RESUMO
ABBREVIATIONS: PSMF = protein-sparing modified fast; VLCMP = very-low-calorie meal plans.
Assuntos
Ingestão de Energia , Obesidade , Bariatria , EndocrinologiaRESUMO
ABBREVIATIONS: CKD = chronic kidney disease DM = diabetes mellitus eGFR = estimated glomerular filtration rate FDA = Food & Drug Administration.
Assuntos
Taxa de Filtração Glomerular , Metformina/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Endocrinologia , Humanos , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
OBJECTIVE: Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups. METHODS: We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m2 with at least 1 comorbidity, or a minimum BMI of 30 kg/m2, at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data. RESULTS: Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo. CONCLUSION: Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals. ABBREVIATIONS: A1c = glycated hemoglobin BMI = body mass index CI = confidence interval FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 hsCRP = high-sensitivity C-reactive protein SCALE = Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes T2DM = type 2 diabetes mellitus.
Assuntos
Hispânico ou Latino , Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Sobrepeso/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Adulto , Comorbidade , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Liraglutida/administração & dosagem , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/etnologia , Sobrepeso/etnologia , Fatores de RiscoRESUMO
BACKGROUND: Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. METHODS: We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. RESULTS: There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. CONCLUSIONS: Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. CLINICAL TRIALS REGISTRATION: This study is registered on http://www.clinicaltrials.gov/: NCT00546728.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Microcirculação/efeitos dos fármacos , Obesidade Abdominal/complicações , Peptídeos/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Extremidade Superior/irrigação sanguínea , Peçonhas/uso terapêutico , Idoso , Análise de Variância , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Exenatida , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperemia/fisiopatologia , Mediadores da Inflamação/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/fisiopatologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. The American Society for Parenteral & Enteral Nutrition fully endorses sections of these guidelines that address the metabolic and nutritional management of the bariatric surgical patient.
Assuntos
Cirurgia Bariátrica , Terapia Nutricional/normas , Assistência Perioperatória/normas , Cuidados Pós-Operatórios/normas , Cirurgia Bariátrica/efeitos adversos , Comorbidade , Derivação Gástrica , Humanos , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/metabolismo , Síndromes de Malabsorção/fisiopatologia , Avaliação Nutricional , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Síndromes da Apneia do Sono/epidemiologiaAssuntos
Assistência Odontológica para Doentes Crônicos , Diabetes Mellitus/terapia , Glicemia/análise , Candidíase Bucal/complicações , Assistência Odontológica Integral , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/sangue , Diabetes Mellitus/prevenção & controle , Humanos , Educação de Pacientes como Assunto , Doenças Periodontais/complicações , Doenças Periodontais/prevenção & controleRESUMO
BACKGROUND: Data suggest that carvedilol possesses antioxidant properties that might provide vascular protection. We sought to compare the effects of carvedilol and metoprolol tartrate on endothelial function and oxidative stress in a head-to-head trial. METHODS: Thirty-four patients with type 2 diabetes mellitus (T2DM) and hypertension were randomized to receive either carvedilol (n = 16) or metoprolol (n = 18) in addition to their current antihypertensive medications for 5 months. The following variables were measured pre- and posttreatment: blood pressure, fasting glucose and insulin, insulin resistance by homeostasis-model assessment, hemoglobin A1c, lipids, C-reactive protein (CRP), 8-isoprostane, asymmetric dimethylarginine, oxidized LDL cholesterol, ultrasound assessment of brachial-artery flow-mediated dilation (FMD), nitroglycerin-induced endothelium-independent dilation (EID), brachial and carotid artery distension, distensibility and compliance, and carotid artery intima-media thickness (cIMT). RESULTS: Both carvedilol and metoprolol treatment resulted in significant and similar decreases in systolic (P < .05) and diastolic (P < .0001) blood pressure. Compared with metoprolol, carvedilol significantly improved FMD (P < .001). No differences between groups were noted for any of the glycemic or lipid variables except for HDL cholesterol, which significantly decreased (P < .05) in the metoprolol group compared with the carvedilol group. No differences were observed between groups for CRP, the markers of oxidative stress, EID, arterial stiffness, or cIMT. CONCLUSIONS: Compared with metoprolol, carvedilol significantly improves endothelial function in patients with T2DM. Changes in glycemic control and oxidative stress do not seem to explain the observed improvements in FMD, which suggests that other mechanisms may be involved.
Assuntos
Anti-Hipertensivos/uso terapêutico , Carbazóis/uso terapêutico , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Metoprolol/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Propanolaminas/uso terapêutico , Idoso , Carvedilol , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Endotélio Vascular/fisiologia , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
Obesity, is a chronic, biological, preventable, and treatable disease. The accumulation of fat mass causes physical changes (adiposity), metabolic and hormonal changes due to adipose tissue dysfunction (adiposopathy), and psychological changes. Bariatric endocrinology was conceived from the need to address the neuro-endocrinological derangements that are associated with adiposopathy, and from the need to broaden the scope of the management of its complications. In addition to the well-established metabolic complications of overweight and obesity, adiposopathy leads to hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, dysregulation of gut peptides including GLP-1 and ghrelin, the development of an inflammatory milieu, and the strong risk of vascular disease. Therapy for adiposopathy hinges on effectively lowering the ratio of orexigenic to anorexigenic signals reaching the the hypothalamus and other relevant brain regions, favoring a lower caloric intake. Adiposopathy, overweight and obesity should be treated indefinitely with the specific aims to reduce fat mass for the adiposity complications, and to normalize adipose tissue function for the adiposopathic complications. This paper defines the principles of medical practice in bariatric endocrinology-the treatment of overweight and obesity as means to treat adiposopathy and its accompanying metabolic and hormonal derangements.
RESUMO
The term "fat" may refer to lipids as well as the cells and tissue that store lipid (ie, adipocytes and adipose tissue). "Lipid" is derived from "lipos," which refers to animal fat or vegetable oil. Adiposity refers to body fat and is derived from "adipo," referring to fat. Adipocytes and adipose tissue store the greatest amount of body lipids, including triglycerides and free cholesterol. Adipocytes and adipose tissue are active from an endocrine and immune standpoint. Adipocyte hypertrophy and excessive adipose tissue accumulation can promote pathogenic adipocyte and adipose tissue effects (adiposopathy), resulting in abnormal levels of circulating lipids, with dyslipidemia being a major atherosclerotic coronary heart disease risk factor. It is therefore incumbent upon lipidologists to be among the most knowledgeable in the understanding of the relationship between excessive body fat and dyslipidemia. On September 16, 2012, the National Lipid Association held a Consensus Conference with the goal of better defining the effect of adiposity on lipoproteins, how the pathos of excessive body fat (adiposopathy) contributes to dyslipidemia, and how therapies such as appropriate nutrition, increased physical activity, weight-management drugs, and bariatric surgery might be expected to impact dyslipidemia. It is hoped that the information derived from these proceedings will promote a greater appreciation among clinicians of the impact of excess adiposity and its treatment on dyslipidemia and prompt more research on the effects of interventions for improving dyslipidemia and reducing cardiovascular disease risk in overweight and obese patients.
Assuntos
Adiposidade/fisiologia , Dislipidemias/fisiopatologia , Obesidade/fisiopatologia , Adiposidade/efeitos dos fármacos , Conferências de Consenso como Assunto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Humanos , Resistência à Insulina/fisiologia , Obesidade/sangue , Obesidade/tratamento farmacológico , Triglicerídeos/sangueRESUMO
The authors hypothesized that carvedilol controlled-release plus lisinopril combination therapy (C+L) would increase endothelial function and decrease oxidative stress to a greater extent than hydrochlorothiazide plus lisinopril combination therapy (H+L) in obese patients with hypertension. Twenty-five abdominally obese patients (aged 54.4±7.3 years; 14 women) with hypertension/prehypertension were enrolled in a 7-month (two 3-month treatment periods separated by a 1-month washout), randomized, double-blind, controlled, crossover clinical trial comparing C+L vs H+L. Endothelial function, measured by digital reactive hyperemic index (RHI), circulating oxidized low-density lipoprotein (oxLDL), 8-isoprostane, and asymmetric dimethylarginine (ADMA) were obtained at baseline, post-period 1, post-washout, and post-period 2. Analyses were adjusted for baseline measurements by analysis of covariance, with robust variance estimation for confidence intervals and P values. C+L treatment compared to H+L treatment significantly improved RHI (0.74, 95% confidence interval, 0.31-1.19, P =.001). This difference persisted after adjustment for the change in systolic blood pressure. No significant treatment differences were observed for oxLDL, 8-isoprostane, or ADMA. These data provide evidence that independent of blood pressure-lowering, C+L therapy improves endothelial function to a greater extent than H+L therapy. Levels of oxidative stress were not significantly different between treatments, suggesting that other mechanisms may be responsible for the improvement in endothelial function.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Carbazóis/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Lisinopril/administração & dosagem , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Propanolaminas/administração & dosagem , Carvedilol , Estudos Cross-Over , Preparações de Ação Retardada , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologiaRESUMO
Collaborations between physicians, particularly those in academic medicine, and industries that develop pharmaceutical products, medical devices, and diagnostic tests have led to substantial advances in patient care. At the same time, there is a strong awareness that these relationships, however beneficial they may be, should conform to established principles of ethical professional practice. Through a writing committee drawn from diverse disciplines across several institutions, the Association of Clinical Researchers and Educators (ACRE) has written a code of conduct to provide guidance to physicians in observing these principles. Our recommendations are not intended to be prescriptive or inflexible, but rather to be of assistance to physicians in making their own personal decisions on whether, or how, to be involved in research, education, or other collaborations with industry.
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Ética Profissional , Setor de Assistência à Saúde/ética , Relações Interprofissionais/ética , Médicos/ética , Códigos de Ética , Educação Médica Continuada/ética , Humanos , Editoração/ética , Pesquisadores/éticaAssuntos
Emigração e Imigração , Hispânico ou Latino , Obesidade/epidemiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Minnesota , Obesidade/genética , Fatores de Risco , Meio Social , Estados UnidosAssuntos
Liderança , Competição em Planos de Saúde/legislação & jurisprudência , Papel do Médico , Qualidade da Assistência à Saúde/legislação & jurisprudência , Sociedades Médicas , Redução de Custos/legislação & jurisprudência , Humanos , Competição em Planos de Saúde/economia , Minnesota , Qualidade da Assistência à Saúde/economiaAssuntos
Acessibilidade aos Serviços de Saúde/economia , Serviços Preventivos de Saúde/economia , Planos Governamentais de Saúde/economia , Controle de Custos/legislação & jurisprudência , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência , Humanos , Minnesota , Serviços Preventivos de Saúde/legislação & jurisprudência , Planos Governamentais de Saúde/legislação & jurisprudência , Estados UnidosAssuntos
Diabetes Mellitus/prevenção & controle , Promoção da Saúde , Estilo de Vida , Planos Governamentais de Saúde , Centers for Disease Control and Prevention, U.S. , Diabetes Mellitus/reabilitação , Educação em Saúde , Humanos , Minnesota , Equipe de Assistência ao Paciente , Apoio à Pesquisa como Assunto , Estados UnidosRESUMO
American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice are systematically developed statements to assist health-care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. The American Society for Parenteral & Enteral Nutrition fully endorses sections of these guidelines that address the metabolic and nutritional management of the bariatric surgical patient.
Assuntos
Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Assistência Perioperatória/métodos , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/psicologia , Trato Gastrointestinal/metabolismo , Humanos , Apoio Nutricional/métodos , Seleção de Pacientes , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapiaRESUMO
When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia. These are the most common metabolic diseases managed by clinicians and are all major cardiovascular disease risk factors. 'Disease' is traditionally characterized as anatomic and physiologic abnormalities of an organ or organ system that contributes to adverse health consequences. Using this definition, pathogenic adipose tissue is no less a disease than diseases of other body organs. This review describes the consequences of pathogenic fat cell hypertrophy and visceral adiposity, emphasizing the mechanistic contributions of genetic and environmental predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte factors and inflammation. Appreciating the full pathogenic potential of adipose tissue requires an integrated perspective, recognizing the importance of 'cross-talk' and interactions between adipose tissue and other body systems. Thus, the adverse metabolic consequences that accompany fat cell hypertrophy and visceral adiposity are best viewed as a pathologic partnership between the pathogenic potential adipose tissue and the inherited or acquired limitations and/or impairments of other body organs. A better understanding of the physiological and pathological interplay of pathogenic adipose tissue with other organs and organ systems may assist in developing better strategies in treating metabolic disease and reducing cardiovascular disease risk.