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OBJECTIVE: Obesity-related problems can now be managed with effective nutritional therapy, pharmacotherapy, and surgeries that achieve >10% weight loss. Assessing patient preferences, treatment choices, and factors affecting patients can improve treatment compliance and efficacy. Our aim was to identify factors affecting patient preference and subsequent choice of pharmacotherapy among those seeking treatment for obesity-related disorders. METHODS: A participatory action study using purposeful sampling recruited 33 patients with obesity complications. They were referred to specialist clinics in non-alcoholic fatty liver disease, diabetes mellitus, hypertension, and chronic kidney disease. Sixteen males and seventeen females aged 18-70 years, with BMI > 35 kg/m2 were recruited. Before the interview, participants watched a 60-minute video explaining nutritional therapy, pharmacotherapy, and surgery in equipoise. Data were collected in semi-structured interviews; Reflective thematic analysis was used. This sub study focuses only on patients who expressed specific attitudes (positive or negative) towards pharmacotherapy. RESULTS: Ten (30%) patients expressed a view on pharmacotherapy. Eight (24%) patients chose pharmacotherapy alone, whereas two (6%) patients chose pharmacotherapy combined with nutritional therapy. In this sub study focusing on pharmacotherapy, five themes were identified related to choosing whether or not to take medication: (1) attitudes towards pharmacotherapy, (2) attitudes toward size of obesity and its complications, (3) weighing the benefits and risks of treatment, (4) knowledge and reassurance of health professionals, and (5) costs associated with drug therapy. CONCLUSION: The primary concerns regarding pharmacotherapy for intentional weight loss were efficacy, side effects, lifelong dosing, pharmacokinetics, and cost. Providing access to information about all the pharmacotherapies and the benefits is likely to result in greater penetrance of treatment.
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BACKGROUND: Bariatric surgery reduces incidence of albuminuria and end-stage renal disease in patients with obesity. Effects of bariatric surgery on long-term remission and progression of pre-existing obesity-related renal damage are mainly unexplored. Here we investigate the long-term effects of bariatric surgery compared with conventional obesity care on remission and progression of albuminuria. METHODS: 4047 patients were included in the Swedish Obese Subjects study. Inclusion criteria were age 37-60 years, BMI ≥ 34 kg/m2 in men and BMI ≥ 38 kg/m2 in women. Our analysis comprised 803 patients (19.8% of total population, 357 control, 446 surgery) with pre-existing albuminuria including 693 patients (312 control, 381 surgery) with microalbuminuria, and 110 patients (45 control, 65 surgery) with macroalbuminuria. Surgery patients were treated with banding, vertical banded gastroplasty, or gastric bypass. Control patients received conventional obesity care. RESULTS: Total urinary albumin excretion was 36.5% lower in all patients with albuminuria after 15 years, 44.5% lower in patients with microalbuminuria after 15 years, and 27.8% lower in patients with macroalbuminuria after 2 years following bariatric surgery compared with conventional care. In surgery patients with microalbuminuria, remission to normoalbuminuria was higher (OR, 5.9, 2.2, 3.2, p < 0.001) and progression to macroalbuminuria was lower (OR, 0.28, 0.26, 0.25, p ≤ 0.02) at 2, 10, and 15 years, respectively, compared with control patients. In surgery patients with macroalbuminuria remission to normo- or microalbuminuria was higher (OR, 3.67, p = 0.003) after 2 years. No differences between surgery and control patients with macroalbuminuria were observed after 10 and 15 years. Surgery slowed progression of eGFR decline after 2 years in patients with microalbuminuria and macroalbuminuria (treatment effect: 1.0 ml/min/1.73 m2/year, p = 0.001 and 1.4 ml/min/1.73 m2/year, p = 0.047, respectively). CONCLUSION: Bariatric surgery had better effects than conventional obesity care on remission of albuminuria and prevention of eGFR decline, indicating that patients with obesity-related renal damage benefit from bariatric surgery.
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Albuminúria , Cirurgia Bariátrica/estatística & dados numéricos , Falência Renal Crônica , Obesidade , Adulto , Albuminúria/complicações , Albuminúria/epidemiologia , Albuminúria/fisiopatologia , Progressão da Doença , Feminino , Humanos , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Suécia , Resultado do TratamentoRESUMO
Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.
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Esofagectomia , Esvaziamento Gástrico , Estudos Transversais , Peptídeo 1 Semelhante ao Glucagon , Humanos , Masculino , Período Pós-PrandialRESUMO
AIM: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people. METHODS: A 1-day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes. RESULTS: Workshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery). CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.
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Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/terapia , Dietoterapia , Exercício Físico , Incretinas/uso terapêutico , Estilo de Vida , Indução de Remissão/métodos , Pesquisa Biomédica , Humanos , Ciência da Implementação , Medicina de Precisão , Pesquisa , Reino UnidoRESUMO
BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.
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Esofagectomia , Hormônios Gastrointestinais/sangue , Hipoglicemia/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Composição Corporal , Feminino , Seguimentos , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/fisiopatologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Prandial , Estudos Prospectivos , Resposta de Saciedade , Redução de PesoRESUMO
BACKGROUND: Obesity is a major public health problem leading to co-morbidities such as diabetes, hypertension and kidney failure. Bariatric surgery results in pronounced and maintained weight loss and prevention of obesity-related diseases and their complications. Most studies of bariatric surgery on kidney disease show improvements after surgery. However, long-term studies analyzing hard end-points are lacking. Here we report on the long-term effects of bariatric surgery compared to usual obesity care on incidence of end-stage renal disease (ESRD) alone and in combination with chronic kidney disease stage 4 (CKD4/ESRD). METHODS: 4047 patients were included in the Swedish Obese Subjects (SOS) study. Inclusion criteria were age 37-60 years and BMI ≥ 34 in men and BMI ≥ 38 in women. Patients in the bariatric surgery group (N = 2010) underwent banding (18%), vertical banded gastroplasty (69%), or gastric bypass (13%); controls (N = 2037) received usual obesity care. In this analysis, patients were followed up for a median time of 18 years. The incidence of ESRD and CKD4 was obtained by crosschecking the SOS database with the Swedish National Patient Register. RESULTS: During follow-up, ESRD occurred in 13 patients in the surgery group and in 26 patients in the control group (adjusted hazard ratio (HR) = 0.27; 95% CI 0.12-0.60; p = 0.001). The number of CKD4/ESRD events was 23 in the surgery group and 39 in the control group (adjusted HR = 0.33; 95% CI 0.18-0.62; p < 0.001). In both analyses, bariatric surgery had a more favorable effect in patients with baseline serum insulin levels above median compared to those with lower insulin levels (interaction p = 0.010). Treatment benefit of bariatric surgery was also greater in patients with macroalbuminuria at baseline compared to those without macroalbuminuria (interaction p < 0.001). CONCLUSIONS: Our study showed for the first time that bariatric surgery is associated with a long-term protection against ESRD and CKD4/ESRD.
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Cirurgia Bariátrica/efeitos adversos , Falência Renal Crônica/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Cirurgia Bariátrica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Suécia/epidemiologiaRESUMO
BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.
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Gastroplastia , Laparoscopia , Síndrome Metabólica/cirurgia , Obesidade Mórbida/cirurgia , Redução de Peso , Austrália , Índice de Massa Corporal , Feminino , Seguimentos , Gastroplastia/métodos , Humanos , Laparoscopia/métodos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Estudos Prospectivos , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
Since the publication of the above article it has been noted that the author S O'Brien should have been listed as CS O'Brien. The authors should therefore appear as follows: R Dutia, M Embrey, CS O'Brien, RA Haeusler, KK Agénor, P Homel, J McGinty, RP Vincent, J Alaghband-Zadeh, B Staels, CW le Roux, J Yu and B Laferrère The corrected article html and online pdf versions have been amended. The authors wish to apologise for any inconvenience caused.
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AIMS: Liraglutide 3.0 mg, an acylated GLP-1 analogue approved for weight management, lowers body weight through decreased energy intake. We conducted exposure-response analyses to provide important information on individual responses to given drug doses, reflecting inter-individual variations in drug metabolism, absorption and excretion. METHODS: We report efficacy and safety responses across a wide range of exposure levels, using data from one phase II (liraglutide doses 1.2, 1.8, 2.4 and 3.0 mg), and two phase IIIa [SCALE Obesity and Prediabetes (3.0 mg); SCALE Diabetes (1.8; 3.0 mg)] randomized, placebo-controlled trials (n = 4372). RESULTS: There was a clear exposure-weight loss response. Weight loss increased with greater exposure and appeared to level off at the highest exposures associated with liraglutide 3.0 mg in most individuals, but did not fully plateau in men. In individuals with overweight/obesity and comorbid type 2 diabetes, there was a clear exposure-glycated haemoglobin (HbA1c) relationship. HbA1c reduction increased with higher plasma liraglutide concentration (plateauing at â¼21 nM); however, for individuals with baseline HbA1c >8.5%, HbA1c reduction did not fully plateau. No exposure-response relationship was identified for any safety outcome, with the exception of gastrointestinal adverse events (AEs). Individuals with gallbladder AEs, acute pancreatitis or malignant/breast/benign colorectal neoplasms did not have higher liraglutide exposure compared with the overall population. CONCLUSIONS: These analyses support the use of liraglutide 3.0 mg for weight management in all subgroups investigated; weight loss increased with higher drug exposure, with no concomitant deterioration in safety/tolerability besides previously known gastrointestinal side effects.
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Depressores do Apetite/administração & dosagem , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Incretinas/administração & dosagem , Liraglutida/administração & dosagem , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Depressores do Apetite/efeitos adversos , Depressores do Apetite/farmacocinética , Depressores do Apetite/uso terapêutico , Índice de Massa Corporal , Estudos de Coortes , Terapia Combinada/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Dieta Redutora , Relação Dose-Resposta a Droga , Método Duplo-Cego , Exercício Físico , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Incretinas/efeitos adversos , Incretinas/farmacocinética , Incretinas/uso terapêutico , Liraglutida/efeitos adversos , Liraglutida/farmacocinética , Liraglutida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/terapia , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/terapia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/terapia , Caracteres Sexuais , Redução de Peso/efeitos dos fármacosRESUMO
Obesity is associated with significant complications and healthcare costs, but our ability to treat obesity has been limited by our understanding of its pathogenesis. We surveyed diabetologists and obesity related health care professionals asking them which organ they believed to be responsible for the pathogenesis of obesity. Participants favoured a central nervous system (CNS) aetiology. The response echoes evidence from genome wide association studies identifying a link between obesity and CNS loci. Our most successful obesity therapies involve the manipulation of subcortical area of the brain involved in energy balance. Future success in the management of obesity will be determined by our ability to define the pathogenesis of the disease in individual cases, moving from a one-size-fits-all, to more focused interventions.
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BACKGROUND/OBJECTIVES: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. SUBJECTS/METHODS: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. RESULTS: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. CONCLUSIONS: The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.
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Anastomose em-Y de Roux/métodos , Hormônios Gastrointestinais/metabolismo , MicroRNAs/metabolismo , Neuropeptídeos/metabolismo , Obesidade/metabolismo , Animais , Glicemia , Modelos Animais de Doenças , Metabolismo Energético , Masculino , Fenótipo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Redução de PesoRESUMO
INTRODUCTION: Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM. METHODS: Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM. RESULTS: A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found. CONCLUSIONS: This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.
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Ácidos e Sais Biliares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Derivação Gástrica , Hidroxilação , Obesidade Mórbida/cirurgia , Redução de Peso , Adulto , Jejum/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Peptídeo YY/metabolismo , Período Pós-Operatório , Período Pós-Prandial , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of ß-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.
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Fármacos Antiobesidade/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Comportamento Alimentar , Hemoglobinas Glicadas/metabolismo , Obesidade Mórbida/terapia , Redução de Peso , Cirurgia Bariátrica/métodos , Benzazepinas/uso terapêutico , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Frutose/análogos & derivados , Frutose/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Glucosídeos/uso terapêutico , Homeostase , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/uso terapêutico , Lactonas/uso terapêutico , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Obesidade Mórbida/sangue , Obesidade Mórbida/prevenção & controle , Orlistate , Fentermina/uso terapêutico , Receptores de Glucagon/efeitos dos fármacos , Topiramato , Resultado do TratamentoRESUMO
BACKGROUND: Roux-en-Y gastric bypass may lead to impaired calcium uptake. Therefore, operation-specific effects of gastric bypass and vertical banded gastroplasty on bone mineral density (BMD) were examined in a randomized clinical trial. Bone resorption markers and mechanisms of decreased calcium uptake after gastric bypass were investigated using blood and endoscopic samples from two additional patient cohorts. METHODS: Total BMD and non-weight-bearing skull BMD were measured by dual-energy X-ray absorptiometry at baseline, and 1 and 6 years after gastric bypass or vertical banded gastroplasty in patients who were not receiving calcium supplements. Bone resorption markers in serum and calcium uptake mechanisms in jejunal mucosa biopsies were analysed after gastric bypass by proteomics including radioimmunoassay, gel electrophoresis and mass spectrometry. RESULTS: One year after surgery, weight loss was similar after gastric bypass and vertical banded gastroplasty. There was a moderate decrease in skull BMD after gastric bypass, but not after vertical banded gastroplasty (P < 0·001). Between 1 and 6 years after gastric bypass, skull BMD and total BMD continued to decrease (P = 0·001). C-terminal telopeptide levels in serum had increased twofold by 18 months after gastric bypass. Proteomic analysis of the jejunal mucosa revealed decreased levels of heat-shock protein 90ß, a co-activator of the vitamin D receptor, after gastric bypass. Despite increased vitamin D receptor levels, expression of the vitamin D receptor-regulated calcium transporter protein TRPV6 decreased. CONCLUSION: BMD decreases independently of weight after gastric bypass. Bone loss might be attributed to impaired calcium absorption caused by decreased activation of vitamin D-dependent calcium absorption mechanisms mediated by heat-shock protein 90ß and TRPV6.
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Densidade Óssea/fisiologia , Cálcio/metabolismo , Intestino Delgado/metabolismo , Peso Corporal , Reabsorção Óssea/metabolismo , Canais de Cálcio/fisiologia , Feminino , Derivação Gástrica/efeitos adversos , Gastroplastia/efeitos adversos , Humanos , Absorção Intestinal/fisiologia , Masculino , Glicoproteínas de Membrana/fisiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Estudos Prospectivos , Receptores de Calcitriol/fisiologia , Canais de Cátion TRPV/fisiologiaRESUMO
The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) have introduced specific criteria to define the 'optimization' of the metabolic state and glycaemic 'remission' of type 2 diabetes mellitus (T2DM) after bariatric surgery, respectively. Our objective was to assess the percentage of patients achieving these criteria. Data were collected for body mass index, glycaemic markers, lipids, blood pressure, hypoglycaemia and medication usage from 396 morbidly obese T2DM patients who underwent bariatric surgery in two centres and followed up for 2 years. At year 1, 14% of patients achieved the IDF criteria and 38% the ADA criteria, whereas at 2 years 8 and 9% satisfied these criteria, respectively. A relatively low proportion of patients achieved optimization of the metabolic state and T2DM remission. These patients may potentially benefit from the combination of bariatric surgery and adjuvant medical therapy to achieve optimal metabolic outcomes.
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Cirurgia Bariátrica , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Obesidade Mórbida/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Indução de Remissão , Medição de Risco , Resultado do Tratamento , Redução de PesoRESUMO
As well as the pronounced effect on body mass index (BMI), bariatric surgery is increasingly recognized as being associated with improvements in morbidity and mortality in a range of conditions, from airways disease to cancer. In metabolic disease, the impact of bariatric surgery is particularly obvious with marked improvements in glycemic control in patients with type 2 diabetes mellitus, to the point of effecting diabetes remission in some. Hypertension and dyslipidemia, key components of the metabolic syndrome, also respond to bariatric surgery. Despite the increasing evidence of benefit in metabolic disease, the major national guidelines for selecting candidates for bariatric surgery retain their emphasis on body weight. In these guidelines, a BMI ≥35 kg/m(2) is needed to indicate surgery, even in those with profound metabolic disturbance. The recent International Diabetes Federation guidelines have identified the need to reorientate our focus from BMI to metabolic disease. In this review, we examine the developing indications for the use of bariatric surgery in metabolic disease. We will focus on type 2 diabetes mellitus and the metabolic syndrome. Within this, we will outline the data for using bariatric surgery as metabolic surgery, including those with a BMI <35 kg/m(2).
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Cirurgia Bariátrica , Síndrome Metabólica/cirurgia , Obesidade/cirurgia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Humanos , Síndrome Metabólica/complicações , Obesidade/complicações , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: The metabolic effects of gastrectomy and the reduction of visceral adiposity through omentectomy for gastric cancer are unknown. METHODOLOGY: We retrospectively reviewed of prospectively collected data of 67 patients over one year who underwent radical gastrectomy with either a complete or partial omentectomy for gastric cancer. The change in Body mass index (BMI), triglyceride, low density lipoprotein, high density lipoprotein, and hematological profile were evaluated. RESULTS: In the group of 67 patients changes were observed after 1 year follow-up for BMI (23.7±3.1 versus 21.3±2.5kg/m2; p<0.001), triglyceride (155.2±136.1 versus 89.7±41.2mg/dL, p=0.011), low density lipoprotein (107.4±45.4 versus 95.8±27.5mg/dL, p=0.020), vitamin B12 (681.4±297.4 versus 558.1±338.6pg/mL, p=0.076). High density lipoprotein (41.4±12.6 versus 52.8±10.5mg/dL) increased after surgery (p<0.001). There were no changes between the complete and partial omentectomy groups for BMI, albumin, triglyceride, lipoprotein, and hemoglobin. CONCLUSIONS: Gastrectomy with or without omentectomy induced a decrease of BMI and improvements in metabolic parameters such as triglyceride, low density lipoprotein, high density lipoprotein. Omentectomy had no significant impact on any measured parameter in this group.
Assuntos
Gastrectomia , Gordura Intra-Abdominal/cirurgia , Omento/cirurgia , Neoplasias Gástricas/cirurgia , Adiposidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Hematopoese , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The King's Obesity Staging system was developed to evaluate the effect of obesity treatments in multiple physical, psychological and functional domains. In this prospective cohort study, a Northern Irish cohort was scored using the King's Obesity Staging system before and 1 year after bariatric surgery. 71 individuals underwent surgery and 31 (44%) had type 2 diabetes. Bariatric surgery improved each health domain (p < 0.05). A subgroup with type 2 diabetes showed a significantly greater improvement in gonadal disease (polycystic ovarian syndrome and sub-fertility) (p = 0.02), and a trend towards greater improvement in cardiovascular disease (p = 0.07) compared with the non-diabetic subgroup. Half of those with pre-diabetes were normoglycaemic postoperatively (p < 0.05). The King's Obesity Staging system can be used to holistically evaluate the outcomes of bariatric surgery. Patients benefit from bariatric surgery in many ways, but those with diabetes may benefit more.
Assuntos
Cirurgia Bariátrica , Nível de Saúde , Adulto , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/cirurgia , Síndrome do Ovário Policístico/epidemiologia , Resultado do TratamentoRESUMO
Background: It is anticipated that by 2030, 20% of the world's population will live with obesity. Success in the management of obesity is predominately determined in terms of BMI or percentage weight loss, yet the limitations of these have been widely recognized. This study aimed to understand patient definitions of success in obesity treatment. Methods: A series of in-depth focus groups, carried out with n = 30 adults living with obesity, offered a qualitative insight into patient definitions of success. Results: A thematic analysis of data yielded four thematic findings: Success as freedom from stigma, bias and the mental burden of obesity; success as being able to participate fully in the world; success as measured by NSVs [non-scale victories]; and success is not a number on a scale. Conclusions: What this study highlights is (1) how current measures of success do not accurately encompass the priorities of people living with obesity, (2) the importance of addressing the psychological and emotional aspects of living with obesity in any definition of success , and (3) the importance of meaningful co-creation of goals and indicators of success between clinician and patient for the effective management of the disease of obesity.