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OBJECTIVE: In patients undergoing bariatric surgery or medical management for obesity, we assessed whether those experiencing substantial weight loss had changes in innervated knee structures or in cartilage. METHODS: Severely obese patients (body mass index (BMI) ≥35) with knee pain on most days were seen before bariatric surgery or medical weight management and at 1-year follow-up. Examinations included 3T MRI acquired at both time points for semi-quantitative scoring of bone marrow lesions (BML), synovitis, cartilage damage, and for quantitative measurement of cartilage thickness. Association of ≥20% vs <20% weight loss with change in semi-quantitative scores was evaluated using linear mixed-effects models, and that with cartilage thickness change used non-parametric and parametric methods. Sensitivity analyses tested different thresholds for weight loss, weight loss as a continuous measure, examined those with and without bariatric surgery, and with worse osteoarthritis (OA). RESULTS: 75 subjects (median age 49 years, 92% women) were included. At baseline, 61 subjects (81%) had Kellgren and Lawrence (KL) grade >0, and 16 (21%) had KL grade ≥3; 69 (92%) had cartilage damage. For BML, synovitis, and cartilage damage, the majority of knees had change in semi-quantitative scores of 0, and there was no difference between those with and without ≥20% weight loss. Similarly, in terms of cartilage thickness loss, in 14 of 16 sub-regions thickness loss was not associated with weight loss. Sensitivity analyses showed similar findings. CONCLUSION: In middle-aged persons with mostly mild radiographic OA, structural features changed little over a year and weight loss was not associated with effects on structural changes.
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Obesidade Mórbida/terapia , Osteoartrite do Joelho/patologia , Redução de Peso , Adulto , Cirurgia Bariátrica , Cartilagem Articular/patologia , Feminino , Humanos , Articulação do Joelho/inervação , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Osteoartrite do Joelho/complicações , Fatores de TempoRESUMO
OBJECTIVE: Excess weight is a known risk factor for functional limitation and common in adults with knee osteoarthritis (OA). We asked to what extent high waist circumference was linked with developing difficulty with walking speed and distance over 4 years in adults with or at risk of knee OA. METHOD: Using data from the Osteoarthritis Initiative (OAI), we employed World Health Organization (WHO) categories for Body Mass Index (BMI) and waist circumference (small/medium and large). Difficulty with speed was defined by slow gait: <1.2 m/s during a 20-m walk, and difficulty with distance was defined by an inability to walk 400 m. We calculated risk ratios (RR) to examine the likelihood of developing difficulty with distance and speed using obesity and waist circumference as predictors with RRs adjusted for potential confounders (i.e., age, sex, race, education, physical activity, and OA status). RESULTS: Participants with obesity and large waists were 2.2 times more likely to have difficulty with speed at 4 years compared to healthy weight and small/medium waisted participants (Adjusted RR 2.2 [95% Confidence interval (CI) 1.6, 3.1], P < .0001). Participants with obesity and a large waist circumference had 2.4 times the risk of developing the inability to walk 400 m compared with those with a healthy BMI and small/medium waist circumference (Adjusted RR 0.9 [95% CI 1.6, 3.7], P < .0001). CONCLUSIONS: Waist circumference may be a main risk factor for developing difficulty with speed in adults with or at risk of knee OA.
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Osteoartrite do Joelho/complicações , Circunferência da Cintura , Caminhada , Índice de Massa Corporal , Feminino , Humanos , Locomoção , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fatores de RiscoRESUMO
Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety. Thus, metformin should be considered for a treatment indication in patients with these conditions.
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Fármacos Antiobesidade/uso terapêutico , Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/efeitos adversos , Doenças Cardiovasculares , Diabetes Mellitus/prevenção & controle , Humanos , Metformina/efeitos adversos , Neoplasias , Obesidade/terapia , Redução de Peso/efeitos dos fármacosRESUMO
Body composition was determined using dual-energy X-ray absorptiometry (DXA) in a subset of patients without (BLOSSOM) and with (BLOOM-DM) type 2 diabetes who received diet and exercise counselling along with either lorcaserin 10 mg twice daily or placebo. DXA scans were performed on study day 1 (baseline), week 24 and week 52. Baseline demographics of the subpopulations (without diabetes, n = 189; with diabetes, n = 63) were similar between studies and representative of their study populations. At week 52, patients without diabetes on lorcaserin lost significantly more fat mass relative to those on placebo (-12.06% vs -5.93%; p = 0.008). In patients with diabetes, fat mass was also decreased with lorcaserin relative to placebo (-9.87% vs -1.65%; p < 0.05). More fat mass was lost in the trunk region with lorcaserin compared with placebo (without diabetes: -3.31% vs -2.05%; with diabetes: -3.65% vs -0.36%). Weight loss with lorcaserin was associated with a greater degree of fat mass loss than lean mass loss, and most of the fat mass lost for patients without and with diabetes was from the central region of the body.
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Tecido Adiposo/diagnóstico por imagem , Benzazepinas/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Dietoterapia , Terapia por Exercício , Obesidade/terapia , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Absorciometria de Fóton , Adulto , Composição Corporal , Estudos de Casos e Controles , Terapia Combinada , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/metabolismo , Sobrepeso/terapia , Receptor 5-HT2C de SerotoninaRESUMO
OBJECTIVE: To review how bariatric surgery in obese patients may effectively treat adiposopathy (pathogenic adipose tissue or 'sick fat'), and to provide clinicians a rationale as to why bariatric surgery is a potential treatment option for overweight patients with type 2 diabetes, hypertension, and dyslipidaemia. METHODS: A group of clinicians, researchers, and surgeons, all with a background in treating obesity and the adverse metabolic consequences of excessive body fat, reviewed the medical literature regarding the improvement in metabolic disease with bariatric surgery. RESULTS: Bariatric surgery improves metabolic disease through multiple, likely interrelated mechanisms including: (i) initial acute fasting and diminished caloric intake inherent with many gastrointestinal surgical procedures; (ii) favourable alterations in gastrointestinal endocrine and immune responses, especially with bariatric surgeries that reroute nutrient gastrointestinal delivery such as gastric bypass procedures; and (iii) a decrease in adipose tissue mass. Regarding adipose tissue mass, during positive caloric balance, impaired adipogenesis (resulting in limitations in adipocyte number or size) and visceral adiposity are anatomic manifestations of pathogenic adipose tissue (adiposopathy). This may cause adverse adipose tissue endocrine and immune responses that lead to metabolic disease. A decrease in adipocyte size and decrease in visceral adiposity, as often occurs with bariatric surgery, may effectively improve adiposopathy, and thus effectively treat metabolic disease. It is the relationship between bariatric surgery and its effects upon pathogenic adipose tissue that is the focus of this discussion. CONCLUSIONS: In selective obese patients with metabolic disease who are refractory to medical management, adiposopathy is a surgical disease.
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Adiposidade , Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Análise Custo-Benefício , Humanos , Estilo de Vida , Doenças Metabólicas/terapia , Obesidade/patologia , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Fatores de Risco , Resultado do Tratamento , Redução de PesoRESUMO
INTRODUCTION: The elderly population is projected to be the fastest growing group of individuals with obesity group in the United States. As such, there is merit in examining factors that contribute to healthy aging and weight management. The effects of newer weight loss medications approved after 2013 have been studied but are not often assessed specifically in older persons. METHODS: This post hoc analysis evaluated the magnitude of weight loss in adults across age quartiles with lorcaserin, a serotonin (5-HT) 2C receptor agonist indicated as an adjunct to a reduced-caloric diet and increased physical activity for chronic weight management. Data from three lorcaserin pivotal phase 3 studies were used in this analysis. Data for patients with overweight/obesity without type 2 diabetes (T2D; BLOOM/BLOSSOM; body mass index [BMI] 27.0-29.9 kg/m2 and ≥1 comorbidity or BMI 30.0-45.0 kg/m2) and patients with overweight/obesity with T2D (BLOOM-DM; BMI 27.0-45.0 kg/m2) were used. Patients were randomized to receive lorcaserin 10 mg twice daily or placebo in addition to diet and exercise for 52 weeks. Age quartiles between the studies differed as the T2D population was on average, 9 years older. RESULTS: This analysis shows that lorcaserin was associated with improved weight loss relative to placebo regardless of age. Importantly, these results were consistent for patients with and without T2D. Interestingly, the magnitude of weight loss for lorcaserin appeared to increase with increasing age. In patients without T2D, odds of achieving ≥5% and ≥10% reduction in body weight at 52 weeks were significantly higher for patients >36 years. Lorcaserin was well tolerated in all patients across all quartiles including the oldest quartile. CONCLUSIONS: In summary, this post hoc analysis demonstrates that lorcaserin treatment in patients with and without T2D was safe and effective at reducing weight across all age groups analysed. Weight loss appeared to be greater for older patients; additional analyses are warranted to confirm these findings and to better understand the factors for improved weight loss.
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Objective: Minimal risk weight loss tools are needed. This study's objective was to confirm Food and Drug Administration submissions of the SmartByte™ System's safety and efficacy. Methods: This 16-week, prospective, single-arm, four-centre, observational study assessed the oral device in combination with a video-delivered lifestyle programme in adults aged 18-49 years with body mass index 27 to <35 kg m-2. Results: Seventy-six subjects received the device and video lifestyle instruction. The prespecified per protocol (PP) population (N = 40) required sensor-verified use of the device ≥7 times per week for 14 of 16 weeks, overall device usage rate of ≥33% and study completion. At week 16, 12 (30%) achieved ≥5% weight loss, 16 (40%) achieved ≥4% and 21 (52.5%) achieved ≥3%. Week 16 mean loss for the PP population was 2.93%, and among 36 participants who did not meet PP criteria, it was 1.45%. Among 76 intent-to-treat subjects, two subjects reported three mild to moderate device-related adverse events, resolving spontaneously (one hard palate abrasion and two tongue lacerations). Conclusion: The System, a minimal risk tool, can help individuals achieve meaningful weight loss, when used with a lifestyle video. More frequent device use was associated with more weight loss, on average, and greater chance of achieving ≥4% or ≥5% weight loss.
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OBJECTIVES: Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. DESIGN: Randomized, double-blind, placebo-controlled six-month intervention trial. SETTING: Participants were recruited from Boston MA USA and surrounding communities. PARTICIPANTS: Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. INTERVENTION: Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. RESULTS: A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. CONCLUSION: This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.
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Ingestão de Energia/fisiologia , Limitação da Mobilidade , Estado Nutricional/fisiologia , Sarcopenia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Humanos , MasculinoRESUMO
Plasma amino acids were measured in 17 postoperative subjects randomly assigned to receive for > or = 5 d tube feeding or total parenteral nutrition (TPN) that had identical energy, nitrogen, and glutamine contents. Subjects required gastric or pancreatic surgery for malignancy and were well-matched for age and body mass index. Tube feeding or TPN began on postoperative day 1 and advanced in daily 25% increments to meet goals of 105 kJ . kg body wt-1 . d-1, 1.5 g protein . kg body wt-1 . d-1, and 0.3 g glutamine . kg body wt-1 . d-1. Delivered energy, nitrogen, and glutamine were closely matched on day 4. Nitrogen balance and plasma proteins did not differ significantly between feeding groups. Total indispensable amino acids, branched-chain amino acids, and glutamine declined 25% on postoperative day 1 compared with preoperative day 0. Indispensable and branched-chain amino acid concentrations were restored with 5 d of either tube feeding or TPN. Glutamine concentrations did not differ significantly by feeding group, though a trend suggested that glutamine recovered more slowly in the tube-fed than in the TPN-fed subjects. Plasma amino acids otherwise reflected formula composition with ratios of valine to leucine of 1.24 and 3.69 mumol/L in subjects receiving 5 d of tube feeding or TPN, respectively. These findings suggest that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses.
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Aminoácidos/sangue , Nutrição Enteral/normas , Alimentos Formulados/normas , Glutamina/farmacologia , Nutrição Parenteral/normas , Cuidados Pós-Operatórios/métodos , Adolescente , Adulto , Idoso , Feminino , Alimentos Formulados/análise , Glutamina/administração & dosagem , Glutamina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Nitrogênio/administração & dosagem , Nitrogênio/sangue , Nitrogênio/farmacologia , Pâncreas/cirurgia , Estômago/cirurgiaRESUMO
A recent study demonstrated that the incidence of new arrhythmias occurring during central venous catheter insertion or exchange was 41% atrial and 25% ventricular arrhythmias (12% couplets or greater). Over-insertion of the guidewire, causing direct stimulation to the right side of the heart, has been postulated to be the causative factor. A new technique that allows the operator to control the length of guidewire inserted was developed. With this technique on a population of hospitalized patients, similar to those in the previous study, the incidence of atrial arrhythmias decreased to 32% and the incidence of ventricular arrhythmias to 6% (single premature ventricular contractions only). Although this new technique has limitations, there was a dramatic improvement in the incidence of cardiac arrhythmias. These results indicate a need for modifications in the available equipment to avoid the infrequent but life-threatening complication of malignant arrhythmia.
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Arritmias Cardíacas/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Nutrição Parenteral Total , Arritmias Cardíacas/etiologia , Estatura , HumanosRESUMO
The risk of complication during the insertion or exchange of central venous catheters has been well documented. The majority of complications involve mechanical problems associated with insertion. Although cardiac arrhythmia has been acknowledged as a possible complication, its incidence has never been quantified. We performed cardiac monitoring on patients during 51 central venous catheter insertions or exchanges to determine the incidence of cardiac arrhythmias during guidewire insertion. Forty-one percent of procedures resulted in atrial arrhythmias and 25% produced some degree of ventricular ectopy, 30% of these were ventricular couplets or greater. Ventricular ectopy was significantly more common in shorter patients (160 +/- 8 vs 168 +/- 11 cm, p less than 0.05) and when the catheter was inserted from the right subclavian position (43% ventricular ectopy vs 10% at the other sites). Other variables such as age, cardiac history, serum potassium, type of procedure, and catheter brand were not significant. It is our conclusion that over-insertion of the wire causes this cardiac stimulation. Despite the absence of morbidity or mortality in this study, this incidence of ventricular ectopy indicates that there is a distinct possibility of a malignant arrhythmia being precipitated by a guidewire. Some modification of the current protocol for these procedures seems indicated.
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Arritmias Cardíacas/etiologia , Cateterismo Venoso Central/efeitos adversos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Estatura , Cateterismo Venoso Central/instrumentação , Eletrocardiografia , Falha de Equipamento , Humanos , Incidência , Monitorização Fisiológica , Nutrição ParenteralRESUMO
The statistics are staggering: 59.4% of men, 50.7% of women, and 54.9% of the total population are overweight. Consequently, heightened efforts are being directed to control this epidemic. Clinicians have shown a renewed interest in the use of appetite suppressants and other antiobesity agents concomitantly with conventional treatment of diet education, exercise training, and lifestyle modification. This article reviews appetite suppressants both from a historical perspective and currently, and then presents a rationale for the continued use of antiobesity agents in the management of obesity.
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Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Índice de Massa Corporal , Ciclobutanos/administração & dosagem , Feminino , Seguimentos , Humanos , Lactonas/administração & dosagem , Masculino , Obesidade/diagnóstico , Orlistate , Fentermina/administração & dosagem , Redução de PesoRESUMO
BACKGROUND: A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity. OBJECTIVE: To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat. METHODS: We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMIî¶30 kg m(-2)) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS(+) or CLS(-) based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLSs), omental (CLSo) and mesenteric (CLSm) adipose depots. RESULTS: The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS(+)) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS(+) status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved. CONCLUSIONS: In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.
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There is a huge void in the current pharmacological treatment options for obesity. This gap is surprising given the high prevalence and associated costs of obesity. Many factors have prevented active drug development, including the poor safety and efficacy of earlier antiobesity drugs. However, there are now several compelling targets on the horizon. The new generation of antiobesity drugs offers hope for the management of obesity, but no single agent is likely to be a panacea. Rather, obesity will need to be managed like many other chronic diseases, with combination therapies and long-term treatment in order to achieve sustained success. New targets have arisen as more research has been performed to understand the complex circuitry that controls energy homeostasis. The goal of this review is to discuss the latest pharmacological agents and strategies that are under development and that may eventually be used for the treatment of obesity.