RESUMO
INTRODUCTION: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. AREAS COVERED: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. EXPERT OPINION: Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.
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Fármacos Antiobesidade/efeitos adversos , Benzazepinas/efeitos adversos , Lactonas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Interações Medicamentosas , Doenças das Valvas Cardíacas/induzido quimicamente , Humanos , Síndromes de Malabsorção/induzido quimicamente , Neoplasias/induzido quimicamente , Orlistate , Síndrome da Serotonina/induzido quimicamente , Estados Unidos , United States Food and Drug AdministrationRESUMO
Obesity is a common and morbid disease, but its treatment remains far from ideal. Many doctors, regulatory agencies, media outlets and patients consider lifestyle modification as the only possible intervention. Pharmacological agents, although with limitations, are useful weapons but are highly stigmatized. Some reasons for this stigma are discussed in this editorial and include: the failure of short-term medication use to achieve long-term results (due to the chronic and recurrent condition of obesity); common perception of obesity as a lifestyle choice; difficulty to treat obesity in the primary care setting; less than desired weight-loss results with medications; misuse of medications for cosmetic reasons; and unfavorable history of other anti-obesity drugs that were withdrawn in previous decades.
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Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Estereotipagem , Fármacos Antiobesidade/efeitos adversos , HumanosRESUMO
Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis. Arq Bras Endocrinol Metab. 2014;58(9):889-99.
O tecido adiposo marrom, órgão essencial para a termorregulação de animais hibernantes e pequenos devido à sua capacidade desacopladora, era até poucos anos considerado presente apenas em recém-nascidos na espécie humana. A identificação do tecido adiposo marrom em adultos com o desenvolvimento e uso da tomografia de emissão de pósitron marcado com 18-fluorodesoxiglicose (PET-FDG) gerou questões sobre sua real importância para nosso metabolismo. Nesta revisão, discutiremos o que aprendemos nesse tempo, assim como conceitos antigos e novos, alguns marginalizados por décadas, como a termogênese induzida por dieta. Arq Bras Endocrinol Metab. 2014;58(9):889-99.
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Adulto , Humanos , Tecido Adiposo Marrom/fisiologia , Canais Iônicos/metabolismo , Proteínas Mitocondriais/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Metabolismo Energético/fisiologia , /farmacocinética , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Termogênese/fisiologiaRESUMO
Estudos longitudinais sugerem que mulheres têm o dobro do risco que os homens de experimentar grandes ganhos de peso ao longo da vida, o que pode estar associado ao maior sedentarismo entre as mulheres, às gestações, à história familiar de obesidade, ao casamento em idade mais jovem e à cessação de tabagismo. O desenvolvimento de estratégias de tratamento e prevenção efetivas para a obesidade requer um melhor entendimento dos determinantes ambientais, comportamentais, sociodemográficos e genéticos do ganho e da manutenção do peso. É importante destacar que, além de avaliar os fatores preditores de obesidade, torna-se também fundamental examinar quais os fatores associados com a manutenção de um peso saudável, pois estes podem ter um importante papel nas estratégias de intervenções preventivas. O objetivo deste artigo é chamar a atenção para o impacto negativo que a obesidade apresenta na saúde da mulher, enfatizando a necessidade, não só de mudanças individuais dietéticas e de estilo de vida, mas também a necessidade de mudanças nas crenças e práticas dos profissionais de saúde diante da obesidade da mulher, que é uma doença muitas vezes ignorada, subdiagnosticada e mal ou incorretamente tratada. Para isso, daremos uma orientação prática para os clínicos gerais sobre como conduzir a avaliação inicial, diagnosticar e tratar a obesidade na mulher.
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O diabetes mellitus é uma doença de importantíssimo impacto populacional, tendo em vista sua alta incidência e sua prevalência crescente ao longo dos últimos anos. Tendo em vista que na maioria dos casos o quadro clínico é muito frustro e os pacientes são pouco sintomáticos, o diagnóstico costuma ser feito muito tardiamente, quando muitas complicações micro e macrovasculares já se instalaram. O tratamento inclui educação, normalização da glicemia, avaliação de complicações macrovasculares e microvasculares, assim como redução de fatores de riscos cardiovasculares.
RESUMO
Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis.
Assuntos
Tecido Adiposo Marrom/fisiologia , Canais Iônicos/metabolismo , Proteínas Mitocondriais/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Adulto , Metabolismo Energético/fisiologia , Fluordesoxiglucose F18/farmacocinética , Humanos , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Termogênese/fisiologia , Proteína Desacopladora 1Assuntos
Masculino , Feminino , Humanos , Medicina Clínica , Obesidade/complicações , Obesidade/prevenção & controle , Saúde PúblicaRESUMO
OBJECTIVE: To evaluate the results of the use of liraglutide in a group of patients undergoing surgical treatment of morbid obesity with unsatisfactory weight loss or regain of more than 15% of minimum reached weight. METHODS: The authors conducted a retrospective analysis of 15 operated patients who had excess weight loss <50% after two years of follow-up or regained weight more than 15% of the minimum reached weight. We included only patients who had the expected "surgical anatomy", assessed by contrast radiography and endoscopy. Mean age was 47.2 ± 12.5 years, and patients received liraglutide at doses from 1.2 to 3.0 mg/day for eight to 28 weeks follow-up. RESULTS: Surgical treatment induced a weight loss of 34.1 ± 16.5 kg. The average weight regain after 5.3 ± 3.3 years was 14.2 ± 12.1 Kg. The average weight was significantly reduced after treatment with liraglutide (100.9 ± 18.3 kg. vs Kg 93.5 ± 17.4, p <0.0001). Six patients had nausea and two discontinued therapy due to the cost of medication. CONCLUSION: medical treatment directed to the control of satiety using liraglutide may be an alternative treatment of patients with poor weight loss or weight regain after surgery when no technical problem has been identified.
Assuntos
Cirurgia Bariátrica , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Obesidade Mórbida/cirurgia , Aumento de Peso , Feminino , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Humanos , Liraglutida , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Falha de TratamentoRESUMO
OBJETIVO: avaliar os resultados da utilização do liraglutide em um grupo de pacientes submetidos ao tratamento cirúrgico da obesidade mórbida com perda insatisfatória de peso ou ganho de mais de 15% do seu peso mínimo atingido. MÉTODOS: realizou-se análise retrospectiva de 15 pacientes operados que tiveram perda de excesso de peso <50% após dois anos de seguimento ou reganho de peso de mais de 15% do peso mínimo atingido. Foram incluídos apenas pacientes que apresentavam a "anatomia cirúrgica" normal avaliada por radiografia contrastada e endoscopia digestiva alta. A média de idade foi 47,2±12,5 anos e os pacientes receberam liraglutide na dose de 1,2 a 3,0mg/dia por oito a 28 semanas de seguimento. RESULTADOS: o tratamento cirúrgico induziu uma perda de peso de 34,1± 16,5Kg. A média de reganho de peso após 5,3 ±3,3 anos foi 14,2±12,1Kg. A media de peso reduziu significativamente após o tratamento com liraglutide (100,9±18,3Kg vs. 93,5±17,4Kg; p<0,0001). Seis pacientes apresentaram náuseas e dois descontinuaram o tratamento em decorrência do custo da medicação. CONCLUSÃO: o tratamento clínico medicamentoso dirigido para o controle da saciedade com o uso do liraglutide pode ser uma alternativa para manejo dos pacientes com reganho de peso ou perda insuficiente após o tratamento cirúrgico, quando nenhum problema técnico tenha sido identificado.
OBJECTIVE: To evaluate the results of the use of liraglutide in a group of patients undergoing surgical treatment of morbid obesity with unsatisfactory weight loss or regain of more than 15% of minimum reached weight. METHODS: The authors conducted a retrospective analysis of 15 operated patients who had excess weight loss <50% after two years of follow-up or regained weight more than 15% of the minimum reached weight. We included only patients who had the expected "surgical anatomy", assessed by contrast radiography and endoscopy. Mean age was 47.2 ± 12.5 years, and patients received liraglutide at doses from 1.2 to 3.0 mg/day for eight to 28 weeks follow-up. RESULTS: Surgical treatment induced a weight loss of 34.1 ± 16.5 kg. The average weight regain after 5.3 ± 3.3 years was 14.2 ± 12.1 Kg. The average weight was significantly reduced after treatment with liraglutide (100.9 ± 18.3 kg. vs Kg 93.5 ± 17.4, p <0.0001). Six patients had nausea and two discontinued therapy due to the cost of medication. CONCLUSION: medical treatment directed to the control of satiety using liraglutide may be an alternative treatment of patients with poor weight loss or weight regain after surgery when no technical problem has been identified.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Bariátrica , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Obesidade Mórbida/cirurgia , Aumento de Peso , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Falha de TratamentoRESUMO
The aim of this article is to focus on the fixed-dose combination of phentermine and topiramate, a new antiobesity drug recently approved by the US FDA. The mechanisms of weight loss for each drug in monotherapy is described, followed by the rationale for its use as a combination therapy and a comprehensive review of recently published clinical trials that assessed its efficacy and safety.
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Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Frutose/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Topiramato , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. SUBJECTS AND METHODS: Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. RESULTS: We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. CONCLUSIONS: The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients.
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Glicemia/análise , Insulina/sangue , Leptina/sangue , Mutação , Obesidade/genética , Receptores para Leptina/genética , Idade de Início , Índice de Massa Corporal , Brasil , Criança , Feminino , Frequência do Gene , Humanos , Masculino , Obesidade/metabolismo , Polimorfismo GenéticoRESUMO
OBJECTIVE: To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. SUBJECTS AND METHODS: Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. RESULTS: We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. CONCLUSIONS: The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients.
OBJETIVO: Analisar o LEPR em crianças obesas e investigar associações entre achados moleculares e características antropométricas e metabólicas. SUJEITOS E MÉTODOS: Foram avaliados 32 pacientes quanto às características antropométricas, à pressão arterial, à frequência cardíaca, às dosagens séricas de glicemia, à insulina, à leptina e ao perfil lipídico. O estudo molecular consistiu na amplificação e no sequenciamento automático da região codificadora do LEPR para pesquisar mutações. RESULTADOS: Identificou-se uma alta prevalência de distúrbios metabólicos: glicemia de jejum alterada em 12,5%, HOMA-IR elevado em 85,7%, níveis de HDL-colesterol baixos em 46,9%, níveis de triglicérides elevados em 40,6% e hipertensão arterial em 58,6%. O estudo molecular identificou 6 variações alélicas já descritas na literatura: rs1137100 (éxon-2), rs1137101 (éxon-4), rs1805134 (éxon-7), rs8179183 (éxon-12), rs1805096 (éxon-18) e deleção/inserção do pentanucleotídeo CTTTA na região 3' não traduzida. CONCLUSÕES: A frequência das variações alélicas observada é semelhante à descrita na literatura e não se correlacionou com nenhuma característica clínica. Os resultados da análise molecular do LEPR não parecem estar implicados na etiologia da obesidade desses pacientes.
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Criança , Feminino , Humanos , Glicemia/análise , Insulina/sangue , Leptina/sangue , Mutação , Obesidade/genética , Receptores para Leptina/genética , Idade de Início , Índice de Massa Corporal , Brasil , Frequência do Gene , Obesidade/metabolismo , Polimorfismo GenéticoRESUMO
BACKGROUND: The objective of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition into the jejunum (JII-SG) or into the duodenum (DII-SG) associated with sleeve gastrectomy for type 2 diabetes mellitus (T2DM) patients with BMI below 35. METHODS: The procedures were performed on 202 consecutive patients. Mean age was 52.2 ± 7.5. Mean duration of T2DM was 9.8 ± 5.2 years. Insulin therapy was used by 41.1%. Dyslipidemia was observed in 78.2%, hypertension in 67.3%, nephropathy in 49.5%, retinopathy in 31.2%, coronary heart disease in 11.9%, and other cardiovascular events in 12.9%. RESULTS: Mean follow-up was 39.1 months (range, 25-61). Early and late mortality was 0.99% and 1.0%, respectively. Early reoperation was performed in 2.5%. Early and late major complications were 8.4% and 3.5%. Early most frequent complications were pneumonia and ileus. Intestinal obstruction was diagnosed in 1.5%. Mean BMI decreased from 29.7 to 23.5 kg/m(2), mean fasting glucose from 202.1 to 112.2 mg/dl, and mean postprandial glucose from 263.3 to 130 mg/dl. Triglycerides diminished from a mean of 273.4 to 110.3 mg/dl and cholesterol from a mean of 204.7 to 160.1 mg/dl. Hypertension was resolved in 87.5%. Mean hemoglobin A(1c) (HbA(1c)) decreased from 8.7 to 6.2% after the JII-SG and to 5.9% following the DII-SG. HbA(1c) below 7% was seen in 89.9% of the patients and below 6.5% in 78.3%. Overall, 86.4% of patients were off antidiabetic medications. CONCLUSION: Both JII-SG and DII-SG demonstrated to be safe, effective, and long-lasting alternatives for the treatment of T2DM patients with BMI <35. Beyond glycemic control, other benefits were achieved.
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Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Obesidade/cirurgia , Adulto , Análise de Variância , Anastomose Cirúrgica/métodos , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Duodeno/cirurgia , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Humanos , Íleo/cirurgia , Jejuno/cirurgia , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of this study was to evaluate the effect of the duodenal-jejunal bypass liner (DJBL), a 60-cm, impermeable fluoropolymer liner anchored in the duodenum to create a duodenal-jejunal bypass, on metabolic parameters in obese subjects with type 2 diabetes. METHODS: Twenty-two subjects (mean age, 46.2±10.5 years) with type 2 diabetes and a body mass index between 40 and 60 kg/m(2) (mean body mass index, 44.8±7.4 kg/m(2)) were enrolled in this 52-week, prospective, open-label clinical trial. Endoscopic device implantation was performed with the patient under general anesthesia, and the subjects were examined periodically during the next 52 weeks. Primary end points included changes in fasting blood glucose and insulin levels and changes in hemoglobin A1c (HbA1c). The DJBL was removed endoscopically at the end of the study. RESULTS: Thirteen subjects completed the 52-week study, and the mean duration of the implant period for all subjects was 41.9±3.2 weeks. Reasons for early removal of the device included device migration (n=3), gastrointestinal bleeding (n=1), abdominal pain (n=2), principal investigator request (n=2), and discovery of an unrelated malignancy (n=1). Using last observation carried forward, statistically significant reductions in fasting blood glucose (-30.3±10.2 mg/dL), fasting insulin (-7.3±2.6 µU/mL), and HbA1c (-2.1±0.3%) were observed. At the end of the study, 16 of the 22 subjects had an HbA1c<7% compared with only one of 22 at baseline. Upper abdominal pain (n=11), back pain (n=5), nausea (n=7), and vomiting (n=7) were the most common device-related adverse events. CONCLUSIONS: The DJBL improves glycemic status in obese subjects with diabetes and therefore represents a nonsurgical, reversible alternative to bariatric surgery.
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Cirurgia Bariátrica/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Duodeno/cirurgia , Endoscopia , Jejuno/cirurgia , Obesidade/sangue , Remoção de Dispositivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Seleção de Pacientes , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Laparoscopic ileal interposition associated with a sleeve gastrectomy (LII-SG) is a safe and effective operation for the treatment of type 2 diabetic (T2DM) patients with BMI below 35. The aim of this study was to evaluate insulin sensitivity (IS) and ß-cell function using the euglycemic hyperinsulinemic clamp (EHC) with the intravenous glucose tolerance test (IVGTT). METHODS: This was a prospective study of 24 T2DM patients submitted to a 3-hour EHC-IVGTT before and 1 month after LII-SG. Mean BMI was 29.0, mean age was 54.8 years and mean duration of T2DM was 10.2 years; insulin therapy was used by 62.5% of the patients. RESULTS: Mean BMI decreased from 29.0 to 25.8 (p < 0.001). Mean fasting plasma glucose and mean postprandial glucose were 202 and 251.3 mg/dl and dropped to 127.7 and 131.8 mg/dl (p < 0.001), respectively. Mean preoperative IS was 1.4 mmol·min(-1)·nmol(-1) and increased to 2.2 mmol· min(-1)·nmol(-1) postoperatively (p < 0.001). Mean C-peptide AUC was 488 pmol·nmol(-1) and increased to 777 pmol· nmol(-1) (p = 0.37). The disposition index increased from 9.4 to 36.4 postoperatively (p = 0.01). CONCLUSIONS: According to the clamp technique, II-SG significantly improved IS and ß-cell function as early as 30 days postoperatively in a T2DM population with a BMI of 21.9-33.8.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Gastrectomia , Íleo/cirurgia , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/fisiologia , Adulto , Área Sob a Curva , Cirurgia Bariátrica , Índice de Massa Corporal , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Obesidade/cirurgia , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Redução de PesoRESUMO
The combination of bupropion and naltrexone is one of the most promising new possibilities for the treatment of obesity in an era of increasing prevalence of this disease and decreasing options for its pharmacological management. Although approved by FDA panel members, it was temporally rejected by the FDA afterwards, who demanded more cardiovascular safety data for its commercialization. This monograph will focus on the physiology involved in its mechanisms of action and results of clinical trials.
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Bupropiona/administração & dosagem , Naltrexona/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Bupropiona/farmacologia , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Naltrexona/farmacologiaRESUMO
INTRODUCTION: Bariatric surgery in morbidly obese type 2 diabetic (T2DM) patients is associated with high rates of diabetes remission. We investigated the mechanisms of the anti-diabetic effect of the laparoscopic ileal interposition with sleeve gastrectomy (LII-SG) in normal weight (NW), overweight (OW) and obese (OB) T2DM patients. METHODS: Ninety-four patients (aged 54 ± 8 years) with long-standing (median 10 years), treated diabetes (median HbA(1c) = 8.6%), who were NW (15), OW (64) or OB (15) based on BMI, underwent LII-SG. Insulin sensitivity and parameters of ß-cell function were measured from an Oral Glycaemic Tolerance Test pre- and post-operatively. RESULTS: At a median of 13.4 months post-operatively, weight loss averaged 9.4 ± 1.3, 16.8 ± 0.8 and 23.2 ± 1.7 kg in NW, OW and OB subjects, respectively (p < 0.0001). Insulin sensitivity was fully restored (395 [108] vs 208 [99] ml min⻹ m⻲), fasting insulin secretion rate decreased (68 [52] vs 146 [120] pmol min⻹ m⻲) and total insulin output increased (52 [26] vs 39 [28] nmol m⻲, all p ≤ 0.001). ß-cell glucose sensitivity doubled (37 [33] vs 18 [24] mol min⻹ m⻲ mM⻹, p < 0.0001). The only parameter predicting remission of diabetes was a lower baseline insulin sensitivity (p = 0.005). CONCLUSIONS: LII-SG induced changes on T2DM by mechanisms in part distinct from weight loss, principally involving restoration of insulin sensitivity and improvement of ß-cell function.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Íleo/cirurgia , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/fisiologia , Cirurgia Bariátrica/métodos , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Obesidade/cirurgia , Sobrepeso/sangue , Sobrepeso/fisiopatologia , Sobrepeso/cirurgiaRESUMO
BACKGROUND: This study aims to evaluate the effectiveness of the duodenojejunal bypass liner (DJBL) in the improvement of insulin resistance and reduction of cardiovascular risk among morbidly obese patients with type 2 diabetes mellitus, using the triglyceride/high-density lipoprotein (HDL) cholesterol ratio, percentage of weight loss, and glycemic control. METHODS: We used the TG/HDL ratio with a cutoff value of 3.5 to identify patients with insulin resistance. The value of the initial ratio was compared with the ratio obtained 6 months after implantation to evaluate whether an improvement in insulin resistance occurred. We also evaluated the improvement of glycated hemoglobin levels and the weight loss resulted from the use of the device and correlated that with the improvement of the TG/HDL ratio. RESULTS: All patients implanted with the device presented a statistically significant reduction of the HbA1c levels, with most patients (70.3%) obtaining diabetes control with HbA1c levels lower than 7% at the end of the study. All patients also presented a significant weight reduction, with an average loss of 12.6% of their initial weight. We observed an important improvement in insulin resistance and metabolic syndrome, with a significant reduction of the TG/HDL ratio from 5.75 to 4.36 (p < 0.001) and 42.6% of the patients presenting a TG/HDL ratio lower than 3.5 at the end of the study. CONCLUSIONS: The DJBL, when used for a period of 6 months, is effective in the control of diabetes, weight loss, improvement of insulin resistance, and decrease of cardiovascular risk among morbidly obese patients with type 2 diabetes mellitus.
Assuntos
Cirurgia Bariátrica/instrumentação , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Resistência à Insulina , Obesidade Mórbida/cirurgia , Próteses e Implantes , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Endoscopia Gastrointestinal , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Risco , Resultado do Tratamento , Triglicerídeos/sangue , Redução de Peso , Adulto JovemRESUMO
BACKGROUND: Obesity is related to a higher rate of infections and some types of cancer. Here we analyzed the impact of obesity and weight loss induced by Roux-en-Y gastric bypass (RYGB) on immunological parameters, i.e., cytokine productions and natural killer cell function. METHODS: We analyzed 28 morbidly obese patients before and 6 months after RYGB. Biochemical parameters were analyzed in plasma. The percent of natural killer (NK) cells, their cytotoxicity, and the production of cytokines by peripheral blood mononuclear cells were analyzed. The percent of NK cells was determined by flow cytometry and cytokine production determined by enzyme-linked immunosorbent assay. NK cytotoxicity was determined by the lactate dehydrogenase release assay. RESULTS: The weight loss 6 months following surgery was 35.3 ± 4.5 kg. RYGB also improves biochemical parameters. No significant difference was found in the percent of NK cells after surgery. We found an increase in the production of interferon-γ, interleukin (IL)-12 and IL-18, but not in IL-2, 6 months after RYGB. Cytotoxic activity of NK cells was significantly enhanced 6 months after RYGB [17.1 ± 14.7% before RYGB vs 51.8 ± 11.3% at 6 months after, at 40:1 effector to target cell ratio; p < 0.001]. We observed significant post-surgical improvement in the cytotoxic activity curve in 22 out of 28 patients (78.6%), irrespective of the target to effector cell ratio. CONCLUSIONS: The weight loss induced by RYGB modifies the production of cytokines related with NK cell function and improves its activity.
Assuntos
Citocinas/biossíntese , Células Matadoras Naturais/imunologia , Obesidade Mórbida/imunologia , Obesidade Mórbida/cirurgia , Adulto , Citocinas/imunologia , Feminino , Derivação Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Redução de Peso/imunologiaRESUMO
BACKGROUND: The objective of this study was to evaluate the early results of the laparoscopic interposition of a segment of ileum associated with a sleeve gastrectomy (LII-SG) in order to treat patients with type 2 diabetes mellitus (T2DM) and BMI <35. Data regarding morbidly obese diabetic patients subjected to surgery has consistently been validated. To date, there is scarce information about morbidity and mortality related to the surgical treatment of a "true" typical diabetic population with BMI <35. METHODS: The procedures were performed in 454 patients (322 male, 132 female). Mean age was 53.6 ± 8 years (range = 27-75). Mean BMI was 29.7 ± 3.6 kg/m(2) (range = 19-34.8). All patients had the diagnosis of T2DM for at least 3 years. Insulin therapy was used by 45.6% of patients. Mean duration of T2DM was 10.8 ± 5.9 years (range = 3-35). Mean hemoglobin A(1c) was 8.8 ± 1.9%. Dyslipidemia was observed in 78.4%, hypertension in 64.8%, nephropathy in 28.6%, retinopathy in 32.6%, neuropathy in 34.6%, and coronary heart disease in 13%. RESULTS: There was no conversion to open surgery. All patients were evaluated postoperatively. Mortality was 0.4%. There were 29 major complications (6.4%) in 22 patients (4.8%) and 51 minor complications (11.2%). Reoperations were performed on 8 patients (1.7%). Twenty patients (4.4%) were readmitted to the hospital. Mean postoperative BMI was 25.8 ± 3.5 kg/m(2). Mean fasting plasma glucose decreased from 198 ± 69 to 128 ± 67 mg/dl and mean postprandial plasma glucose decreased from 262 ± 101 to 136 ± 43 mg/dl. CONCLUSIONS: The laparoscopic ileal interposition associated with a sleeve gastrectomy was considered a safe operation with low rates of morbidity and mortality in a diabetic population with BMI < 35. An early control of postprandial glycemia was observed.