Of the many clinical phenotypes of obesity, the most prevalent are metabolically “healthy” (MHO) and metabolically “unhealthy” (MUO) obesities, the latter being associated with a range of comorbidities, including type 2 diabetes mellitus (T2DM). The underlying causes of different obesity phenotypes and the mechanisms of conversion of one phenotype into another have yet to be fully elucidated. However, increasing evidence suggests the key role of low-grade metabolic inflammation (metaflammation) in the pathogenesis of obesity and metabolic dysfunction. The review presents a comprehensive description of changes in immune cell populations and pro-inflammatory mediators, as well as a detailed comparative mapping of the adipose tissue immune landscape during MHO/MUO transition. Based upon a conceptual model for the intensification of metaflammation during MHO progression and conversion to MUO, a pattern of dynamical changes that accompany MHO/MUO transition is described. Though many parameters demonstrate significant differences in multiple cross-sectional and some longitudinal studies, only a few of them (CRP, IL-6, IL-17A, absolute counts of leukocytes and neutrophils) meet the criteria of a validated biomarker in clinical setting. A lack of standardization in MHO definition and heterogeneity in the severity of MUO make the search for predictive biomarkers a challenge. The review also discusses the mechanisms underlying metabolic memory and the incomplete reversibility of metabolic disturbances after bariatric surgery.

One-anastomosis gastric bypass (OAGB) represents a novel less invasive bariatric surgery technique that can significantly improve systemic metabolism and adipose tissue health in patients with type 2 diabetes mellitus (T2DM). Previously, we demonstrated that T2DM impairs proliferation and differentiation of adipose tissue progenitors. Obese patients with T2DM (n = 10) underwent clinical examination and subcutaneous fat biopsy during bariatric surgery and in 6 mo. Adipose-derived stem cells (ADSCs) were isolated by enzymatic method. Cell proliferation was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and immunocytochemistry. Adipogenesis and thermogenesis were assessed by confocal microscopy. Adipocyte metabolism was estimated by radioisotope tracing. Western blotting was used to quantify protein expression. Median weight loss after OAGB was 40 kg. OAGB resolved hyperinsulinemia and stimulated insulin sensitivity with changes in homeostatic model assessment of insulin resistance and M-index up to twofold. Bariatric surgery significantly influenced properties of ADSC adipocytes: there were an increase in ADSC proliferation, decrease in white adipogenesis, activation of white and beige adipocyte lipid droplet fragmentation, activation of thermogenesis, and inhibition of lipogenesis. OAGB promotes weight loss and insulin sensitivity and changes regenerative potential of ADSC. Enhanced ability of ADSC to proliferate and differentiate into thermogenic adipocytes with reduced activity of lipogenesis may prevent weight gain after bariatric surgery.NEW & NOTEWORTHY Today, bariatric surgery remains the most effective instrument for weight loss, glycemic control, and type 2 diabetes combat. Bariatric surgery causes mild stimulation of ADSC proliferation and suppresses white adipogenesis. ADSC-derived adipocytes exhibited lipid droplet fragmentation, activation of thermogenesis, and inhibition of lipogenesis. Thus, enhanced ability of ADSC to proliferate and differentiate into thermogenic adipocytes with reduced activity of lipogenesis may support energy expenditure and prevent weight gain after bariatric surgery.

Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemic control are bariatric surgery (BS) and pharmacotherapy. The aim of our study is to evaluate changes in adipose tissue secretome after BS and semaglutide injections. 17 patients with T2DM were examined before and 6 months after BS or semaglutide therapy. The examination protocol included anthropometry, clinical biochemistry, insulin resistance evaluation and collection of subcutaneous adipose tissue biopsies. Adipose derived stem cells (ADSC) were isolated from biopsies according to a standard enzymatic protocol and differentiated into white and beige adipocytes. Adipogenesis and thermogenesis were assessed by confocal microscopy. Secretome of adipocytes and cytokines plasma levels were analyzed using a MILLIPLEX panel. Following BS and semaglutide therapy, a decline in BMI, total fat content, HbA1c, and fasting blood glucose was observed. Insulin sensitivity increased only 6 months after BS. Semaglutide therapy resulted in the elevation of angiogenic and proinflammatory cytokines in adipocyte secretory profile. After BS we also detected the increase in proinflammatory cytokines both in adipocyte secretome and in plasma levels. However, the adipocyte secretome subsequent to bariatric surgery (BS) exhibited a reduced proinflammatory response in comparison to that observed following semaglutide therapy. The effect of semaglutide injections directly on adipose tissue can change the function of ADSC, making them more angiogenic and adipogenic. A decrease in BMI, HbA1c and insulin resistance is achieved to a significant extent only after BS. BS-induced T2DM remission is related to lower pro-inflammatory secretion from adipocytes as compared to semaglutide. The regulation of inflammation in adipocytes may serve as a potential mechanism underlying BS-induced T2DM remission.

Background. Diabetes mellitus (DM) and obesity are diseases that lead to systemic complications that shorten life expectancy and reduce quality of life. Treatment and control of these diseases can reduce the risk of complications. However, existing lifestyle change programs and drug therapy have limited effectiveness, and therefore, the search for new methods of treating diabetes and obesity is still relevant. Aim. To determine the effectiveness of an oral care product (OCP) containing curcumin, thyme, and catechins in patients with obesity and type 2 DM (T2DM) in reducing appetite, changing taste preferences, and improving oral hygiene. Materials and methods. The study patients were divided into three groups: those with obesity and T2DM, those with obesity without T2DM, and a control group of persons without obesity and carbohydrate metabolism disorders. All participants were recommended to irrigate the oral cavity 3 times a day for 20–30 with an OCP containing 0.25% curcumin, 0.05% thyme, and 0.05% catechins 30 minutes before meals for 30 days. Initially and after a month of daily use of the OCP, food preferences were assessed based on the NHANES Food Questioner and the oral cavity condition. Results. The study included 67 patients. According to the questionnaire, the consumption of the following products decreased in all three groups of subjects: red meat, sausages, fast food, cookies, tomato juice, beer, red wine, and butter. Hyperemia, edema, ulcerative defects, and oral dryness decreased in obese patients with and without T2DM. Conclusion. OCP use decreased appetite and changed taste preferences and also significantly improved the condition of the oral mucosa and gums in obese patients with and without T2DM. Further studies are needed to assess the therapeutic potential of OCP with curcumin, thyme, and catechins in treating obesity and carbohydrate metabolism disorders.

Background: findings from the previously conducted studies indicate altered regulatory mechanisms of calcium and vitamin D metabolism in obese patients and a role for bariatric surgery in regulating vitamin D metabolism; however, the available data is controversial and does not provide an adequate understanding of the subject. Methods: we evaluated serum parameters of vitamin D and mineral metabolism (vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3), vitamin D-binding protein (DBP), free 25(OH)D, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), total calcium, albumin, phosphorus, creatinine, magnesium) in 30 patients referred for bariatric surgery in comparison with 30 healthy volunteers of similar age, sex and baseline 25(OH)D3. Patients were also followed up with repeated laboratory assessments 3 months and 6 months after surgery. During the first 3 months, patients were prescribed high-dose cholecalciferol therapy (50,000 IU per week), with subsequent correction based on the results of the 3-month visit examination. Results: Preoperatively, patients with morbid obesity were characterized by a high prevalence of vitamin D deficiency (median 25(OH)D3 level 11.9 (6.8; 22.2) ng/mL), significantly lower levels of active vitamin D metabolite 1,25(OH)2D3 (20 (10; 37) vs. 39 (33; 50) pg/mL, p < 0.001), lower serum albumin-adjusted calcium levels (2.24 (2.20; 2.32) vs. 2.31 (2.25; 2.35) mmol/L, p = 0.009) and magnesium levels (0.79 (0.72; 0.82) vs. 0.82 (0.78; 0.85) mmol/L, p = 0.043) with simultaneous similar PTH levels (p = 0.912), and higher DBP levels (328 (288; 401) vs. 248 (217; 284) mg/L, p < 0.001). The 25(OH)D3 levels remained suboptimal (24.5 (14.7; 29.5) ng/mL at the 3-month visit and 17.9 (12.4; 21.0) ng/mL at the 6-month visit, p = 0.052) despite recommended high-dose cholecalciferol supplementation. Patients also demonstrated an increase in 1,25(OH)2D3 levels (38 (31; 52) pg/mL at the 3-month visit and 49 (29; 59) pg/mL at the 6-month visit, p < 0.001) without a change in PTH or calcium levels during the follow-up. Conclusion: our results of a comprehensive laboratory evaluation of vitamin D status and mineral metabolism in patients undergoing bariatric surgery highlight the importance of improving current clinical guidelines, as well as careful monitoring and education of patients.

Background: Bariatric surgery is known to induce weight loss and diabetes remission in patients with type 2 diabetes (T2D), but the exact mechanism of glycemic normalization needs to be defined. Methods: The study included patients with BMI ≥ 35 kg/m2, obesity history ≥ 10 years, and planned bariatric surgery. At baseline and 3 and 6 months after surgery, all patients underwent anthropometric measurements, body composition and blood tests (including insulin, glucagon, and incretins during oral glucose tolerance test (OGTT)), and hyperinsulinemic euglycemic clamp tests. Diabetes remission was defined if the person reached HbA1c < 6.5% after surgery and glucose-lowering therapy withdrawal. Results: The study included 86 patients, divided into groups with no diabetes (control group, n = 44) and T2D (n = 42). Most patients with T2D reached normoglycemia at 6 months. BMI and insulin resistance (according to M-index) decreased in T2D group comparably to people without diabetes. At 6 months, people with T2D at baseline had less insulin and GLP-1 secretion and higher glucagon level during OGTT when compared to the control group. Conclusions: We conclude that weight and insulin resistance reduction is sufficient for T2D remission. The absence of insulin, glucagon, and incretin restoration is not crucial for the glucose metabolism in the short-term, but it may explain the relapse of T2D years after bariatric surgery.

Consuming high-calorie and thermally processed foods leads to increased body weight and increased levels of advanced glycation end products (AGE) in the human body. AGE has been shown to contribute to dietary oxidative stress and processes that play a major role in the development of type 2 diabetes mellitus (T2DM). Data obtained from cellular and mouse models indicate that the interaction of AGEs with their receptor, RAGE (receptor for advanced glycation end products), promotes the development of inflammation in adipose tissue (AT) through the activation of pro-inflammatory signaling cascades. In addition, there is new evidence, which shows influence of RAGE on the transformation of AT macrophages into the provoking M1 phenotype, which also promotes the degree of inflammation in AT. Inflammation in AT leads to the development of insulin resistance and, accordingly, T2DM. At the same time, there are also RAGE isoforms that can prevent the start of the inflammatory process. The review is devoted to modern views on the role of AGE-RAGE systems in the development of carbohydrate metabolism disorders in obese people.

The clinical blood metabogram (CBM) was developed to match a tailored analysis of the blood metabolome to the time, cost, and reproducibility constraints of clinical laboratory testing. By analyzing the main blood metabolite groups, CBM offers clinically relevant information about the intake of low-molecular substances into the organism, humoral regulation, liver function, amino acid level, and the lipid and carbohydrate metabolism. The purpose of this work was to investigate the relevance of using the CBM in patients with diabetes mellitus. For this, a CBM was obtained for 18 healthy individuals, 12 individuals with prediabetes, and 64 individuals with type 2 diabetes mellitus, separated into groups according to fasting blood glucose and oral glucose tolerance tests. The results showed that the CBM reveals diabetes-associated metabolic alterations in the blood, including changes in the levels of carbohydrates, ketone bodies, eicosanoids, phospholipids, and amino acids, which are consistent with the scientific data available to date. The CBM enabled the separation of diabetic patients according to their metabolic metabotypes, providing both a general overview of their metabolic alterations and detailing their individual metabolic characteristics. It was concluded that the CBM is a precise and clinically applicable test for assessing an individual’s metabolic status in diabetes mellitus for diagnostic and treatment purposes.

Saturated free fatty acids are thought to play a critical role in metabolic disorders associated with obesity, insulin resistance, type 2 diabetes (T2D), and their vascular complications via effects on the vascular endothelium. The most abundant saturated free fatty acid, palmitate, exerts lipotoxic effects on the vascular endothelium, eventually leading to cell death. Shear stress activates the endothelial AMP-activated protein kinase (AMPK), a cellular energy sensor, and protects endothelial cells from lipotoxicity, however their relationship is uncertain. Here, we used isoform-specific shRNA-mediated silencing of AMPK to explore its involvement in the long-term protection of macrovascular human umbilical vein endothelial cells (HUVECs) against palmitate lipotoxicity and to relate it to the effects of shear stress. We demonstrated that it is the α1 catalytic subunit of AMPK that is critical for HUVEC protection under static conditions, whereas AMPK-α2 autocompensated a substantial loss of AMPK-α1, but failed to protect the cells from palmitate. Shear stress equally protected the wild type HUVECs and those lacking either α1, or α2, or both AMPK-α isoforms; however, the protective effect of AMPK reappeared after returning to static conditions. Moreover, in human adipose microvascular endothelial cells isolated from obese diabetic individuals, shear stress was a strong protector from palmitate lipotoxicity, thus highlighting the importance of circulation that is often obstructed in obesity/T2D. Altogether, these results indicate that AMPK is important for vascular endothelial cell protection against lipotoxicity in the static environment, however it may be dispensable for persistent and more effective protection exerted by shear stress.

ЦЕЛЬ: сравнить влияние семаглутида 1 мг и лираглутида 3 мг на массу тела, инсулинорезистентность и углеводный обмен у пациентов с длительным анамнезом ожирения и сахарного диабета 2 типа (СД2) в течение 6 месяцев терапии. МАТЕРИАЛЫ И МЕТОДЫ: в исследование включались пациенты с длительным анамнезом ожире- ния (ИМТ>35 кг/м2) и СД2, из них одна группа получала семаглутид в максимальной дозе 1 мг подкожно 1 раз в неделю, вторая группа получала лираглутид в максимальной дозе 3 мг подкожно 1 раз в день. Выраженность инсулинорезистентности была оценена двумя способами – методом гиперинсулинемиче- ского эугликемического клэмп-теста (с вычислением М-индекса) и расчетным методом с использованием гомеостатической модели HOMA-IR (HOmeo-stasis Model Assessment-Insulin Resistance). С целью оценки композиционного состава тела проводилась биоимпедансометрия (InBody 770, Korea). Гликированный гемоглобин (HbA1c) определяли методом высокоэффективной жидкостной хроматографии на анализаторе D10 (BioRad). Статистическая обработка проводилась с помощью программы Statistica 13.3, различия между группами оценивали с помощью критерия Манна−Уитни. РЕЗУЛЬТАТЫ: в каждую группу набрано по 10 пациентов. Пациенты исходно в двух группах были сопо- ставимы по полу, возрасту, ИМТ, окружности талии (ОТ), HBA1c. Нами оценивалась динамика метаболических параметров через 6 месяцев терапии. Семаглутид 1 мг/нед и лираглутид 3,0 мг/сут равноценно снижали выраженность висцерального ожирения, процентное общее содержание жира, улучшали чувствитель- ность к инсулину. Статистически значимые различия в снижении уровня HbA1с также отсутствовали (p=0,52; в группе семаглутида с 7,0% [5,5;9,4] до 5,95% [5,4;7,6]; в группе лираглутида с 8,1% [7,0;10,0] до 6,1% [5,8;7,3]). Однако лираглутид 3,0 мг приводил к более значимому снижению ИМТ (p<0,05; с 42,8 кг/м2 [33,6;58,2] до 34,1 кг/м2 [31,3;51,2] и уменьшению ОТ (p<0,05; с 122 см [109;141] до 112 см [102;129]), в сравнении с груп- пой, находящихся на терапии семаглутидом 1 мг/нед (ИМТ c 43 кг/м2 [37,9;50,7] до 41,4 кг/м2 [36,2;46,2], ОТ с 129,5 см [113;153] до 124 см [108;144]). ВЫВОДЫ: по данным нашего исследования сахароснижающий эффект семаглутида и лираглутида сопо- ставимы, при этом лираглутид в дозе 3,0 мг/сут показал более выраженный эффект в отношении снижения массы тела в сравнении с семаглутидом 1 мг/нед.

Бариатрическая хирургия является одним из самых эффективных способов снижения веса, а также способствует улучшению показателей углеводного обмена у пациентов с ожирением и сахарным диабетом 2 типа (СД 2) типа вплоть до развития ремиссии СД 2. Достижение ремиссии СД 2 после бариатрической операции варьирует от 30 до 98% и зависит от различных факторов. Ряд исследований показал наличие изменений микробиоты кишечника (КМ) после бариатрических операций. Представляется интересным связь между достижением ремиссии СД 2 и изменением состава КМ. ЦЕЛЬ: оценить динамику изменения состава кишечной микробиоты у пациентов после бариатриче- ского вмешательства. МАТЕРИАЛЫ И МЕТОДЫ: в исследование были включены пациенты с морбидным ожирением (индекс массы тела (ИМТ) ≥ 40 кг/м2) и СД 2, которым была выполнена бариатрическая операция в объеме лапаро- скопического минигастрошунтирования. Проводилась оценка динамики массы тела, метаболических по- казателей, гормонов ЖКТ, а также состава микробиоты и метаболома стула исходно и через 6 и 12 месяцев после оперативного вмешательства. РЕЗУЛЬТАТЫ: в исследование включено 28 пациентов. Через 12 месяцев после оперативного лечения наблюдается снижение веса относительно исходного на – 42 кг [-57.4; -35], достижение целевых показа- телей гликированного гемоглобина (HbA1с) c 6.8% [6.3; 7.9] до 5.7% [5.3; 5.9]. Половина пациентов (n=14) достигли полной ремиссии СД после операции с отменой сахароснижающей терапии. Также отмечалось значимое улучшение липидного профиля и уровня мочевой кислоты, снижение инсулинорезистентности (ИР). При оценке гормонов ЖКТ наблюдалось значительное увеличение базального уровня адипонектина после операции; в отношении базальной секреции инкретиновых гормонов (ГПП-1, глюкагон) значимых различий получено не было. Также наблюдалось снижение маркеров хронического системного воспа- ления: уровня эндотоксина и С-реактивного белка (СРБ) в крови у пациентов. Части пациентов (n=17) проведены полногеномное секвенирование и метаболомный анализ КМ. В результате зафиксированы изменения в уровне ряда метаболитов в контрольной точке 6 месяцев после операции, однако, к концу наблюдения состав метаболитов был схож с их дооперационным уровнем. При этом зафиксированное изменение представленности некоторых таксонов бактерий (Fuzobacterium, Escherichia/Shigella, Gemella) сохранялись к концу наблюдения. ВЫВОДЫ: минигастрошунтирование сопровождается значимым улучшением метаболического профиля пациентов с ожирением и СД 2, а также динамикой состава КМ. Требуются дальнейшие исследования для оценки ассоциации между достижением ремиссии СД 2 и профилем КМ. ФИНАНСИРОВАНИЕ: работа выполнена в рамках государственного задания НИОКТР 123021300168-7 «Воздействие на органы чувств (обоняние и вкус) и микробиоценоз ЖКТ с целью регуляции аппетита, веса и гликемии при сахарном диабете 2 типа».

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.