Lesions of the lower extremities in diabetes mellitus are a complex and urgent problem of modern medicine. The high prevalence of diabetes mellitus, significant difficulties in timely diagnosis, differential diagnosis and the choice of therapeutic tactics to preserve the supporting function of the limb determine the difficulties in managing diabetic patients. Over the past decades, significant changes have occurred in the structure of specialized medical care for diabetic foot patients which has significantly reduced the number of high amputations, improved the quality and life expectancy of patients. The article presents the results of the long-term experience of the Diabetic Foot department in the treatment of diabetic foot patients.

This post hoc analysis of an A Toujeo® Observational Study (ATOS) aims to evaluate the real-world effectiveness and safety of insulin glargine 300 U/ml (Gla-300) in high-risk subgroups of insulin-naïve people with type 2 diabetes (PwT2D) from multiple geographical regions (Asia, the Middle East, North Africa, Latin America, and Eastern Europe). In these post hoc analyses of ATOS, a real-world, 12-month, prospective study included 4422 insulin-naïve adults (age ≥ 18 years) with type 2 diabetes (T2D) uncontrolled (HbA1c > 7

AIMS:To evaluate the immunogenicity, efficacy, and safety of a biosimilar insulin glulisine candidate (T-Glu) compared to the reference product (R-Glu) in patients with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS:In this phase III, randomised, open-label trial, adult patients with T1DM received either T-Glu or R-Glu by prefilled pens as their bolus insulin for 26 weeks. The primary outcome was the proportion of patients with an immune response at Week 26. Secondary endpoints included changes in glycaemia control parameters, insulin dose stability, treatment satisfaction, and other immunogenicity and safety outcomes. RESULTS:By Week 26, the immune response persisted in 16% of patients in the T-Glu group and 24% in the R-Glu group (p > 0.05), confirming similar immunogenicity. HbA1c reduction at Week 26 compared to baseline was similar between groups, with a mean change of 0.53% ± 1.19% in the T-Glu group and 0.38% ± 1.46% in the R-Glu group (mean difference: -0.15%, 95% CI: -0.50 to 0.20), demonstrating non-inferiority (according to a predefined margin of 0.4%). Fasting plasma glucose levels and the seven-point glucose profile showed no significant differences between groups (p > 0.05). Insulin dose remained stable throughout the study, and treatment satisfaction scores improved comparably in both groups (p > 0.05). The total number of AEs was similar, and hypoglycaemia was more frequent in the R-Glu group (p < 0.001), with no new safety concerns identified. CONCLUSIONS:T-Glu demonstrated similar immunogenicity, efficacy, and safety to R-Glu in adults with T1DM, supporting its use as a biosimilar insulin glulisine. CLINICALTRIALS:gov: NCT07070752.

According to modern concepts, Charcot’s neuro-osteoarthropathy (Charcot’s foot) is considered as an aseptic inflammatory process in individuals with distal polyneuropathy, which leads to damage to bones and joints. Most often, Charcot’s foot is formed in patients with diabetes mellitus (DM) and affects the foot and ankle joint. Diabetic neuroosteoarthropathy (DNOAP) is divided into active and inactive stages. The typical clinical picture of the active stage of diabetic neuroosteoarthropathy is edema and hyperemia of the affected foot, with a temperature gradient of more than 2 °C compared with an unaffected foot. The nonspecific clinical picture of the active stage of diabetic neuroosteoarthropathy makes it difficult to diagnose and often leads to the need for differential diagnosis of the active stage of diabetic neuroosteoarthropathy and osteomyelitis, which is one of the most difficult issues in clinical practice. Early detection of these conditions is crucial, since treatment of the active stage of diabetic neuroosteoarthropathy can prevent irreversible deformity of the foot, and detection of osteomyelitis will allow timely antibiotic therapy. Signs of changes in bone and foot structures in the active stage of diabetic neuroosteoarthropathy in images obtained by computer X-ray, magnetic resonance and emission tomography may be similar to signs of osteomyelitis, which determines the importance of choosing an imaging method when examining a patient and developing an effective algorithm for early diagnosis of DNOAP. In this review, the main attention will be paid to the distinctive features of the active stage of diabetic neuroosteoarthropathy and osteomyelitis when using imaging research methods.

The increase in the number of patients with type 2 diabetes mellitus (T2D) and mortality among them forces us to look for ways to optimize T2D treatment. At the same time, more than half of patients with an established diagnosis do not reach the glycemic targets and require intensification of therapy. Due to the progressive deterioration of the glycemic status, almost one in five T2D patients requires insulin therapy (IT), and over time, IT intensification with titration of the dose of insulin. This approach is limited by a few adverse effects such as: an increased risk of severe hypoglycemia, weight gain, decreased sodium excretion, which means fluid retention in the body, and the patient’s unwillingness to carry out complex therapy regimens. The addition of sodium-glucose cotransporter 2 (SGLT2i) inhibitor with an insulin–independent mechanism of action to the treatment is aimed to solve the problem of optimizing glycemic control in this category of T2D patients. The purpose of this network meta-analysis (NMA) was to indirectly compare the efficacy and safety of SGLT2 inhibitors added on top of insulin in T2D patients. The analysis included randomized clinical trials in which dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and ertugliflozin were prescribed as SGLT2i. The primary endpoint was a change in glycated hemoglobin (HbA1c), and the secondary endpoints were changes in a mean of fasting plasma glucose, body weight and blood pressure, as well as the mean change in daily dose of insulin. The analysis of safety data included a comparative assessment of the incidence of hypoglycemia, reproductive tract and urogenital infections, and hypovolemia. The results of the conducted NMA demonstrate the comparable effectiveness of various SGLT2i regarding managing of glycemic status in T2D patients receiving insulin, along with commensurate safety and tolerability of therapy.

The aim of the study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of T-glu (GP40321, test drug), and reference insulin glulisine in a hyperinsulinemic-euglycemic clamp procedure. During this study, 34 healthy male volunteers underwent the hyperinsulinemic-euglycemic clamp procedure following subcutaneous 0.3 U/kg injection of T-glu or reference insulin glulisine in a randomized, double-blind, crossover study. Plasma glucose levels were monitored every 5 minutes for 8 hours. Glucose infusion rate adjustment was based on the blood glucose measurements. Evaluation of PD was performed using the glucose infusion rate values, while PK was calculated using insulin concentrations measured via enzyme-linked immunosorbent assay. The study results showed that the 90% CI for the geometric mean ratios of primary PK and PD of T-glu and reference insulin glulisine were within 80%-125% comparability limits, and that the safety profiles were comparable. PK, PD, and safety similarity of T-glu and reference insulin glulisine was demonstrated.

Introduction: Initiating Gla-300 has shown to improve treatment satisfaction in PwT2D in RCT and real-world studies. ATOS, a 12-month prospective observational global study showed that initiating Gla-300 in insulin-naïve PwT2D resulted in improved glycemic control and low hypoglycemia rates. Methods: This post-hoc analysis evaluated meaningful improvements in Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores with glycemic parameters. Data was collected at baseline, months 3, 6 and 12, and based on distribution-based method (0.5 SD of baseline DTSQs score) for meaningfulness, percentage of responders was determined. Results: Total, 3801 participants completed the questionnaire. At baseline, mean ± SD age was 57.7 ± 10.5 years, duration of diabetes was 10.2 ± 6.2 years and DTSQs total treatment satisfaction score 21.7 ± 7.4. Percentages of responders (improvement in DTSQs total score ≥4 points) were 60.2% at month 3 and 75.2% at month 12. A decrease in perceived frequency of hyper/hypoglycemia and higher reduction in mean HbA1c and FPG from baseline to month 12 were also observed for responders vs. non-responders (Table). Conclusion: The majority of insulin naïve PwT2D initiating Gla-300 reported meaningful increase in treatment satisfaction and decrease in perceived frequency of hyper/hypoglycemia, associated with decreased HbA1c. Disclosure S.B. Harris: Consultant; Abbott. Research Support; Boehringer-Ingelheim. Consultant; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company, Novo Nordisk, Sanofi. Research Support; Novartis AG. Consultant; Bayer Inc. N. Khan: None. A. Tirosh: Advisory Panel; Novo Nordisk. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Sanofi, GlaxoSmithKline plc, Medtronic. Consultant; Radella Pharmaceuticals. J. Kesavadev: None. H. Vargas-Uricoechea: Speaker's Bureau; Abbott, Sanofi-Aventis U.S. A. Roborel de Climens: Stock/Shareholder; Sanofi. H. Baghous: Other Relationship; Sanofi, Novo Nordisk. F.J. Snoek: Advisory Panel; Abbott, Sanofi, Eli Lilly and Company, Roche Diabetes Care. M.N. Mabunay: None. N. Grulovic: Employee; Sanofi. V. Corp dit Genti: Employee; Sanofi. J. Msihid: Employee; Sanofi. Stock/Shareholder; Sanofi. G.R. Galstyan: None. Funding Sanofi

AIM: to assess proliferation and migration of keratinocytes at the nonhealing edges of neuropathic wounds.MATERIALS AND METHODS: 25 patients with neuropathic ulcers and 5 patients without diabetes with decubitus were enrolled. Diabetic foot (DF) patients were underwent to standard treatment including debridement, atraumatic dressing, offloading, antibacterial therapy if it needs. Severity of peripheral neuropathy was assessed according to the NDS scale. Histo­logical (hematoxylin and eosin) and immunohistochemical (Ki-67 , α7nAChR markers) examination of wound edge were done during treatment (0, 10, 24 days).RESULTS: All patients have severe neuropathy according to NDSm (>8). The average size of DF ulcers before and on 10th day of treatment was of 4 cm2 and 2,5 cm2, respectively (p<0,004). Neuropathic ulcers were characterized by hyperproliferative epidermis. Mitotically active keratinocytes reside throughout the suprabasal layers. Ki-67 expressed all layers of the epidermis, but a greater staining density was detected in the basal layer. The density of a7nAChR-positive cells increased from 0 to 24 days (p=0,031).THE CONCLUSION: The data shows that neuropathy is one of the possible mechanisms of keratinocyte cell cycle disruption: proliferative activity and ability to migrate. Identification of new signaling pathways regulating the physiological repair of tissues and the study of their disorders in diabetes mellitus opens the prospect of developing an optimal therapeutic strategy.

The number of patients with diabetes mellitus (DM) has been progressively increasing worldwide over the past decades, and many international organizations consider DM as a public health emergency of the 21st century.Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD) in DM and is characterized by a high risk of limb loss without revascularization. Traditional treatment tactics include open and endovascular revascularization surgical techniques. However, in patients not eligible for revascularization and in cases where performed surgical treatment performed has been ineffective, there are almost no therapeutic alternatives, often leading to amputations and death. As of today, one of the newest non-surgical treatment options is cell therapy. Among different cells, mesenchymal stromal cells (MSCs) are potentially one of the most prospective for use in this patient population.This article provides an overview of clinical trials using cell therapy in patients with CLI.To analyze publications, electronic databases PubMed, SCOPUS, ClinicalTrials, and ScienceDirect were searched to identify published data from clinical trials, research studies, and review articles on cell therapy for critical lower extremity ischemia. After the search, 489 results were received.As a result of systematic selection, 22 clinical trials were analyzed.According to the analyzed literature data, the use of cell products in this category of patients is effective and safe. Cell therapy can stimulate the formation of new vessels and enhances collateral circulation; it is also reported improved distal perfusion, increased pain-free walking distance, decreased amputation rates, and increased survival rates.Nevertheless, further study of the potential use of this category of drugs is needed.

Diabetic neuropathy is one of the most common diabetes mellitus complications associated with mediocalcinosis of the lower extremities, a significant decrease in feet bone mineral density, and a high incidence of cardiovascular disease. In most cases, calcium-phosphorus metabolism changes occur in patients with diabetic neuroarthropathy, or Charcot foot, when we can observe feet local osteoporosis, which in 90% of cases associated with a vessel’s calcification of the lower extremities in the majority of diabetes population. A large number of studies presented literature have demonstrated that patients with Charcot foot can have accelerated bone metabolism and increased bone resorption. Patients with Charcot foot often have crucial abnormalities in the calcium-phosphorus parameters, bone metabolism, and levels of vitamin D and its metabolites. In addition, the duration of diabetes mellitus, the degree of its compensation widely affects the development of its micro- and macrovascular complications, which could also accelerate the development of mineral and bone disorders in these types of patients. Multifactorial pathogenesis of these disorders complicates the management of patients with a long and complicated course of diabetes mellitus. This review discusses the peculiarities of vitamin D metabolism, the importance of timely diagnosis in phosphorus-calcium disorders, and the specifics of therapy in these patients. Special attention is paid to the timely diagnosis of the Charcot’s foots acute stage based on the bone marrow edema by MRI evaluation and the possibility of reducing the immobilization period.

Diabetes mellitus remains one of the main socially significant health problems worldwide. Glycemic control plays a key role in the prevention of all complications of diabetes mellitus. One of the most important factors in the overall control of glycemia in patients with both type 1 and type 2 diabetes mellitus is postprandial glucose levels, as a leading risk factor for delayed vascular complications. Modern possibilities for controlling postprandial glycemia include the use of not only ultrashort insulin preparations, but also ultrafast action. One of the superfast insulin preparations available today is the drug Lumzhev ® (inLisFast), which contains lyspro insulin as an active ingredient. A number of studies on the comparative pharmacokinetics and pharmacodynamics of inLisFast compared with insulin lispro consistently demonstrate a shift in the pharmacokinetic and pharmacodynamic profile to the left, which indicates faster absorption, an increase in early insulin exposure and a decrease in late insulin exposure. inLisFast provides flexibility in the regulation of food intake, which can play a significant role in optimizing glycemic control and improving the quality of life of patients with diabetes.

The article presents the result of our own observation of the patient with a poor control of type 2 diabetes mellitus (DM) for a long period, complicated by obliterating atherosclerosis of the arteries of the lower extremities, Menckeberg’s sclerosis and chronic ischemia threatening loss of the lower extremity (CLLI). A feature of the clinical manifestation are complications associated with potentially regional (angiosomal) ischemia of the foot, as well as variant anatomy, represented by hypoplasia of the vascular lower leg in the patient. The clinical consequences of vascular calcification due to long-term decompensation of carbohydrate metabolism and the development of diabetic distal polyneuropathy (DDP) led to falsely high values of the cuff test in the patient. Disadvantages of non-invasive methods for diagnosing limb ischemia and advantages of the complex application of tests for diseases of the arteries of the lower extremities are discussed. Using WIFI classification according to the degree of ulceration, the degree of ischemia, and the degree of infection on the foot (Wound, Ischemia and Foot Infection), the tactics of managing the patient are presented. The important role of ultrasonic duplex scanning (USDS) in the visualization of the arteries of the legs and feet in patients with DM is substantiated. The importance of a multidisciplinary approach in the management of a comorbid patient with type 2 diabetes and CLTI is emphasized.

The prevalence of type 2 diabetes mellitus (T2DM) is steadily increasing. Currently, highly effective modern classes of glucose-lowering medications (GLM) have largely put non-drug interventions on the back burner. At the same time, the maximum realization of the potential of GLM is possible only if the patient's lifestyle is changed. If we look at the publication activity in this area, a significantly more number of scientific articles are devoted to the nutrition therapy, and physical activity (PA) has received much less attention. This publication discusses issues such as the classification of physical exercises, benefits of regular PA, principles of designing physical therapy classes, recommendations for PA to the patients with T2DM, as well as barriers to expansion of PA and possible ways to overcome them.

An erratum on « Insufficiency/deficiency of vitamin B12 in patients in the endocrinological practice» by Natalya G. Mokrysheva, Marina V. Shestakova, Alexander S. Ametov, Mikhail B. Antsiferov, Igor G. Bakulin, Tatiana V. Vavilova, Gagik R. Galstyan, Tatiana Y. Demidova, Fatima K. Dzgoeva, Tatiana L. Karonova, Elena A. Lukina, Ashot M. Mkrtumyan, Rodion V. Ponomaryov, Natalia A. Suponeva, Olga Y. Sukhareva, Minara S. Shamkhalova (2024). Diabetes mellitus. 27(3). doi: 10.14341/DM13181An error was made in the list of authors: Nina A. Petunina was not indicated as author of this article. The correct list of authors: Natalya G. Mokrysheva, Marina V. Shestakova, Alexander S. Ametov, Mikhail B. Antsiferov, Igor G. Bakulin, Tatiana V. Vavilova, Gagik R. Galstyan, Tatiana Y. Demidova, Fatima K. Dzgoeva, Tatiana L. Karonova, Elena A. Lukina, Ashot M. Mkrtumyan, Nina A. Petunina, Rodion V. Ponomaryov, Natalia A. Suponeva, Olga Y. Sukhareva, Minara S. Shamkhalova.The identifier in the ORCID system for F.K. Dzgoeva was also indicated incorrectly. The correct link is: https://orcid.org/0000-0002-0533-7652.The editorial board apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.

On March 20, 2024, an interdisciplinary meeting of the Expert Council on the current problem of B12 insufficiency/deficiency and the prevalence of this condition among endocrine patients was held at the Endocrinology Research Centre (Moscow). The purpose of the meeting was to assess the role of B12 deficiency in reducing the quality of life of patients of different groups and to outline a strategy for the management of patients with vitamin B12 insufficiency/deficiency by endocrinologists.The resolution of the expert council was developed by leading specialists in various specialties.

Diabetes is disease of both the endo- and exocrine parts of the pancreas. Pancreatic exocrine insufficiency (PEI) can occur in every 2–3 patients with diabetes and affect not only the quality, but also life expectancy. At the same time, the diagnosis and treatment of PEI is not getting enough attention. The endocrinologist, as the main specialist leading patients with diabetes, can diagnose and treat patients with pancreatic exocrine insufficiency and diabetes using adequate doses of pancreatic enzyme replacement therapy (PERT).

The manual for healthcare professionals and nurses to be used for the education of type 2 diabetes mellitus patients receiving insulin therapy was developed by the employees of Endocrinology Research Centre in accordance with clinical guidelines, WHO recommendations and is based on the principle of structuring patient education. The manual contains a plan of classes and topics necessary for patients. The content of the classes is presented in a language understandable to the patients. Specific medical terminology is not used. Education of patients using the proposed program can be carried out both in the in-patients hospital and on an outpatient basis, depending on the conditions available in a particular medical institution. Approved and recommended for use by the Russian Association of Endocrinologists.