The role of neurohumoral factors in the persistence of aseptic bone inflammation in patients with diabetic neuroosteoarthropathy

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot foot) is a relatively rare complication of diabetes mellitus (DM), which can lead not only to impaired support function of the lower limb in such patients, but also to high amputation. DNOAP is characterized by persistent aseptic inflammation of the bone structures of the foot, which creates significant ­difficulties in planning therapeutic measures. In the medical literature, there are data demonstrating the role of individual ­cytokines and neurohumoral factors in the prolongation of the inflammatory process in diabetes, however, there are currently very few studies that determine reliable markers of aseptic inflammation in DNOAP.AIM: To study the effect of neurohumoral factors and advanced glycation end products on the activity of aseptic inflammation in the bone structures of the foot in patients with type 2 diabetes mellitus (DM2) and diabetic neuroosteoarthropathy.MATERIALS AND METHODS. The study included 88 patients with type 2 diabetes (45 men, 43 women). Group 1 consisted of patients with DM2 and inactive DNOAP (n= 43), group 2 (n= 45) consisted of patients with DM2 and distal diabetic neuropathy without osteoarticular pathology. The diagnosis of diabetic neuropathy was based on the analysis of the clinical picture and indicators of peripheral sensitivity. Diagnosis of DNOAP and determination of its stage was based on clinical data, the results of infrared thermometry and radiology tests of the foot bones. General clinical assessment was used, radiology tests (X-ray, MRI), evaluation of CRP, calprotectin, copeptin, glutathione peroxidase 1 (GP1).RESULTS. According to the results of examination and palpation of the feet, as well as the analysis of the temperature gradient of the skin of the affected and contralateral limb (infrared thermometry), DNOAP was detected and the stage of this complication was determined. The diagnosis of the chronic stage of DNOAP was confirmed by the results of MRI and the clinical picture (no difference in skin temperature on the symmetrical areas of the feet). According to the results of laboratory analysis, a statistically significant difference in copeptin values was revealed — in group 1 — 0.232 µg/ml [0.147; 0.342], in group 2 — 0.115 µg/ml [0.065; 0.203] (p>0.05) and CRP — in group 1 — 7.113 mg/l [2.453; 16.505], in group 2 — 2.187 mg/l [1.131; 5.567] (p>0.05), leukocyte levels in the groups did not differ significantly: group 1 — 7.86 [6.40; 9.00]*10^9, group 2 — 7.00 [6.00; 8.15] (p>0.05). There was a trend towards an increase in the level of calprotectin and glutathione peroxidase-1 in the DNOAP group, however, the differences were not significant. calprotectin — in group 1 — 1.948 [1.229; 2.969], in group 2 — 1.692 [1.16; 2.514] μg/ml and glutathione peroxidase-1 in group 1 — 24.72 [20.1; 31.82], in group 2 — 22.98 [18.94; 31.2] ng/ml.CONCLUSION. In the study, statistically significant differences were obtained in the levels of copeptin and C-reactive protein: in patients with DNOAP, their values were significantly higher, which indicates the persistence of the aseptic inflammatory process in the bone tissue of patients even in the chronic stage of DNOAP. These data may help in deciding whether to use one or another method of unloading the affected joints, which will affect the clinical prognosis. The study of neurohumoral markers of arthropathy in the blood serum of patients with DM2 is carried out for the first time, and therefore it is difficult to compare with the results of other authors. It can be assumed that copeptin and CRP are significant markers of persistent inflammation of the osteoarticular structures of the foot in DNOAP

Immunohistochemical features of the bone tissue of the lower extremities in patients with type 2 diabetes mellitus

Background: Diabetic neuroosteoarthropathy is a serious disabling complication of diabetes mellitus, which, in the absence of timely correct treatment, can lead to high amputations of the affected limb. At present, the reasons and mechanism of the development of Charcot’s foot are not completely clear. It is extremely important to determine the pathophysiological mechanisms of DNOAP formation and to search for reliable markers-predictors of this pathology.Aim: To study the immunohistochemical characteristics of the bone tissue of the lower extremities in patients with diabetic neuroosteoarthropathy in comparison with patients with diabetes mellitus without this pathology.Materials and methods: During the foot surgery, a bone fragment of the foot was harvested for immunohistochemical study of receptor markers for PINP, PIIINP, and RAGE in the group of patients with DNOAP compared with the control group.Results: The study included 20 patients with type 2 diabetes mellitus and were divided into 2 groups: 10 patients with DNOAP made up group 1, 10 patients without DNOAP — group 2.Patients in both groups were comparable in AGE, experience with type 2 diabetes, and glycemic control.During the immunohistochemical study, a significant increase in the staining intensity of receptor markers for PINP, PIIINP, and AGE was recorded in the group of patients with DNOAP compared with the control group (p <0.05).Conclusion: For the first time, an immunohistochemical study of markers of bone resorption and AGE was carried out in persons with DNOAP. The results obtained indicate impaired collagen formation and, as a consequence, impaired bone formation and bone resorption in patients with DNOAP: in group 1, a statistically significant increase in the expression of PINP, PIIINP, and RAGE was revealed

Investigations of Structural-Functional Aspects of Epizootic Process in Natural Plague Foci in Siberia

Comprehensively studied have been structural elements of ecosystems of Siberian natural plague foci, as well as levels of integration among epizootic process components, and ways of their functional interaction. Application of the complex approach to the surveillance over structural-functional elements of the parasitic system along with investigations of epizootic process dynamics has provided for identification of peculiarities as regards epizootics development, transformation and evolution of population and carrier/vector coenosis structure in time and space. Revealed is the genetic diversity of plague microbe circulating within the bounds of separate foci and zones of focality. Determined is a long-lasting anti-epidemic effect (more than 20 years) of the field desinsection in the Saglinsk meso-focus of the Tuva natural plague focus

Epizootiological-and-Epidemical Situation on Tularemia in the South of Far East Region during the Period of River Floods

Carried out were epizootiological studies of the flooded areas of the Amur Region, the Khabarovsk territory, and the Jewish autonomous region in order to investigate the situation on tularemia in view of the river floods in August-September, 2013. Involved were specialized anti-epidemic teams from Irkutsk Research Anti-Plague Institute for works at the site of emergency. Therewith, analysis of the data of the epizootiological examination of the territories obtained in cooperation with specialists from the Rospotrebnadzor local Centers of Hygiene and Epidemiology, and results of laboratory investigations with application of bacteriological, immu­no­bio­logical and molecular-genetic methods indicated insignificant epizootic and epidemic activity of the natural tularemia foci. Given is the conclusion on epizootiological-epidemiological condition for tularemia in the flooded areas of the Amur River region and a short-term epizootiological forecast for 2013-2014, as well as recommendations concerning stabilization and improvement of epidemiological conditions in the region

КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ ПО ДИАГНОСТИКЕ И ЛЕЧЕНИЮ СИНДРОМА ДИАБЕТИЧЕСКОЙ СТОПЫ

The guideline presents modern classification, diagnostic algorithms and protocols of complex treatment of various forms of diabetic foot syndrome. The recommendations are intended for use by a wide range of professionals involved in the treatment of patients with this pathology.В клинических рекомендациях представлены современные классификации, алгоритмы диагностики и протоколы комплексного лечения различных форм синдрома диабетической стопы. Рекомендации предназначены для широкого круга специалистов, занимающихся лечением пациентов с данной патологией

Diabetes mellitus type 2 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.&nbsp

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 10th edition

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Grou

Vozmozhnosti primeneniya lipidnokolloidnykh povyazok v kompleksnoy terapii bol'nykh s neyropaticheskoy formoy sindroma diabeticheskoy stopy

Лечение хронических раневых дефектов стоп у больных сахарным диабетом (СД) является, на сегодняшний день, одной из актуальных проблем не только эндокринологии, но и хирургии. Распространенность подобных поражений, по мнению различных авторов, составляет от 4 до 15 % (1, 2). По данным американских исследователей (3, 4) больные с диабетическими трофическими язвами стоп составляют 6% всех госпитализированных с СД, а срок их пребывания в стационаре на 59% больше, чем у лиц без нарушений целостности кожных покровов. Локализация трофических нарушений на конечностях зависит, в основном, от этиологических факторов. По данным анализа организации амбулаторной медицинской помощи в США (2) чаще диагностируются раневые дефекты тыльной и подошвенной поверхностей пальцев, подошвенной поверхности в зоне проекции костей предплюсны и плюсны. Последние характеризуются наиболее тяжелым течением и худшим клиническим прогнозом (2). Необходимо подчеркнуть, что деформации стоп и нейропатия являются наиболее значимыми факторами развития хронических раневых дефектов мягких тканей нижних конечностей. Хронические раны (или трофические язвы) характеризуются дефектным ремоделированием экстра-целлюлярного матрикса, нарушением реэпителизации и длительной воспалительной фазой (5, 6). Эпидермис не может мигрировать в раневую зону, идёт гиперпролиферация грануляционной ткани в краях дефекта, которая мешает нормальной клеточной миграции по раневому ложу. Диабетические язвы стоп считаются «замершими» на фазе пролиферации (7). Важную роль в торможении заживления ран у больных СД играет раневой экссудат. Экссудат хронических ран (в том числе и трофических язв у больных с синдромом диабетической стопы) биохимически отличается от такового в острой ране: он замедляет или даже блокирует пролиферацию кератиноцитов, фибробластов и эндотелиальных клеток и тем самым тормозит заживление. Отделяемое хронической раны характеризуется повышенной протеолитической активностью. Более высокая концентрация матриксных металлопротеиназ и сериновых протеаз приводит к разрушению или изменению компонентов матрикса, необходимых для реэпителизации. Фактором, тормозящим заживление, является и способность макромолекул экссудата хронической раны связывать факторы роста. Все выше сказанное определяет необходимость разработки и широкого клинического внедрения новых средств местного лечения ран, которые обладали бы способностью нейтрализовать деструктивные свойства экссудата, одновременно препятствуя пересыханию раневой поверхности. Одним из таких современных средств местного лечения хронических ран является Cellosorb Ag (Urgo, Франция). Данная повязка производится с использованием липидо-коллоидной технологии, что позволяет поддерживать влажную среду в ране, а способность к вертикальной абсорбции препятствует накоплению избытка экссудата и мацерации окружающих здоровых тканей. Наличие в составе повязки ионов серебра определяет ее антисептические свойства, что обеспечивает быстрое и длительное антибактериальное действие. В литературе имеется ряд зарубежных публикаций касающихся опыта применения липидоколлоидных повязок у больных с венозными язвами голеней. Результатов использования данных средств местного лечения ран у больных СД и синдромом диабетической стопы в доступной нам литературе обнаружено не было. В отделении терапевтических и хирургических методов лечения диабетической стопы ФГУ ЭНЦ применение липидо-коллоидных повязок указанного выше производителя началось в 2009 г. В настоящей публикации мы приводим клинический случай использования Cellosorb Ag в комплексной терапии пациента с нейропатической формой синдрома диабетической стопы

Sovremennye podkhody k vedeniyu bol'nykh s neyro-ishemicheskoy formoy sindroma diabeticheskoy stony

Несмотря на очевидные успехи современной диабетологии, проблема поражения нижних конечностей у пациентов с диабетом как 1, так и 2 типов сохраняет свою актуальность. Проведенные в ряде стран эпидемиологические исследования показали, что различная патология стоп и голеней, и в первую очередь синдром диабетической стопы, является важной медико-социальной и экономической проблемой. На основании обследования больших групп пациентов показано, что наиболее значимыми факторами риска развития хронических раневых дефектов стоп при СД является потеря чувствительности, развивающаяся на фоне диабетической нейропатии и снижение периферического артериального кровотока. Вместе с тем, некоторые исследователи не нашли прямой зависимости риска развития поражений конечностей от уровня компенсации углеводного обмена. Также одним из значимых факторов риска является деформация стопы