Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research.

Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016.

Materials and methods: The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters.

Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUC_ins0-T, and 85.43% - 115.64% for the PD-parameter AUC_{GIR0_T}, which fall within the specified limits of 80% - 125% to establish comparability between drugs.

Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®.

Background: Treatment options in patients with an acute Charcot foot is not well standardized and still challenging.

Aims: To evaluate the results of the non-operative treatment of patients with active stage of diabetic charcot arthropathy in outpatient foot clinic and to identify factors influenced on treatment results.

Materials and methods: Medical files of 141 patients with unilateral ulcer-free active charcot arthropathy were reviewed. 78 patients agreed for treatment (total contact cast or walker), 63 patients refused of treatment (follow-up only). The time of resolution of the acute stage, severity of final deformities and foot-related complications were evaluated. Refusers were asked about the cause of their decision.

Results: Mean delay of the diagnosis was 3,2±2,8 months. Main causes of the refuse were: mistrust to doctor - 38%, problems with employment - 33%, home/family problems - 18%, medical reasons - 11%. Median healing times (months) in the treatment group vs controls: 9 (6 - 19) 15 (13 - 25) (p=0,001) and progression of the initial deformity: 14% and 35%, respectively (p=0,01). Foot-related complications: 17,5% in the treatment group and in 55,6% of controls (including 6 amputations) (p=0,001). Frequency of breaking the cast/walker - 32%/16,6%. Foot lesions due to cast/walker: 13,6%/41,7% (p<0,01). Median healing times (months) with walkers - 13 (11 - 19), with casts - 9 (6 - 15) months (р=0,02). The use of crutches shortened healing time.

Conclusions: The significant delay of diagnosis was revealed. The refuse rate in our cohort was high and main causes of the refuse were social and psychological. Neglect of treatment leads to high frequency and severity of foot-related complications. We noticed high rate of breaking of walkers and casts and device-related foot lesions. Total contact casts were more effective and safe compared with walkers.

Introduction: Ankle Brachial Index (ABI) is one of the common non-invasive diagnostic tools available for diagnosing Peripheral Arterial Disease (PAD). However, it has been observed that for an individual diagnosed with both PAD and Type 2 Diabetes Mellitus (T2DM), ABI tends to give false diagnostic value because of the calcification of the major lower limb arteries. Therefore, the health care professionals are at times misled for the diagnosis of PAD. To overcome this another diagnostic tool Toe Brachial Index (TBI) was suggested to perform. However, there is limited literature on performing both ABI and TBI in the given population in a single study.

Aim: The main focus of this study is to report the profile of ABI and TBI along with classical symptoms like claudication pain, palpation of pulse and history of T2DM for the screening and diagnosis of PAD in T2DM.

Materials And Methods: In this cross-sectional observational study, a total of 121 participants diagnosed with T2DM were recruited for the study as per the inclusion criteria. Detailed demographic details of the participants were noted. Diagnostic tool including both ABI and TBI were performed for all the participants and the data was analysed.

Results: Among 121 participants, only 3 participants had both ABI and TBI positive indicating positive diagnostic test for PAD and 106 participants had both ABI and TBI negative. However, in the remaining 12 participants, 10 showed TBI positive but ABI negative and 2 had ABI positive but TBI negative.

Conclusions: Based on our study we have reported the profile of PAD in T2DM individuals, which is found to be 10.75.%. Therefore, it can be concluded that ABI and TBI both should be performed to rule out any complication. This will be beneficial in early screening and detection of neuro ischemic changes in foot and subsequently to prevent amputation.

The review focuses on the new WHO classification published in 2019. Unlike the previous classification, this classification does not recognize subtypes of T1DM and T2DM and offers new types of diabetes: “hybrid types of diabetes” and “unclassified diabetes”. This classification provides practical guidance to clinicians for assigning a type of diabetes to individuals and choose appropriate treatment (whether or not to start treatment with insulin), particularly at the time of diagnosis. This review presents the variety of forms of diabetes, the features of their clinical picture, and also emphasizes the importance of molecular genetic and immunological studies to identify types of diabetes and determine personalized therapy. The selection of “hybrid forms” of diabetes is due to the fact that the treatment of these types of diabetes has its own characteristics associated with the specific pathogenesis of diseases. However, it is obvious that further studies should relate to the study of the mechanisms of damage and decrease in the function of в-cells. Perhaps future classification systems and, as a consequence, personalized treatment will focus on various mechanisms of damage to β-cells.

Diabetic nephropathy (DN) is specific kidney damage in patients with diabetes mellitus. DN develops relatively often in pregestational diabetes patients (5,9-26%) and stills one of the main limitations for successful pregnancy in this patients’ group. Advanced DN increases risks of poor pregnancy outcomes for women and fetuses including chronic kidney disease (CKD) progression, high rate of preeclampsia, preterm deliveries, Cesarean sections, perinatal mortality and neonatal morbidity. At the same time there are more and more successful pregnancies with advanced DN in the wold.

In our paper we systematize global experience of planning and management pregnancies with type 1 diabetes and DN in different stages of renal impairment. We discuss role of nephroprotective therapy in preconception care, achievement and maintaining blood pressure goals, multidisciplinary team care for improvement pregnancy outcomes in type 1 diabetic women with DN.

Hyperuricemia is an increase of uric acid (UA) concentration in blood serum >420 pmol/L in men or >360 pmol/L in women and is considered to be a common biochemical abnormality. This condition shows that the extracellular fluid is oversaturated with urates, which concentration exceeds the limit of their solubility. This fact predisposes to the formation of crystals of sodium salt of UA and results in gout, urolithiasis, and other diseases. The frequent combination and relationship between purine and carbohydrate metabolism were noted in previous studies. In this regard, the choice of drugs for correcting these disorders should consider the possibility of a combined positive effect on the UA and serum glucose levels. The hypoglycemic drugs with pleiotropic effects on several metabolic syndrome components are considered to be of particular interest. Currently, one of the most frequently prescribed groups of drugs in the treatment of diabetes mellitus type 2 are dipeptidyl peptidase-4 inhibitors, which affect the level of incretins (gliptins). These drugs can be potentially attractive in patients with purine metabolism disorders since the available data indicate that these drugs affect UA level.

With the growing prevalence of type 2 diabetes mellitus (T2DM) the possibility of treating it with available drugs is one of the main issues. Although glycemic control and reduction of micro- and macrovascular outcomes remain important aspects of treatment, the main limiting factors are the availability and cost of oral hypoglycemic agents. Although newer agents, such as sodium -glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists, potentially being valuable for patients with insulin resistance and cardiovascular complications, they are relatively expensive and have limited availability. Second-generation sulfonylureas effectively reduce glycated hemoglobin and contribute to the prevention of micro- and macrovascular complications of T2DM The review substantiates the role of Gliclazide MR as a more affordable drug for the treatment of T2DM, the safety of which has been confirmed by many studies; cardio-and nephroprotective effects are shown, as well as mechanisms for influencing в-cells of the pancreas and extrapancreatic effects through activation of phospholipase C and the G-protein-сoupled-receptors (GPCR) are analyzed. The latest data on the assessment of adverse events of Gliclazide MR are presented in comparison with both other sulfonylureas and glucose-lowering drugs of other classes.

The growing incidence of diabetes mellitus requires the optimizing of existing approaches and searching for new ones to treat this disease. It is necessary to study the features of other regulators that play a significant role in the process of glucose uptake by cells, along with the insulin resistance caused by defects in the molecular mechanisms of insulin action. Galanine, a neuropeptide of 29 (30 in humans) amino acids, is involved in a large number of different vital functions, including regulating energy metabolism in the cell. Galanine interacts with three G protein-coupled receptors, GAL1, GAL2, and GAL3, and transmitting signals through several transduction pathways, including cAMP/PKA inhibition (GAL1, GAL3) and phospholipase C (GAL2) stimulation. Agonists and antagonists of galanine receptor subtype GalR1-3 can be used as intended therapeutic targets to treat various human diseases. We accumulated more data that prove the importance of the galanine peptide regulator in the etiology of impaired glucose uptake by insulin-dependent tissues. The review considers such effects of galanine, as inhibition of insulin synthesis, activation of expression and translocation to the plasma cell membrane of the glucose transporter GLUT4, increase of PPAR-g level, and decrease in duodenal hyper-contractility. These data confirm the importance of research to find an effective antidiabetic drug among the synthesized analogs of galanine.

Diabetic osteoarthropathy is one of the most difficult complication of diabetes mellitus, requiring the cooperation of a many of specialitys, including traumatologists - orthopedists. However, there is no single approach to the choice of orthopedic treatment tactics for this group of patients. From 2015 to 2018 inclusive, there were 35 patients with diabetic osteoarthropathy that received conservative or surgical orthopedic treatment. 11 patients received conservative orthopedic treatment; 24 patients received surgical treatment. A total of 26 surgical interventions were performed. Two types of surgical interventions were performed: 1) resection of the protruding fragment of one or another bone of the tarsus - 12 operations 2) reconstructive surgery aimed at correcting gross deformation of the middle and / or hindfoot - 14 operations. Along with general clinical examination, all patients underwent orthopedic examination, determining the degree of blood supply disturbance. A differentiated approach to choosing the method of orthopedic treatment of the presented group of patients allowed to restore limb supportability, ensure stability in the ankle joint and joints of the middle foot, create conditions for healing and prevention of relapse of the ulcer. The experience gained allowed us to offer indications for a particular method of orthopedic treatment of foot deformities in diabetic osteoarthropathy, depending on the stage of the pathological process, its location, the severity of the deformation, and the clinical course of this pathology.