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1.
Artigo em Inglês | MEDLINE | ID: mdl-34586754

RESUMO

OBJECTIVE: The objective of this study is to assess the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19. METHODS: Post-hoc analysis from the nationwide observational CORONADO study: patients with T2D and history of MBS were matched with patients without MBS for age, sex and body mass index (BMI) either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2 398 CORONADO participants, 20 had history of MBS. When matching for BMI at the time of MBS and after adjustment on diabetes duration, the CPO occurred less frequently within 7 days (3 vs 17 events, OR: 0.15 [0.01-0.94], P=0.03) and 28 days (3 vs 19 events, OR: 0.11 (0.01-0.71), P=0.02) in patients with MBS (n=16) vs controls (n=44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID-19 prognosis in patients with diabetes with history of MBS compared to those without MBS.

2.
Front Endocrinol (Lausanne) ; 12: 726967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484128

RESUMO

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.


Assuntos
COVID-19/metabolismo , Cardiomiopatias/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/complicações , COVID-19/imunologia , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inflamação , Gordura Intra-Abdominal/patologia , Obesidade/complicações , Obesidade/imunologia , Obesidade/patologia , Pericárdio , Prognóstico , SARS-CoV-2/metabolismo , Serina Endopeptidases/metabolismo
4.
Diabetes Metab ; 47(5): 101216, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33309936

RESUMO

AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.

5.
Mil Med ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331910

RESUMO

INTRODUCTION: Today, the prevalence of overweight and obesity is, respectively, 49% and 17% among French adults. This research investigates their existence in the French Armed Forces, in terms of the impact on military operative response and military readiness. As no previous studies have evaluated the weight status of the whole French Armed Forces, this work assesses the situation for the first time in France. MATERIAL AND METHODS: A prospective cross-sectional study was carried out between September 2016 and April 2017. A single anonymous questionnaire gathered the sociodemographic variables and usual care medical data. The source population was active duty members serving in units reporting to the South-Eastern French Regional Military Health Department. RESULTS: Among 1,589 respondents, prevalence of overweight and obesity was, respectively, 38.7% and 10%. Mean waist circumference was 78.2 ± 9.1 cm for women and 89.1 ± 10.5 cm for men. A third of female military and one-fifth of male military had a measure bigger than the standard International Diabetes Federation. Age, sex, weekly fitness activity, and rank were significant independent predictors of body weight excess. Less than 5% of the study population reported a diagnosis of comorbidity: diabetes 2%, high blood pressure 1%, and dyslipidemia 1.5%. CONCLUSIONS: As all armies, the French Armed Forces are affected by obesity. Nevertheless, the prevalence of obesity seems lower than in other Western armies. In the French army, as in the general population, obesity is correlated with socioeconomic status and level of education. However, compared to the general French population, there is less obesity and overweight in the French Armed Forces. Moreover, overweight and obese military members have a lower cardiovascular risk than their civilian counterparts. Enlistment standards, military occupational activity, and a mandatory high level of physical fitness could explain these different proportions of overweight and obesity. This raises the question of the protective effect of regular physical activity. Is this a serious way to fight against the growing prevalence of overweight and obesity in Western countries? Indeed, this is a significant public health issue, which also affects the military's quick response force capacity and strategic capabilities. Therefore, the identification of specific demographic characteristics should be considered in developing prevention programs.

6.
J Clin Med ; 9(11)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233575

RESUMO

Diabetes mellitus (DM) has been identified as a risk factor for severe COVID-19. DM is highly prevalent in the general population. Defining strategies to reduce the health care system burden and the late arrival of some patients thus seems crucial. The study aim was to compare phenotypic characteristics between in and outpatients with diabetes and infected by COVID-19, and to build an easy-to-use hospitalization prediction risk score. This was a retrospective observational study. Patients with DM and laboratory- or CT-confirmed COVID-19, who did (n = 185) and did not (n = 159) require hospitalization between 10 March and 10 April 2020, were compared. Data on diabetes duration, treatments, glycemic control, complications, anthropometrics and peripheral oxygen saturation (SpO2) were collected from medical records. Stepwise multivariate logistic regressions and ROC analyses were performed to build the DIAB score, a score using no more than five easy-to-collect clinical parameters predicting the risk of hospitalization. The DIAB score was then validated in two external cohorts (n = 132 and n = 2036). Hospitalized patients were older (68.0 ± 12.6 vs. 55.2 ± 12.6 years, p < 0.001), with more class III obesity (BMI ≥ 40 kg/m2, 9.7 vs. 3.5%, p = 0.03), hypertension (81.6 vs. 44.3%, p < 0.0001), insulin therapy (37% vs. 23.7%, p = 0.009), and lower SpO2 (91.6 vs. 97.3%, p < 0.0001) than outpatients. Type 2 DM (T2D) was found in 94% of all patients, with 10 times more type 1 DM in the outpatient group (11.3 vs. 1.1%, p < 0.0001). A DIAB score > 27 points predicted hospitalization (sensitivity 77.7%, specificity 89.2%, AUC = 0.895), and death within 28 days. Its performance was validated in the two external cohorts. Outpatients with diabetes were found to be younger, with fewer diabetic complications and less severe obesity than inpatients. DIAB score is an easy-to-use score integrating five variables to help clinicians better manage patients with DM and avert the saturation of emergency care units.

7.
Obes Surg ; 30(7): 2791-2799, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32314256

RESUMO

Celiac disease is an immune-mediated enteropathy associated with malabsorptive syndrome and fat-soluble vitamin deficiencies. Celiac disease affects 1% of individuals but is largely underdiagnosed, as its multifaceted clinical presentations create challenging diagnostic scenarios. With the rise of the obesity epidemic, doctors are increasingly seeing celiac disease patients with overweight or obesity, which raises the question of bariatric surgery. However, few studies so far have investigated bariatric surgery in this patient population. Here, we provide a comprehensive review of the literature on celiac disease, its nutritional consequences and complications, and we discuss the possible impact of bariatric surgery on weight loss, nutritional deficiencies, response to gluten-free diet, and long-term post-operative complications. We also review the effect of bariatric surgery on the incidence of celiac disease.


Assuntos
Cirurgia Bariátrica , Doença Celíaca , Derivação Gástrica , Obesidade Mórbida , Cirurgia Bariátrica/efeitos adversos , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Gastrectomia , Humanos , Obesidade/complicações , Obesidade/cirurgia , Obesidade Mórbida/cirurgia
8.
Cells ; 9(2)2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012908

RESUMO

This study details the clinical and cellular phenotypes associated with two missense heterozygous mutations in LMNA, c.1745G > T p.(Arg582Leu), and c.1892G> A p.(Gly631Asp), in two patients with early onset of diabetes mellitus, hypertriglyceridemia and non-alcoholic fatty liver disease. In these two patients, subcutaneous adipose tissue was persistent, at least on the abdomen, and the serum leptin level remained in the normal range. Cellular studies showed elevated nuclear anomalies, an accelerated senescence rate and a decrease of replication capacity in patient cells. In cellular models, the overexpression of mutated prelamin A phenocopied misshapen nuclei, while the partial reduction of lamin A expression in patient cells significantly improved nuclear morphology. Altogether, these results suggest a link between lamin A mutant expression and senescence associated phenotypes. Transcriptome analysis of the whole subcutaneous adipose tissue from the two patients and three controls, paired for age and sex using RNA sequencing, showed the up regulation of genes implicated in immunity and the down regulation of genes involved in development and cell differentiation in patient adipose tissue. Therefore, our results suggest that some mutations in LMNA are associated with severe metabolic phenotypes without subcutaneous lipoatrophy, and are associated with nuclear misshaping.


Assuntos
Lamina Tipo A/genética , Síndrome Metabólica/genética , Mutação/genética , Tecido Adiposo/patologia , Biópsia , Forma do Núcleo Celular , Senescência Celular , Feminino , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo
9.
Arterioscler Thromb Vasc Biol ; 40(4): 986-1000, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102570

RESUMO

OBJECTIVE: Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS: CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.


Assuntos
Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/metabolismo , Pericárdio/metabolismo , Plasmalogênios/metabolismo , Idoso , HDL-Colesterol/sangue , VLDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/metabolismo
10.
J Clin Endocrinol Metab ; 105(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589290

RESUMO

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/patologia , Células Endoteliais/efeitos dos fármacos , Exenatida/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Neovascularização Patológica/patologia , Idoso , Animais , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Feminino , Seguimentos , Humanos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Morfogênese , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Prognóstico , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia
12.
J Assist Reprod Genet ; 35(7): 1317-1324, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29754264

RESUMO

INTRODUCTION: Although bariatric surgery seems to increase spontaneous fertility by improving ovulatory function in young women, its impact on ovarian reserve remains largely unknown. OBJECTIVE: To evaluate changes in serum anti-Mullerian hormone (AMH) levels in reproductive-age severely obese women after bariatric surgery (BS). METHODS: AMH levels were measured retrospectively in 39 women (mean age 34.6 ± 1.1 years, range 18-45) that underwent a sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) at baseline, and 6 and 12 months after BS. Metabolic and micronutrient status, including fasting plasma insulin and glucose, HOMA-IR, leptin, adiponectin, calcium, albumin, transthyretin, ferritin, vitamins (B9, B12, B1, A, E, D), zinc, and selenium, were assessed in all patients before and 1 year after BS. RESULTS: Of the patients, 79% had class-3 obesity. At 6 and 12 months, mean total weight losses (TWL) were 26 and 30%; mean excess weight losses (EWL) were 61.7 and 70.2%. Compared to baseline, AMH levels significantly decreased by 18% at 6 months, and 32% at 12 months post-operatively (p = 0.010 and p = 0.001, respectively). There was no correlation between AMH variation and changes in metabolic parameters or micronutrient levels. Remarkably, changes in AMH levels did not differ between sleeve and RYGB patients and were not correlated with EWL. CONCLUSION: This pilot study shows a drastic reduction in AMH levels at 1 year after BS in reproductive-age severely obese women, which was not related to weight loss: this suggests a negative impact of BS on ovarian reserve, at least in the short term.


Assuntos
Hormônio Antimülleriano/sangue , Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Reserva Ovariana/genética , Adolescente , Adulto , Índice de Massa Corporal , Pré-Escolar , Feminino , Gastrectomia , Derivação Gástrica , Humanos , Lactente , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/fisiopatologia , Reserva Ovariana/fisiologia , Perda de Peso , Adulto Jovem
13.
Pharmacol Res ; 131: 211-217, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29452290

RESUMO

Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m2 (IQR, 40.6-48.7 kg/m2)] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r = -0.56, p < .0001). Receiver operating characteristic curves indicated that among BSD, LBW (cut-off >55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (ß = -0.47 ±â€¯0.08, p < .0001 and ß = -0.19 ±â€¯0.08; p = .02, respectively). In BS morbidly obese patients receiving LMWH for thromboprophylaxis after BS, LBW and eGFR are the main determinants of anti-Xa level, and could be proposed in LMWH-based thromboprophylaxis dosing algorithms. The efficacy of a LBW-scale based dosing algorithm for optimal VTE prevention deserves further prospective randomized trials.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Adulto , Cirurgia Bariátrica , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Peso Corporal Ideal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Perda de Peso
14.
Gastrointest Endosc ; 87(2): 429-437, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28750839

RESUMO

BACKGROUND AND AIMS: Fistulas after sleeve gastrectomy are major adverse events of bariatric surgery. The endoscopic management strategy evolved from closure to internal drainage after 2013. The main objective of our study was to evaluate and compare these different approaches. METHODS: This retrospective study included all patients treated for fistulas after sleeve gastrectomy in a referral center. Closure management was defined as initial treatment that used a covered metal stent and/or endoclips. Internal drainage management was defined as initial treatment by nasocystic drain and/or a double-pigtail stent. RESULTS: A total of 100 patients (women N = 78, mean [± standard deviation {SD}] age 42 ± 12 years) were included between 2007 and 2015. The mean (± SD) delay between sleeve gastrectomy and the first endoscopy was 82 ± 125 days. The overall success of endoscopic treatment was 86% within 6 ± 27 months. Two patients died. The primary success of internal drainage and closure management occurred in 19 of 22 (86%) and 49 of 77 (63%) patients, respectively. Among patients in failure for closure management, 22 had secondary internal drainage (18 being successful). Success of initial management was significantly higher for internal drainage (P = .043). Factors associated with failure of closure management were in multivariable analysis: collection >5 cm (P = .013). Factors associated with a time >6 months for achieving leakage closure were in multivariable analysis: reoperation before endoscopy (P = .044) and purulent flow at endoscopy (P = .043). CONCLUSIONS: Endoscopic management of fistulas after sleeve gastrectomy was successful in 86% of cases. In cases of collections >5 cm, internal drainage should be proposed first. Surgical reintervention before endoscopy delays treatment success.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Drenagem , Gastrectomia/efeitos adversos , Fístula Gástrica/cirurgia , Complicações Pós-Operatórias/cirurgia , Adulto , Endoscopia Gastrointestinal/instrumentação , Feminino , Gastrectomia/métodos , Fístula Gástrica/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Stents , Instrumentos Cirúrgicos , Fatores de Tempo , Falha de Tratamento
15.
Compr Physiol ; 7(3): 1051-1082, 2017 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-28640452

RESUMO

Epicardial adipose tissue (EAT) is a small but very biologically active ectopic fat depot that surrounds the heart. Given its rapid metabolism, thermogenic capacity, unique transcriptome, secretory profile, and simply measurability, epicardial fat has drawn increasing attention among researchers attempting to elucidate its putative role in health and cardiovascular diseases. The cellular crosstalk between epicardial adipocytes and cells of the vascular wall or myocytes is high and suggests a local role for this tissue. The balance between protective and proinflammatory/profibrotic cytokines, chemokines, and adipokines released by EAT seem to be a key element in atherogenesis and could represent a future therapeutic target. EAT amount has been found to predict clinical coronary outcomes. EAT can also modulate cardiac structure and function. Its amount has been associated with atrial fibrillation, coronary artery disease, and sleep apnea syndrome. Conversely, a beiging fat profile of EAT has been identified. In this review, we describe the current state of knowledge regarding the anatomy, physiology and pathophysiological role of EAT, and the factors more globally leading to ectopic fat development. We will also highlight the most recent findings on the origin of this ectopic tissue, and its association with cardiac diseases. © 2017 American Physiological Society. Compr Physiol 7:1051-1082, 2017.


Assuntos
Tecido Adiposo/metabolismo , Doenças Cardiovasculares/etiologia , Metabolismo dos Lipídeos , Obesidade/etiologia , Pericárdio/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo/diagnóstico por imagem , Animais , Humanos , Pericárdio/citologia , Pericárdio/diagnóstico por imagem
17.
Surg Obes Relat Dis ; 13(2): 320-326, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27720420

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in obese patients undergoing bariatric surgery (BS), but there is neither consensus nor high-level guidelines yet on VTE prophylaxis in this specific population. OBJECTIVE: We aimed to evaluate patterns of BS perioperative thromboprophylaxis practices. SETTING: French obesity specialized care centers (CSO), which are tertiary care referral hospitals for the most severe cases of obesity METHODS: A detailed questionnaire survey (11 opened, 15 closed questions) investigating their prophylactic schemes of anticoagulation (molecule, dose, weight-adjustment, duration, associated measures, follow-up) was sent to the 37 CSO. RESULTS: Completion rate was 92%. Over 90% of respondents indicated using low molecular weight heparin. Enoxaparin was the most commonly used molecule (89%), twice daily (71%), started mostly 6 hours after BS (74%), whereas fondaparinux (9%), dalteparin (6%), and tinzaparin (6%) were less often prescribed. Dosing varied significantly according to centers from 4000 to 12,000 IU/d, with the most commonly used dose being 8000 IU once daily, 83%, as well as treatment duration (1 week, 9%; 3 weeks, 47%). Half CSO adjusted low molecular weight heparin dose to weight. Biological monitoring was performed in 88%. Only 1 center followed systematically anti-Xa activity. Associated measures such as elastic stoking or intermittent pneumatic compression were used in 32% and 26%, respectively, and both were used in 39%. CONCLUSION: This study finds significant discrepancies in thromboprophylaxis practices in obese patients undergoing BS, particularly with respect to treatment duration and dose adjustment, highlighting the urgent need for improved implementation of existing clinical practice guidelines in this VTE high-risk population.


Assuntos
Cirurgia Bariátrica/métodos , Obesidade Mórbida/cirurgia , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/administração & dosagem , Estudos Transversais , Esquema de Medicação , Feminino , França , Humanos , Dispositivos de Compressão Pneumática Intermitente/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/etiologia , Padrões de Prática Médica/estatística & dados numéricos , Autorrelato , Meias de Compressão/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Trombose Venosa/etiologia
18.
J Am Coll Cardiol ; 68(23): 2594-2595, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27931623
20.
Cells ; 5(2)2016 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-27120622

RESUMO

ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient.

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