The aim of the project is to study the role of epicardial fat in the onset and development of heart failure focusing on the significance of local inflammation in epicardial fat and the identification of novel regulatory factors contributing to this process. Plasma, urine, epicardial and subcutaneous fat samples will be obtained from patients with heart failure of various severity including those with planned implantation of left ventricular assist device during cardiac surgery. The inflammatory status of adipose tissue will be characterized in depth using transcriptomics, immunohistochemistry and flow cytometry. We will focus on the role of novel antiinflammatory lipid mediators - Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) in development of heart failure and their correlation with clinical characteristics. Metabolomics and lipidomics will be used to identify novel regulatory factors. The project will contribute to clarification of the role of epicardial fat in the development of heart failure and in the longer perspective to possible novel approaches to its treatment.

Cílem projektu je studovat úlohu epikardiálního tuku při vzniku a rozvoji srdečního selhání se zaměřením na význam lokální zánětlivé reakce v epikardiálním tuku a identifikaci nových regulačních faktorů přispívajících k tomuto procesu. Vzorky plazmy, moči, epikardiálního a podkožního tuku budou pacientům se srdečním selháním různé tíže, včetně nemocných podstupujících implantaci mechanické srdeční podpory, odebrány během kardiochirurgické operace. Zánětlivý stav tukové tkáně bude podrobně charakterizován pomoci transkriptomiky, imunohistochemie a průtokové cytometrie. Specificky se zaměříme na úlohu nových protizánětlivých lipidových mediátorů Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) při rozvoji srdečního selhání a jejich korelaci s klinickými charakteristikami. K identifikaci nových regulačních faktorů bude využito metabolomiky a lipidomiky. Projekt přispěje k objasnění úlohy perikardiálního tuku při rozvoji srdečního selhání a v dlouhodobé perspektivě i k možné identifikaci nových léčebných přístupů.

• Klíčová slova
• Heart failure, srdeční selhání, transkriptomika, lipidomika, lipidomics, epikardiální tuk, subklinický zánět, epicardial fat, subclinical inflammation, transriptomics,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

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.

• MeSH
• bariatrická chirurgie * metody   MeSH
• hmotnostní přírůstek účinky léků   MeSH
• hmotnostní úbytek * účinky léků   MeSH
• kombinovaná terapie MeSH
• látky proti obezitě * terapeutické užití   MeSH
• lidé MeSH
• obezita * chirurgie   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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.

• MeSH
• antiflogistika terapeutické užití   farmakologie   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu farmakoterapie   metabolismus   diagnóza   MeSH
• epikardiální adipózní tkáň MeSH
• funkce levé komory srdeční účinky léků   MeSH
• glifloziny * terapeutické užití   farmakologie   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu * metabolismus   MeSH
• metabolomika MeSH
• perikard * metabolismus   účinky léků   MeSH
• srdeční selhání * metabolismus   patofyziologie   farmakoterapie   MeSH
• stupeň závažnosti nemoci * MeSH
• tepový objem účinky léků   MeSH
• tuková tkáň * účinky léků   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• břicho chirurgie   MeSH
• dospělí MeSH
• kontinuální monitorování glukózy MeSH
• krevní glukóza * analýza   MeSH
• kritický stav * MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování fyziologických funkcí metody   MeSH
• senioři MeSH
• studie proveditelnosti MeSH
• transplantace orgánů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Maternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls. METHODS: In this prospective, longitudinal case-control study - including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women - fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors - including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) - were analyzed across three time periods: the last menstrual period to 13 (V1), 14-22 (V2), and 23-32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed. RESULTS: At 28-32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18-22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28-32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester. CONCLUSION: In women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

• MeSH
• diabetes mellitus 1. typu * komplikace   MeSH
• dopplerovská echokardiografie MeSH
• fetální srdce diagnostické zobrazování   MeSH
• gestační diabetes * MeSH
• glykovaný hemoglobin MeSH
• hemodynamika MeSH
• krevní glukóza MeSH
• lidé MeSH
• longitudinální studie MeSH
• prospektivní studie MeSH
• studie případů a kontrol MeSH
• syndrom Nijmegen breakage * MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH