1, 3 and 6 months. Polymerase chain reaction was used to analyze the variants of the GSTM1 and GSTT1 genes.

RESULTS: On the first days of the disease, significant increases in the frequency of micronucleated buccal cells were determined in all TBE patients as compared to controls 1 and 2 (P<0.001). Significant increases in the frequency of micronucleated buccal cells was revealed in groups 3 and 4 of the TBE patients who were carriers of inactive variants of the GSTM1(0) and GSTT1(0) genes, as compared to the subgroup of TBE patients with active variants of these genes (P<0.001). In all subgroups of TBE patients with concomitant DM2, the frequencies of micronucleated cells were significantly higher than in the subgroups of TBE patients without DM2 (P<0.001). Study of the dynamics of the frequency of micronucleated buccal cells, as compared to the control, demonstrated that the highest and long-lasting (within 6 months) cytogenetical effects were maintained in the group of TBE patients with genotype GSTM1(0)/GSTT1 (0) and concomitant DM2.

CONCLUSION: The most prolonged and highest increases in the frequencies of cytogenetically instable cells were determined in the group of acute TBE patients with concomitant DM2 who were carriers of the genotype with inactive variants of both GSTM1(0) and GSTT1(0) glutathione-S-transferase genes.

BACKGROUND: The development of diabetes mellitus (DM) is accompanied by hyperglycemia, which leads to the development of neuropathy. We assume that the individual characteristics of the organization of the autonomic nervous system (ANS) in humans affect not only the ability to withstand stress, but can determine the course of diseases, including diabetes.

AIMS: The study of the dynamics of heart rate variability and temperature sensitivity in rats against the background of hyperglycemia depending on the organization of the initial regulation of the heart under ANS.

MATERIALS AND METHODS: 70 male rats were randomized by weight and level of total heart rate variability (HRV) on animals with initially low and high levels of total HRV. Diabetes was modeled by a single i.p. injection of streptozotocin (STZ). The control group received a single i.p. injection of citrate buffer (CB). Before the induction of diabetes, as well as on 21, 42 and 70 days after the injection of STZ, a comprehensive examination of rats’ condition was carried out: 1) assessment of HRV; 2) analysis of temperature-pain sensitivity; 3) assessment of glucose and ketone bodies in the blood. Similarly, animals in the CB group were examined.

RESULTS: The change in HRV and temperature-pain sensitivity in rats depends on the initial level of HRV. In rats with low variability, the reaction time in the pain test increased by 8–32% from the 28th day of the experiment, from 21 days the bradycardia increased and the decrease in individual HRV indices at rest, but not the response of these parameters to cold stress.

CONCLUSION: The development of ANS’s lesion depends on the initial level of HRV. Low variability animals are more resistant to hyperglycemia: the normal ranges of CP reactions from the side of HR, the parameters of total HRV and the CVHS contribution to it are longer, but there is a loss of temperature sensitivity. Initially, highly variable rats with the development of diabetes do not lose temperature sensitivity, but demonstrate an imbalance in the regulatory circuits of heart rate and HRV.

This article represents a review of trials on the relationship between the use of modern technologies in the treatment of diabetes, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and the psychological characteristics of patients. The review includes Russian studies and foreign publications.

The analysis showed that the psychological aspects of using CSII are considered more often than CGM. Most Russian authors agree that the use of technology is associated with an increased psychological well-being of patients. Foreign researchers generally agree with the same point of view but also report a weaker correlation.

One of the most significant conclusions of this analysis is that the use of modern technologies itself does not guarantee an improved quality of life (QOL) and psychological well-being, but technologies such as CSII and CGM provide patients with opportunities to achieve greater effectiveness in treating diabetes, improving clinical and metabolic parameters and therefore improving QOL. However, the use of these devices, as well as many other technological tools, is associated with certain psychological problems, both in terms of their acquisition and influence on patients’ subjective well-being. Early diagnosis and prevention of such problems should be one of the tasks in preparing patients for the use of modern technologies. A positive effect on both clinical and metabolic indicators as well as on the mental sphere and social life of patients can be achieved only by combining complete training (optimally—according to specialised programmes) with medical support.

Obesity is a worldwide problem of the last century, the prevalence of which has reached pandemic proportions in developed countries. Over the past few years, a considerable amount of data has been gathered, reporting a direct link between changes in gut microbiota and the development of obesity, as well as related diseases, primarily, diabetes mellitus type 2. The elaboration of optimal methods of prevention and treatment regimens of these diseases needs to structure the existing knowledge about the mechanisms of development of metabolic disorders, the role of intestinal microbiota in the latter and possible therapeutic “targets”. This review examines the role of microorganisms in the human body, with the main focus on the developmental origins of metabolic disorders using animal models and accumulated experience of research on their effects on the human body, and also discusses possible treatment options, including bariatric surgery, fecal microbiota transplantation, the use of pre- and probiotics and certain particular groups of glucose-lowering drugs.

BACKGROUND: In coexistence of diabetes mellitus type 1 (DM1) with severe autoimmune and inflammatory diseases some patients need simultaneous administration of insulin and glucocorticoids (GC). GC therapy in patients with DM1 can worsen glycemic control.

AIM: To determine characteristics of insulin therapy of DM1 in children and adolescents receiving GC.

DESCRIPTION OF CLINICAL CASES: We observed 5 patients with DM1 receiving GC for juvenile idiopathic arthritis (JIA), juvenile systemic sclerosis (JSS), juvenile dermatomyositis (JDM), ulcerative colitis (UC), and reactive arthritis (RA).

Intra-articular administration of GC did not significantly influence glycemic control.

In case of GC pulse therapy hyperglycemia and increased insulin requirements were recognized in 3–6 hours after GC receipt, persisted from few hours up to 3 days after each administration.

While therapy with oral GC in high doses the worst glycemic control was registered in daylight hours. To overcome insulin resistance change of time of injection and 10%-increase of long-acting insulin analogue, additional injections of ultrashort-acting insulin analogues, temporal prescription of short-acting human insulin were used.

While GC therapy insulin daily dose was individual and could reach 2.0 U/kg. After transition to maintaining doses of GC or discontinuation of GC therapy patients returned to standard or relatively low insulin requirements.

Levels of glycosylated hemoglobin differed significantly among patients at different stages of treatment, were maximal while long-term therapy with high doses of oral GC, but mostly depended on patient’s compliance.

CONCLUSION: Bettering of glycemic control while receiving GC can be reached by timely dose correction of insulin therapy, selection of individual schemes, taking into account time of receipt and pharmacokinetic characteristics of GC. Adherence of the patient and his family to treatment of DM1 plays an important role in glycemic control.

MODY1 and MODY3 represent rare causes of diabetes in pregnancy. Establishing a molecular diagnosis of MODY1 or MODY3 during pregnancy may be important for minimizing risk of perinatal complications and for improving glycemic control after pregnancy. The objective of the study was to evaluate the contribution of mutations in HNF4A and HNF1A genes in development of diabetes in pregnancy and to describe clinical characteristics of diabetes in pregnancy associated with these mutations. 230 pregnant women (20-43 years) with different type of glucose intolerance complicated during their current pregnancy were included in the study. A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. Heterozygous mutations in HNF4A and HNF1A genes were detected in 3% of cases. Mutations p.I271T in HNF4A gene and p.L148F, p.Y265C, p.G288W in HNF1A gene were novel. This study includes a description of patients with pregnancy diabetes due to mutations in hepatocyte nuclear factors.

The Scientific Advisory Board, chaired by Professor G. R. Galstyan (cochair - A.V. Zilov), met in Moscow on 19 June 2018 to discuss the possibilities of improving the results of diabetes mellitus (DM) treatment by considering glycaemic variability (GV) as an additional criterion for effective glycaemic control (especially in patients receiving insulin therapy) and as one of the goals of treatment in patients with unstable glycaemia.

The purpose of the working meeting was to develop a strategy for the introduction of GV as a predictor and as an additional criterion for assessing the effectiveness and safety of hypoglycaemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality.

The aims of the working meeting were to conduct a comprehensive data analysis of the relationship between GV and hypoglycaemia; to gather and analyse published data and the experience of decrease in GV and improved outcomes of diabetes against the background of different types of insulin therapy; to compare existing methods of glycaemia monitoring and GV assessment and examine their validity and availability in real practice in the context of limited budget and to analyse the informativeness and clinical and prognostic significance of various parameters of GV assessment and to determine their reasonable ‘minimum’ for a comprehensive assessment of GV as a criterion for evaluating the effectiveness of DM treatment and the predictors of negative diabetes outcomes.

The following reports were presented during the discussion: ‘Glycemic variability: clinical and prognostic value. Types of glycemic variability’ (Candidate of Medical Sciences, assistant Professor Zilov A.V.); ‘Methods of assessment of variability of glycemia in clinical trials and routine practice’ (PhD, Professor Markova T. N.); ‘Current international and national recommendations on glycemic monitoring’ (PhD, Professor Galstyan G. R.) and ‘Peculiarities of glycemic variability and its evaluation among children and adolescents’ (Candidate of Medical Sciences Vitebskaya A.V.).