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A global obesity pandemic is one of the most significant health threats worldwide owing to its close association with numerous comorbidities such as type 2 diabetes mellitus, arterial hypertension, dyslipidemia, heart failure, cancer and many others. Obesity and its comorbidities lead to a higher rate of cardiovascular complications, heart failure and increased cardiovascular and overall mortality. Bariatric surgery is at present the most potent therapy for obesity, inducing a significant weight loss in the majority of patients. In the long-term, a substantial proportion of patients after bariatric surgery experience a gradual weight regain that may, in some, reach up to a presurgical body weight. As a result, anti-obesity pharmacotherapy may be needed in some patients after bariatric surgery to prevent the weight regain or to further potentiate weight loss. This article provides an overview of the use of anti-obesity medications as an augmentation to bariatric surgery for obesity. Despite relatively limited published data, it can be concluded that anti-obesity medication can serve as an effective adjunct therapy to bariatric surgery to help boost post-bariatric weight loss or prevent weight regain.
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Fármacos Antiobesidade , Cirurgia Bariátrica , Obesidade , Redução de Peso , Humanos , Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Redução de Peso/efeitos dos fármacos , Terapia Combinada , Aumento de Peso/efeitos dos fármacosRESUMO
The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in ß-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum.
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BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure. METHODS: 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed. RESULTS: SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects. CONCLUSIONS: Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.
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Tecido Adiposo , Insuficiência Cardíaca , Mediadores da Inflamação , Pericárdio , Índice de Gravidade de Doença , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Feminino , Pericárdio/metabolismo , Pericárdio/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Resultado do Tratamento , Mediadores da Inflamação/metabolismo , Volume Sistólico/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Metabolômica , Biomarcadores/sangue , Tecido Adiposo EpicárdicoAssuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Insulina Glargina , Peptídeos , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/uso terapêutico , Insulina Glargina/administração & dosagem , Hipoglicemiantes/uso terapêutico , Peptídeos/uso terapêutico , Peptídeos/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Resultado do Tratamento , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Combinação de Medicamentos , Receptor do Peptídeo Semelhante ao Glucagon 2RESUMO
OBJECTIVE: Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery. RESEARCH DESIGN AND METHODS: We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL). RESULTS: We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (<1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%. CONCLUSIONS: Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.
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Glicemia , Estado Terminal , Humanos , Masculino , Glicemia/análise , Pessoa de Meia-Idade , Feminino , Idoso , Abdome/cirurgia , Transplante de Órgãos , Estudos de Viabilidade , Adulto , Monitorização Fisiológica/métodos , Monitoramento Contínuo da GlicoseRESUMO
Inflammation is considered a fundamental process accompanying physiological human birth, also playing a role in perinatal pathologies. The goal of the study was to assess the concentrations of inflammatory molecules with respect to the mode of delivery and dynamics of inflammatory molecules in neonatal samples in the first 48-72 hours of life. The concentrations of inflammatory cytokines were measured using the Luminex®xMAP multi-analyte profiling platform in cord blood and peripheral neonatal blood. Study groups included newborns delivered spontaneously (spontaneous group) and via elective caesarean section (elective group). Cord blood concentrations of interleukin 6 (IL-6) and procalcitonin were significantly higher (P < 0.0001) in the spontaneous group compared to the elective group. Neonatal blood concentrations of tumour necrosis factor (TNF) from the elective group were significantly higher com-pared to the spontaneous group (P = 0.0077). The concentrations of procalcitonin and TNF significantly increased within the first 48 to 72 hours following either mode of delivery. IL-6 and IL-18 were significantly higher in neonatal compared to umbilical cord blood in the elective group only, while the increase in the spontaneous group did not reach statistical significance. The concentrations of IL-1α, IL-1ß, IL-17A and IL-22 did not show significant differen-ces between the spontaneous and elective groups as well as between umbilical cord and neonatal blood. Our findings show physiological differences in the levels of inflammatory molecules following spontaneous vaginal delivery and elective caesarean section. The results can be used as baseline values for the research of various pathologies in newborns.
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Cesárea , Interleucina-6 , Gravidez , Recém-Nascido , Humanos , Feminino , Pró-Calcitonina , Parto Obstétrico/métodos , Fator de Necrose Tumoral alfa , Sangue FetalRESUMO
Myokines represent important regulators of muscle metabolism. Our study aimed to explore the effects of a cyclical ketogenic reduction diet (CKD) vs. a nutritionally balanced reduction diet (RD) combined with regular resistance/aerobic training in healthy young males on serum concentrations of myokines and their potential role in changes in physical fitness. Twenty-five subjects undergoing regular resistance/aerobic training were randomized to the CKD (n = 13) or RD (n = 12) groups. Anthropometric and spiroergometric parameters, muscle strength, biochemical parameters, and serum concentrations of myokines and cytokines were assessed at baseline and after 8 weeks of intervention. Both diets reduced body weight, body fat, and BMI. Muscle strength and endurance performance were improved only by RD. Increased musclin (32.9 pg/mL vs. 74.5 pg/mL, p = 0.028) and decreased osteonectin levels (562 pg/mL vs. 511 pg/mL, p = 0.023) were observed in RD but not in the CKD group. In contrast, decreased levels of FGF21 (181 pg/mL vs. 86.4 pg/mL, p = 0.003) were found in the CKD group only. Other tested myokines and cytokines were not significantly affected by the intervention. Our data suggest that changes in systemic osteonectin and musclin levels could contribute to improved muscle strength and endurance performance and partially explain the differential effects of CKD and RD on physical fitness.
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Dieta Cetogênica , Insuficiência Renal Crônica , Treinamento Resistido , Masculino , Humanos , Osteonectina , Força Muscular/fisiologia , Dieta Redutora , Citocinas , Composição Corporal/fisiologiaAssuntos
Cirurgia Bariátrica , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Doenças Cardiovasculares/cirurgia , Obesidade/complicações , Obesidade/cirurgia , Duodeno/cirurgia , Fatores de Risco , Cirurgia Bariátrica/efeitos adversos , Resultado do Tratamento , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Derivação Gástrica/efeitos adversosRESUMO
Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.
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MicroRNAs , Sepse Neonatal , Sepse , Humanos , Recém-Nascido , Lactente , MicroRNAs/genética , Sepse Neonatal/diagnóstico , Interleucina-18 , Fator A de Crescimento do Endotélio Vascular , Biomarcadores/metabolismo , Sepse/diagnóstico , Sepse/genética , InflamaçãoRESUMO
(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.
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Procedimentos Cirúrgicos Cardíacos , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirurgia , Humanos , Interleucina-6/metabolismo , Pericárdio/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. The reliable models that might predict weight reducing potential at the individual level have not been identified yet. However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity. We aimed to review the efficacy of GLP-1 RAs approved for weight management in individuals with and without diabetes and discuss some potential mechanisms for consistently observed differences in efficacy between these two populations. The mean weight loss difference between GLP-1 RAs and placebo as add-on to lifestyle intervention in patients with diabetes was 4% to 6.2% compared to 6.1 to 17.4% in people without diabetes. Semaglutide compared to liraglutide resulted in greater weight loss. Some hypothetical explanations for the weaker anti-obesity response for both GLP-1 RAs in people with diabetes include the background medications that promote weight gain, the fear of hypoglycaemia inherently related to the treatment of diabetes, a decrease in glycosuria and subsequently less weight loss in diabetics, an altered microbiota in patients with obesity and diabetes and a genetic background that predispose to weight gain in patients with diabetes. Moreover, people with diabetes may have had obesity for longer and may be less adherent to exercise, which seems to potentiate the effects of GLP-1 RA. Emerging multimodal approaches combining peptides targeting receptors at different levels might therefore be of additional benefit particularly in patients with diabetes.
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Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Aumento de Peso , Redução de PesoRESUMO
AIMS: To evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes. MATERIALS AND METHODS: Change from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme. Treatment differences were analysed using a mixed model for repeated measurements for continuous variables and a logistic regression model for the binary endpoint. Pooled safety data were analysed descriptively. RESULTS: Changes from baseline in HbA1c and body weight, and the odds of achieving HbA1c <7.0%, were greater with oral semaglutide 14 mg/flex (n = 1934) and higher or similar with oral semaglutide 7 mg (n = 823) versus comparators (n = 2077) across most subgroups. Changes in HbA1c with oral semaglutide 14 mg/flex were greater for patients with higher baseline HbA1c (HbA1c >9.0%: -1.7% to -2.6%; HbA1c <8.0%: -0.7% to -1.2%). In some trials, Asian patients experienced greater HbA1c reductions with oral semaglutide 14 mg/flex (-1.5% to -1.8%) than other racial groups (-0.6% to -1.6%). The overall incidence of adverse events (AEs) with oral semaglutide was similar to that with comparators and was consistent across subgroups. More gastrointestinal AEs were observed with oral semaglutide, versus comparators, across subgroups. CONCLUSIONS: Oral semaglutide demonstrated consistently greater HbA1c and body weight reductions across a range of patient characteristics, with greater HbA1c reductions seen at higher baseline HbA1c levels.
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Diabetes Mellitus Tipo 2 , Peso Corporal , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversosRESUMO
Type 2 diabetes mellitus represents a major health problem with increasing prevalence worldwide. Limited efficacy of current therapies has prompted a search for novel therapeutic options. Here we show that treatment of pre-diabetic mice with mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, improves glucose tolerance and reduces body weight with most pronounced reduction of visceral adipose tissue due to reduced food intake, suppressed adipogenesis and elimination of senescent cells. Glucose-lowering effect of mitochondrially targeted tamoxifen is linked to improvement of type 2 diabetes mellitus-related hormones profile and is accompanied by reduced lipid accumulation in liver. Lower senescent cell burden in various tissues, as well as its inhibitory effect on pre-adipocyte differentiation, results in lower level of circulating inflammatory mediators that typically enhance metabolic dysfunction. Targeting senescence with mitochodrially targeted tamoxifen thus represents an approach to the treatment of type 2 diabetes mellitus and its related comorbidities, promising a complex impact on senescence-related pathologies in aging population of patients with type 2 diabetes mellitus with potential translation into the clinic.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Idoso , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Humanos , Camundongos , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêuticoRESUMO
Background: Brown adipose tissue (BAT) is a therapeutic target to combat obesity and related disorders. Pheochromocytoma and functional paraganglioma (PPGL) are associated with activated BAT due to catecholamine excess. Our aim was to evaluate BAT activity by gene profile and assess its relation to clinical characteristics and overproduced catecholamine. Methods: mRNA expression of 15 genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was measured via RT-PCR in 25 patients with PPGL and 14 controls undergoing cholecystectomy. Results: We found in VAT of PPGL higher expression of UCP1 (p < 0.001), CEBPB, PPARGC1A (both p < 0.001), PRDM16 (p = 0.069) and DIO2 (p = 0.005). UCP1 expression correlated only with norepinephrine levels and its metabolite. UCP1 expression, among others, correlated negatively with BMI, age and positively with HDLc levels. Dominance of BAT or BeAT markers was not assessed in PPGL. In SAT of PPGL, we found higher expression of ADRB3, CIDEA (both p < 0.05), and PPARGC1A (p = 0.001), but not UCP1. Conclusion: We demonstrate signs of UCP1-dependent norepinephrine-induced thermogenesis connected with higher expression of DIO2, PPARGC1A, CEBPB and PRDM16 in retroperitoneal VAT of PPGL and its relations to circulating HDLc and triglycerides levels. However, no direct relationship with increased basal energy metabolism measured by calorimetry was found.
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Obesity is a significant problem worldwide. Several serious diseases that decrease patient quality of life and increase mortality (high blood pressure, dyslipidaemia, type 2 diabetes etc.) are associated with obesity. Obesity treatment is a multidisciplinary and complex process that requires maximum patient compliance. Change of lifestyle is fundamental in the treatment of obesity. While pharmacotherapeutic options are available, their efficacy is limited. Surgical treatment though highly effective, carries the risk of complications and is thus indicated mostly in advanced stages of obesity. Endoscopic treatments of obesity are less invasive than surgical options, and are associated with fewer complications and nutritional deficits. Currently, there is a large spectrum of endoscopic methods based on the principles of gastric volume reduction, size restriction and gastric or small bowel bypass being explored with only few available in routine practice. The aim of this publication is to present an up-to-date summary of available endoscopic methods for the treatment of obesity focusing on their efficacy, safety and nutritional aspects.
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Cirurgia Bariátrica/métodos , Endoscopia do Sistema Digestório/métodos , Estado Nutricional , Obesidade/cirurgia , Humanos , Obesidade/fisiopatologia , Resultado do TratamentoRESUMO
(1) Background: empagliflozin, sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an effective antidiabetic agent with strong cardio- and nephroprotective properties. The mechanisms behind its cardio- and nephroprotection are still not fully clarified. (2) Methods: we used male hereditary hypertriglyceridemic (hHTG) rats, a non-obese model of dyslipidaemia, insulin resistance, and endothelial dysfunction fed standard diet with or without empagliflozin for six weeks to explore the molecular mechanisms of empagliflozin effects. Nuclear magnetic resonance (NMR)-based metabolomics; quantitative PCR of relevant genes involved in lipid and glucose metabolism, or senescence; glucose and palmitic acid oxidation in isolated tissues and cell lines of adipocytes and hepatocytes were used. (3) Results: empagliflozin inhibited weight gain and decreased adipose tissue weight, fasting blood glucose, and triglycerides and increased HDL-cholesterol. It also improved insulin sensitivity in white fat. NMR spectroscopy identified higher plasma concentrations of ketone bodies, ketogenic amino acid leucine and decreased levels of pyruvate and alanine. In the liver, adipose tissue and kidney, empagliflozin up-regulated expression of genes involved in gluconeogenesis and down-regulated expression of genes involved in lipogenesis along with reduction of markers of inflammation, oxidative stress and cell senescence. (4) Conclusion: multiple positive effects of empagliflozin, including reduced cell senescence and oxidative stress, could contribute to its long-term cardio- and nephroprotective actions.
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Tecido Adiposo/metabolismo , Compostos Benzidrílicos/administração & dosagem , Senescência Celular/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Glucosídeos/administração & dosagem , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/metabolismo , Hipoglicemiantes/administração & dosagem , Rim/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Células 3T3-L1 , Administração Oral , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Dislipidemias/tratamento farmacológico , Gluconeogênese/genética , Células Hep G2 , Humanos , Resistência à Insulina , Lipogênese/genética , Masculino , Camundongos , Ratos , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
Immune cells are an inseparable component of adipose tissue intimately involved in most of its functions. Physiologically, they regulate adipose tissue homeostasis, while in case of adipose tissue stress, immune cells are able to change their phenotype, enhance their count and subsequently contribute to the development and maintenance of local adipose tissue inflammation. Immune cells are an important source of inflammatory cytokines and other pro-inflammatory products that further influence not only surrounding tissues but via systemic circulation also the whole organism being thus one of the main factors responsible for the transition from simple obesity to associated metabolic and cardiovascular complications. The purpose of this review is to summarize current knowledge on different adipose tissue immune cell subsets and their role in the development of obesity, type 2 diabetes mellitus and cardiovascular diseases.
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Tecido Adiposo/imunologia , Doenças Cardiovasculares/imunologia , Diabetes Mellitus Tipo 2/imunologia , Sistema Imunitário/fisiologia , Obesidade/imunologia , Tecido Adiposo/metabolismo , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Sistema Imunitário/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/patologia , Macrófagos/fisiologia , Obesidade/metabolismo , Fatores de RiscoRESUMO
The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.
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Doença da Artéria Coronariana/genética , Estresse do Retículo Endoplasmático/genética , Transcriptoma/genética , Tecido Adiposo/metabolismo , Idoso , Doença da Artéria Coronariana/fisiopatologia , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Pericárdio/metabolismo , RNA Mensageiro/genética , Gordura Subcutânea/metabolismoRESUMO
INTRODUCTION: Obesity and atrial fibrillation (AF) pose a significant burden on healthcare systems worldwide. Reduction of body weight has been documented to reduce the risk of AF. Little is known about the effect of different weight-reducing interventions including bariatric surgery in obese individuals on the risk of arrhythmia recurrence following catheter ablation (CA) for AF, and about the pathophysiological mechanisms linking these two conditions. METHODS: The Effect of complex weigHt-reducing interventiOns on rhythm control in oBese subjects wITh Atrial Fibrillation (HOBIT-AF) is a single-blinded, parallel-group randomised controlled trial with 18-month follow-up to assess the effect of complex weight-reducing interventions supported by the use of smart technologies and bariatric surgery on the arrhythmia burden in obese individuals following CA for AF. One hundred and sixty individuals (age 18-70 years, body mass index ≥ 30 kg/m2) will be randomised in a 1:1 fashion to undergo a structured weight reduction programme and sleeve gastrectomy (when indicated and preferred by the patient) aiming to achieve greater than 10% weight reduction from baseline (intervention group) or standard post-ablation medical care (control group). Two-week continuous ECG monitoring will be used 3 and 18 months after CA to assess the arrhythmia burden. Other investigations will include transthoracic echocardiography with quantification of epicardial adipose tissue, and markers of low-grade inflammation and circulating adipokines. PLANNED OUTCOMES: The main objective is to assess the effect of complex weight-reducing interventions on the arrhythmia burden and quality of life. Subgroup analyses to identify patient subgroups preferentially benefiting from weight loss related to a decrease in arrhythmia burden will be performed. Exploratory objectives will include investigation of potential mechanisms linking weight reduction with amelioration of arrhythmia burden such as changes in markers of low-grade inflammation, circulating adipokines, cytokines, monocytes or reduction of epicardial adipose tissue volume. TRIAL REGISTRATION: NCT04560387.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Adolescente , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do Tratamento , Redução de Peso , Adulto JovemRESUMO
Overweight and obesity prevalence in middle aged subjects in the Czech Republic is more than 50 per cent, obesity is found in around 26 per cent of population. Obesity management is a long-term and time-consuming process. Early start of the treatment can prevent continuous weight gain and development of co-morbidities. General practitioners see obese patients usually as the first and they represent the first point of contact for adults with obesity. The basis of obesity management is a change of the lifestyle with added pharmacotherapy and/or bariatric/metabolic surgery. The paper presents overview of methods in obesity diagnostics and management and possibilities of their use in GPs daily practice.