Gastric bypass achieves weight loss in the morbidly obese. Preoperative weight loss is used to reduce the enlarged fatty liver that otherwise reduces visibility during surgery. The purpose of gastric bypass is to provide patients with long-term weight loss. The aim of this thesis was to investigate the result of preoperative low calorie diet on liver volume and to evaluate the long-term result of gastric bypass. Paper I showed that four weeks of low calorie diet reduces intrahepatic fat by 40% and facilitates surgery mainly through improved visualisation. Paper II demonstrated that all of the reduction of liver volume occurs during the first two weeks of treatment with low calorie diet.  In paper I liver volume was reduced by 12% and in paper II by 18%. Paper III focused on long-term results and showed that gastric bypass achieves a mean 63% excess body mass index loss in obese patients after 11 years. However, of these 40% undergo abdominoplasty and 2% require additional bariatric surgery. Only 24% adhere to the lifelong recommendation on multivitamins and 72% to Vitamin B12 recommendations. Paper IV evaluated gastric bypass as a revisional procedure after earlier restrictive surgery had failed. Similar weight results as after primary gastric bypass are attained. No patient taking vitamin B12 supplementation was deficient at follow-up, regardless of whether the vitamin was taken as a pill or as intramuscular injections.

<p>Background: Bariatric surgery produces marked weight loss and improvement in comorbid health conditions among individuals with Class II or Class III obesity (Class I = 30.0 &le; BMI &le; 34.9kg/m2; Class II = 35.0 &le; BMI &ge; 39.9kg/m2; Class III = BMI &ge; 40 kg/m2). However, suboptimal weight outcomes occur in a significant minority of patients. Evidence suggests that psychological and behavioral factors might affect weight loss, but most of the literature has focused on preoperative factors, with mixed results. The current study tested the hypothesis that postoperative depressive symptoms, eating behaviors, and lower levels of physical activity would be associated with poorer weight loss outcomes. Method: Preoperative data were obtained from an extant clinical database, and postoperative data were collected via a mail or online questionnaire in a sample of 141 female Roux-en-y gastric bypass (RYGB) patients at an average of 16.80 (SD=2.20) months post-surgery. Self-report measures assessed cognitive-affective and somatic symptoms of depression; binge eating, grazing, night eating, distress about overeating or loss of control over eating; and physical activity. Results: Weight outcome measures were defined as percentage of excess BMI loss (%EBMIL) and successful weight loss (&ge; 50% EBMIL). Higher distress was associated with poorer %EBMIL, and higher level of physical activity was associated with greater %EBMIL. Decreased cognitive-affective symptoms and increased somatic symptoms of depression were associated with a higher probability of successful weight loss. Increased somatic complaints predicted greater %EBMIL unless those symptoms were associated with higher sedentary behavior. Conclusions: Consistent with hypotheses, preoperative depressive symptoms and binge eating disorder did not predict weight loss. Aspects of all three postoperative domains were associated with weight outcomes. Future research should explore the relations among these psychological and behavioral factors and weight loss over a longer follow-up period.</p> / Dissertation

Τα επίπεδα της γκρελίνης και του PYY μετά από χειρουργείο χολοπαγκρεατικής εκτροπής και Roux-en-Y γαστρικού bypass και μετά από χειρουργείο κολεκτομής: προοπτική συγκριτική μελέτη Οι ορμόνες του γαστρεντερικού γκρελίνη και PYY έχει αποδειχθεί ότι παίζουν κάποιο ρόλο στη ρύθμιση του μεταβολισμού και της όρεξης. Μελετάμε την επίδραση του χειρουργείου της χολοπαγκρεατικής εκτροπής και RYGBP (BPD-RYGBP) στα κυκλοφορούντα επίπεδα της γκρελίνης και του PYY άμεσα μετεγχειρητικά και τα συγκρίνουμε με την αντίστοιχη επίδραση μιας άλλης χειρουργικής επέμβασης της ίδιας βαρύτητας, την κολεκτομή. Μέθοδος. Μελετάμε τα επίπεδα νηστείας της γκρελίνης και του PYY σε 20 παχύσαρκους ασθενείς (super-obese) που υποβλήθηκαν σε BPDRYGBP και σε 13 ασθενείς που υποβλήθηκαν σε κολεκτομή για καρκίνο παχέος εντέρου. Οι μετρήσεις έγιναν προεγχειρητικά, και τις μετεγχειρητικές ημέρες 1,3,7,30 και 90 και στις δύο ομάδες, καθώς και στον 1 χρόνο στην ομάδα των παχυσάρκων. Αποτελέσματα. Προεγχειρητικά, τα επίπεδα και της γκρελίνης και του PYY ήταν χαμηλότερα στην ομάδα των παχυσάρκων. Μια προσωρινή μείωση των τιμών της γκρελίνης παρατηρήθηκε και στις δύο ομάδες άμεσα μετεγχειρητικά με σταδιακή επάνοδο στα προεγχειρητικά επίπεδα έως τον 3ο μήνα. Επιπλέον τα επίπεδα της γκρελίνης αυξήθηκαν 40%, σε σύγκριση με τα προεγχειρητικά, στην ομάδα των παχυσάρκων στον 1ο χρόνο παρακολούθησης. Τα επίπεδα του PYY στην ομάδα των κολεκτομών μειώθηκαν τις πρώτες 3 μετεγχειρητικές ημέρες και έπειτα επέστρεψαν στα προεγχειρητικά. Σε αντίθεση, τα επίπεδα του PYY στην ομάδα των παχυσάρκων δεν άλλαξαν άμεσα μετεγχειρητικά αλλά αυξήθηκαν σε επίπεδα 50% υψηλότερα στον 3ο μήνα και 170% υψηλότερα στον 1ο χρόνο, σε σύγκριση με τα προεγχειρητικά. Συμπεράσματα. Η μεγάλη μετεγχειρητική αύξηση των επιπέδων της ανορεξιογόνου ορμόνης PYY μετά από BPD-RYGBP μπορεί να παίζει ρόλο στην μειωμένη όρεξη που παρατηρείται μετά από αυτό τον τύπο βαριατρικής επέμβασης. Οι αλλαγές της γκρελίνης μετεγχειρητικά κάνουν τη συμμετοχή της ορμόνης αυτής στη μείωση της όρεξης λιγότερο πιθανή. / Ghrelin and Peptide YY levels anfter a variant of biliopancreatic diversion with Roux-en-Y gastric bypass versus after colectomy: A prospective comparative study Background. The gastrointestinal peptide hormones ghrelin and PYY, have been shown to play a role in the regulation of metabolism and apetite. We investigate the effect of the biliopancreatic diversion with Roux-en-Y gastric bypass (BPD-RYGBP) procedure on the circulating levels of ghrelin and PYY during the first 3 months postoperatively as compared to the effects of colectomy, an abdominal operation of similar severity. Methods. We determined the fasting plasma levels of ghrelin and PYY in 20 morbidly super obese patients that underwent BPD-RYGBP and in 13 subjects that underwent a colectomy because of large bowel cancer. Fasting plasma ghrelin and PYY levels were measured preoperatively and during the postoperative period on days 1,3,7,30 and 90 in all patients of both groups and at the 1 year for the patients who had attained 1-year follow up. Results. Preoperatively, both plasma ghrelin and PYY levels were lower in the BPD-RYGBP group of patients. A temporary decrease in plasma ghrelin levels was observed in both groups of patients during the immediate postoperative period with a gradual return to preoperative levels by the third month. In addition, ghrelin concentrations increased at one year to levels 40% higher than those in baseline, in ten of the BPD-RYGBP patients who had completed the one-year follow up (p=0.004). Plasma PYY levels in the colectomy group decreased the first three postoperative days and then returned to baseline. In contrast, PYY levels in the BPD-RYGBP group did not change during the early postopera¬tive period but increased to levels 50% higher at 3 months (p<0.001) and 170% higher at one year (p<0.001) than the baseline. Conclusions. The great postoperative increase of the levels of the anorexigenic peptide PYY following BPD-RYGBP may contribute to the reduced appetite observed after this type of bariatric surgery. The changes in ghrelin levels postoperatively make its contribution to the appetite suppression less likely.

BACKGROUND AND AIMS: Obesity is associated with vascular endothelial dysfunction, which predisposes obese persons to cardiovascular disease. Fat loss in obese persons can lead to metabolic improvements that promote improved cardiovascular health and decrease risk of stroke or myocardial infarction. The objective of this study was to assess the potential of weight loss achieved by bariatric surgery to improve endothelial function. METHODS: Patients scheduled to undergo bariatric surgery were prospectively followed. Biochemical analyses and vascular function testing were performed preoperatively and again at 1, 3, 6, and 12 months postoperatively. FMD and NMD were measured to assess macrovascular endothelial function and ∆ hyperemic flow was measured to assess microvascular endothelial function. RESULTS: Patients (n = 375) ages 41.76 ± 12.35 years, with baseline BMI of 45.64 ± 8.36, experienced a weight reduction of 82.07 ± 33.98 lbs the year following surgery. FMD % increased by 1.28 ± 5.49, NMD % by 4.26 ± 6.23, and ∆ hyperemic flow % by 262.1 ± 519.97. All vascular function variables demonstrated a significant increase over time (p < 0.05) with ∆ hyperemic flow % experiencing the most significant change (p < 0.0001). No difference was found in improvement in vascular function between high (>13 µIU/ml) and low (≤13 µIU/ml) baseline plasma insulin groups (p values all > 0.05). CONCLUSIONS: Bariatric surgery was associated with an improvement in macrovascular and microvascular endothelial function. Further analyses is needed to determine which clinical parameters are optimal predictors of improvements in vascular endothelial function after bariatric surgery.

BACKGROUND: Bariatric surgery is an effective weight loss treatment modality for people with morbid obesity, however, there may be a negative impact on postoperative bone health. This review summarizes changes of different bone mineral density dual-energy x-ray absorptiometry measurements, with specific attention to the laparoscopic sleeve gastrectomy and the roux-en-y gastric bypass. METHODS: PubMed and the Cochrane Library searches yielded 156 articles published before November 2017. The articles were evaluated based on the following inclusion criteria: focus on laparoscopic sleeve gastrectomy or roux-en-y gastric bypass and bone health, written in English, full-length article, studied participants for one-to-two years, and included statistical measurements. RESULTS: Of the 156 studies that were initially screened, 16 full-length articles were included in the final analysis. The articles described a lower loss of bone density at the lumbar spine, femoral neck, forearm, and total hip after laparoscopic sleeve gastrectomy when compared to roux-en-y gastric bypass, however, these studies lack statistical power due to the small sample sizes of less than 10 participants. CONCLUSION: The number of bariatric surgeries continues to increase worldwide, however, the literature provides limited studies that evaluate the effects of bariatric surgery on bone health, more than two-years postoperative. Further study is necessary to determine the mechanisms of bone loss after bariatric surgery, with great attention to differences in bone health between sexes.

Resumo: A obesidade é uma doença crônica e de caráter epidemiológico, repercutindo de maneira importante na saúde do indivíduo e na sociedade. Atualmente, a cirurgia bariátrica, em especial a Bypass gástrico em Y de Roux (BGYR), vem se popularizando como uma forma de tratamento dessa condição, garantindo perda do excesso de peso superior às terapias convencionais, com manutenção em longo prazo. Contudo, observa-se que, por se tratar de uma cirurgia com componentes restritivos e disabsortivos, o BGYR, pode levar a redução na absorção e ingestão de nutrientes essenciais a homeostase corporal e em especial, a homeostase óssea. Com isso, podem ocorrer alterações no metabolismo ósseo e, consequentemente na estrutura óssea. Os objetivos do presente estudo foram avaliar o efeito da referida cirurgia sobre a ingestão de nutrientes e parâmetros relacionados à remodelação óssea de pacientes obesas antes e após três e seis meses do procedimento, averiguando se existe associação entre a ingestão alimentar e a evolução destes parâmetros. Neste estudo, prospectivo e observacional, foram estudadas 25 mulheres, submetidas ao procedimento de BGYR, no período de maio de 2009 a maio de 2010, no Hospital das Clínicas da Faculdade de Medicina de Botucatu, Unesp. Para avaliação da ingestão energética e de cálcio, magnésio, fósforo, vitamina D e macronutrientes, foi aplicado um registro alimentar de 72 horas, nos três momentos de avaliação, calculando-se as variáveis por meio do software de nutrição Dietpro 5.i Profissional. Os dados comportamentais foram coletados por meio de um protocolo de avaliação, desenvolvido pela equipe, considerando-se uso de tabaco, álcool e prática de atividade física. Foi realizada avaliação antropométrica, aferindo-se circunferências da cintura, abdominal e quadril, além do peso corporal e seus componentes, analisados pelo método... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Obesity is a chronic disease and an epidemic, resulting in a significant way in the health of the individual and society. Nowadays, bariatric surgery in special gastric bypass Roux-Y (BGYR) has become popular as a treatment, ensuring loss of overweight superior to conventional therapies, with long term maintenance. However, it was observed that, because it is a surgery with disabsorptive and restrictive components, the RYGB may lead to reduced absorption and intake of essential nutrients, necessary for the body homeostasis and, specially, bone homeostasis. Thus, changes in bone metabolism may occur and, consequently, changes in bone structure. The objectives of the present study were to evaluate the effect of the surgery on nutrients intake and on parameters related to bone remodeling in obese patients, before and after three and six months of the procedure, by examining the association between food intake and evolution of these parameters. A prospective and observational study evaluated 25 women who underwent the RYGB procedure, from May 2009 to May 2010, at the Hospital of the Medical School of Botucatu, UNESP. For evaluation of energy, calcium, magnesium, phosphorus, vitamin D and macronutrients consumption, a 3 days food record was carried out before and after surgery, and calculated on DietPro 5.i Professional nutrition software. Behavioral data were collected by an assessment protocol, developed by the team, considering use of tobacco, alcohol and physical activity. Anthropometric assessment was performed by measuring waist circumference, waist, hip and body weight, and components of body weight were analyzed by bioelectrical impedance method. Laboratory tests of bone metabolism were also conducted, such as: calcium (urine and serum), serum magnesium and phosphorus, total alkaline phosphatase and bone specific alkaline phosphate (BSAP), parathyroid hormone (PTH), carboxy-te... (Complete abstract click electronic access below) / Orientador: Gláucia M. F. Mazeto / Coorientador: Adriana Mendes / Coorientador: Celso Vieira Leite / Banca: Célia Regina Nogueira / Banca: José Gilberto Henriques Vieira / Mestre

A prevalência mundial da obesidade tem aumentado dramaticamente nos últimos anos. Classificada como doença crônica, a obesidade está associada a uma série de doenças, como hipertensão arterial sistêmica, diabetes mellitus tipo 2 ehipercolesterolemia, aumentando a necessidade de uso de medicamentos. Esta situação contribui para a redução da qualidade e expectativa de vida dos indivíduos. A perda de peso significativa por pacientes com obesidade mórbida pode ser obtida através da realização da cirurgia bariátrica que pode exigir ajustes na farmacoterapia em função da redução das comorbidades e das alterações fisiológicas provocadas pela cirurgia. Objetivo: Analisar o impacto da cirurgia bariátrica sobre o perfil de utilização dos medicamentos, enfocando principalmente as classes terapêuticas, o número de medicamentos e doses administradas antes e após a cirurgia. Métodos: Foi realizado um estudo longitudinal do tipo antes e depois. Utilizando uma amostragem por conveniência foram entrevistados consecutivamente 69 pacientes no pré-cirúrgico imediato e seis meses após a realização do procedimento cirúrgico entre 2008 e 2011. Nas entrevistas foram avaliados a presença de comorbidades e o uso de medicamentos com e sem prescrição médica Resultados: Antes da cirurgia 85,5% dos pacientes apresentaram comorbidades associadas à obesidade, sendo as principais: hipertensão, diabetes e hipercolesterolemia. 84,1% dos pacientes estavam em uso de medicamento sob prescrição médica no período pré-cirúrgico e a média de medicamentos utilizados por paciente foi de 4,8. Após a realização da cirurgia, observamos uma diminuição acentuada para as classes dos antidiabéticos (84%), antilipêmicos (77%) e anti-hipertensivos (49,5%), e a média de medicamentos por paciente foi de 4,4. Por outro lado observou-se um aumento importante na utilização de multivitamínicos e medicamentos para desordens do trato gastrointestinal (TGI). A maioria dos medicamentos que continuaram sendo prescritos após a cirurgia teve sua dose reduzida. Conclusão: A cirurgia bariátrica propiciou a redução da dose e da utilização de medicamentos para a maioria das classes terapêuticas. No entanto, pode ser observado um aumento na utilização de medicamentos para tratar distúrbios associados à realização da cirurgia. / The worldwide prevalence of obesity has increased dramatically in the last years. Classified as a chronic disease, obesity is associated with a number of diseases, such as hypertension, type 2 diabetes mellitus and hypercholesterolemia, increasing the need for drug use. This situation reduces the quality and life expectancy of individuals. The significant weight loss for morbidly obese patients can be obtained by bariatric surgery that may require adjustments in pharmacotherapy due to the reduction of comorbidities and physiological changes caused by surgery. Objective: Analyze the impact of bariatric surgery on the drug use profile, mainly focusing on the therapeutic classes, the number of drugs and doses administered before and after surgery. Methods: We conducted a longitudinal study of type before and after. Using a convenience sampling were interviewed consecutively 69 patients before surgery immediately and six months after the surgical procedure between 2008 and 2011. In the interviews were evaluated the presence of comorbidities and the use of prescription and non-prescription Results: Before surgery 85.5% of patients had comorbidities associated with obesity, the main ones being: hypertension, diabetes and hypercholesterolemia. 84.1% of patients were on prescription drug use in the preoperative period and the average number of drugs used per patient was 4.8. After the surgery, we observed a marked decrease for the classes of antidiabetic (84%), antilipemic (77%) and antihypertensive (49.5%), and the average number of drugs used per patient was 4,4. Moreover we observed a significant increase in the use of multivitamin and medicaments for disorders of the gastrointestinal tract (GIT). Most drugs that continued to be prescribed after surgery was reduced dose. Conclusion: Bariatric surgery led to dose reduction and the use of medications for most therapeutic classes. However, an increase can be observed in the use of drugs to treat disorders associated with surgery.

A prevalência mundial da obesidade tem aumentado dramaticamente nos últimos anos. Classificada como doença crônica, a obesidade está associada a uma série de doenças, como hipertensão arterial sistêmica, diabetes mellitus tipo 2 ehipercolesterolemia, aumentando a necessidade de uso de medicamentos. Esta situação contribui para a redução da qualidade e expectativa de vida dos indivíduos. A perda de peso significativa por pacientes com obesidade mórbida pode ser obtida através da realização da cirurgia bariátrica que pode exigir ajustes na farmacoterapia em função da redução das comorbidades e das alterações fisiológicas provocadas pela cirurgia. Objetivo: Analisar o impacto da cirurgia bariátrica sobre o perfil de utilização dos medicamentos, enfocando principalmente as classes terapêuticas, o número de medicamentos e doses administradas antes e após a cirurgia. Métodos: Foi realizado um estudo longitudinal do tipo antes e depois. Utilizando uma amostragem por conveniência foram entrevistados consecutivamente 69 pacientes no pré-cirúrgico imediato e seis meses após a realização do procedimento cirúrgico entre 2008 e 2011. Nas entrevistas foram avaliados a presença de comorbidades e o uso de medicamentos com e sem prescrição médica Resultados: Antes da cirurgia 85,5% dos pacientes apresentaram comorbidades associadas à obesidade, sendo as principais: hipertensão, diabetes e hipercolesterolemia. 84,1% dos pacientes estavam em uso de medicamento sob prescrição médica no período pré-cirúrgico e a média de medicamentos utilizados por paciente foi de 4,8. Após a realização da cirurgia, observamos uma diminuição acentuada para as classes dos antidiabéticos (84%), antilipêmicos (77%) e anti-hipertensivos (49,5%), e a média de medicamentos por paciente foi de 4,4. Por outro lado observou-se um aumento importante na utilização de multivitamínicos e medicamentos para desordens do trato gastrointestinal (TGI). A maioria dos medicamentos que continuaram sendo prescritos após a cirurgia teve sua dose reduzida. Conclusão: A cirurgia bariátrica propiciou a redução da dose e da utilização de medicamentos para a maioria das classes terapêuticas. No entanto, pode ser observado um aumento na utilização de medicamentos para tratar distúrbios associados à realização da cirurgia. / The worldwide prevalence of obesity has increased dramatically in the last years. Classified as a chronic disease, obesity is associated with a number of diseases, such as hypertension, type 2 diabetes mellitus and hypercholesterolemia, increasing the need for drug use. This situation reduces the quality and life expectancy of individuals. The significant weight loss for morbidly obese patients can be obtained by bariatric surgery that may require adjustments in pharmacotherapy due to the reduction of comorbidities and physiological changes caused by surgery. Objective: Analyze the impact of bariatric surgery on the drug use profile, mainly focusing on the therapeutic classes, the number of drugs and doses administered before and after surgery. Methods: We conducted a longitudinal study of type before and after. Using a convenience sampling were interviewed consecutively 69 patients before surgery immediately and six months after the surgical procedure between 2008 and 2011. In the interviews were evaluated the presence of comorbidities and the use of prescription and non-prescription Results: Before surgery 85.5% of patients had comorbidities associated with obesity, the main ones being: hypertension, diabetes and hypercholesterolemia. 84.1% of patients were on prescription drug use in the preoperative period and the average number of drugs used per patient was 4.8. After the surgery, we observed a marked decrease for the classes of antidiabetic (84%), antilipemic (77%) and antihypertensive (49.5%), and the average number of drugs used per patient was 4,4. Moreover we observed a significant increase in the use of multivitamin and medicaments for disorders of the gastrointestinal tract (GIT). Most drugs that continued to be prescribed after surgery was reduced dose. Conclusion: Bariatric surgery led to dose reduction and the use of medications for most therapeutic classes. However, an increase can be observed in the use of drugs to treat disorders associated with surgery.

Introdução: Pacientes com Índice de Massa Corporal (IMC) maior ou igual 50kg/m2 podem atingir perda de peso adequada após derivação gástrica em Y de Roux de alça longa. No entanto, esses pacientes podem necessitar de alças intestinais mais longas para controle ou melhora de doenças associadas à obesidade, como o diabetes mellitus do tipo 2. Casuística e métodos: Estudo prospectivo de 100 pacientes com Índice de Massa Corporal (IMC) maior ou igual 50kg/m2 divididos em 2 grupos similares quanto ao sexo, idade e tipo de doença associada. Todos os pacientes foram submetidos à derivação gástrica em Y de Roux por laparoscopia. No grupo 1, o comprimento da alça biliar foi de 50 cm e o da alça alimentar, de 150 cm. No grupo 2, o comprimento da alça biliar foi de 100 cm e o da alça alimentar, de 250 cm. Resultados: O seguimento foi de 48 meses. O diabetes mellitus do tipo 2 foi controlado em 58% dos pacientes do grupo 1 e em 93% dos pacientes do grupo 2 no pós-operatório (p<0,05). A perda do excesso de peso foi mais rápida no grupo 2, mas semelhante nos 2 grupos estudados aos 48 meses, sem diferença estatística. Conclusões: Pacientes com Índice de Massa Corporal (IMC) maior ou igual 50kg/m2 submetidos à derivação gástrica em Y de Roux com alças biliar e alimentar mais longas apresentaram maior controle de diabetes mellitus do tipo 2 do que pacientes com alças mais curtas. / Background: Patients With Body Mass Index (BMI) > or = 50kg/m2 may achieve adequate weight loss with long limb RYGB. These patients, however, might need longer intestinal limbs to control co-morbidities such as type 2 diabetes. Methods: A prospective study of 100 super-obese patients who were divided in 2 similar groups regarding sex, age, and number of co-morbidities. All were submitted to laparoscopic RYGB. In group 1, length of biliary limb was 50 cm and length of Roux limb was 150 cm. In group 2, length of biliary limb was 100 cm and of Roux limb was 250 cm. Results: Follow-up was 48 months. Diabetes was controlled in 58% of group 1 patients and in 93% of group 2 patients (p<0.05). Excess weight loss was faster in group 2, but was similar in both groups at 48 months, with no statistical difference. Conclusions: Super-obese patients with longer biliary and Roux limbs achieved greater type 2 diabetes control.

Orientador: Sarah Monte Alegre / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T11:18:08Z (GMT). No. of bitstreams: 1 Marin_DanielaMiguel_D.pdf: 9757460 bytes, checksum: 86661914830aec4c7fce8aad1a6f4f35 (MD5) Previous issue date: 2007 / Resumo: A obesidade é caracterizada pela presença de resistência à insulina e hiperinsulinemia e constitui em fator de risco para outras doenças, tais como hipertensão arterial, diabetes mellitus, hiperlipidemia (Ashley 1974; Mokdad 2003). Na obesidade, a resistência à insulina induz uma resposta secretória aumentada para um determinado estímulo tanto em condição basal de jejum como após sobrecarga de glicose. A progressão da tolerância normal à glicose ao Diabetes Mellitus tipo 2 em sujeitos eutróficos e com obesidade, é caracterizada por reduções na função da célula ß e diminuição na sensibilidade à insulina e ambas desempenham importante papel fisiopatológico (Unwin et al 2002; Buchana et al 2002; Ferrannini et al 2004; Kitabchi et al 2005). A perda de peso parece melhorar a sensibilidade à insulina, o controle glicêmico (UKPDS 1990; Sjöström 1997; Dixon 2002) e retardar a progressão da intolerância à glicose ao diabetes mellitus (DPP, 2002). Após bypass gástrico essas alterações têm sido demonstradas (Pereira 2003b; Korner 2005, Shah 2006), porém não são bem conhecidas quais mudanças ocorrem na função da célula ß e na relação entre secreção de insulina e resistência à insulina após o emagrecimento maciço induzido por bypass gástrico. Este estudo tem como objetivo avaliar a contribuição da resistência à insulina e da disfunção da célula ß sobre a tolerância a glicose, avaliar a adaptação da secreção de insulina pelo grau de resistência à insulina e avaliar o efeito da perda de peso induzida por bypass gástrico sobre os parâmetros de secreção de insulina, resistência à insulina e a adaptação da secreção de insulina à resistência à insulina. Trinta e dois voluntários com obesidade grau III (15 NT, 11 IT e 6 DM) e 10 controles (CT) foram submetidos a 3 estudos metabólicos: clamp euglicêmico hiperinsulinemico (3h a 240pmol de insulina/min.m-2) com calorimetria indireta, teste intravenoso e teste oral de tolerância à glicose. A sensibilidade à insulina (M) foi calculada a partir da taxa de infusão de glicose durante o clamp. As taxas de secreção total (T-ISR) e de jejum (f-ISR) foram avaliadas pela deconvolução do peptídeo C e a sensibilidade da célula ß à glicose (ß-SG) foi calculada como a inclinação da curva dose resposta de secreção de insulina pela concentração de glicose. O índice adaptation foi calculado como a taxa de secreção de insulina total e de 1ª fase multiplicada pelo M value. 14 voluntários (11 NT e 3 IT) foram reavaliados após a estabilização da perda de peso (~18 meses) induzida por bypass gástrico. Os voluntários obesos eram resistentes à insulina para o consumo total de glicose assim como para o consumo oxidativo e não oxidativo de glicose. A fase rápida de secreção de insulina (RAI: 0-10 min-TETG) foi maior nos obesos normotolerantes comparado aos intolerantes, diabéticos e ao grupo controle (CT 5378±590; OB-NT 9363±895; OB-IT 6544±558 e OB-DM 3893±622 pmol.min-1.m-2x10min), A T-ISR esteve aumentada em todos os subgrupos de obesos (CT 20,2±1,9; OB-NT 39,2±3,6; OB-IT 39,2±2,5 e OB-DM 37,1±4,5 nmol.min-1.m-2x60min) enquanto a sensibilidade da célula ß à glicose e o índice adaptation foram menores nos intolerantes e diabéticos mas não nos obesos normotolerantes quando comparado aos controles (OB-DM -4±3; OB-IT 31±4; OB-NT 56±6 e CT 43±6 pmol.min-1.m-2.mM-1). Após a perda de peso, os voluntários ainda permaneceram na faixa de obesidade (IMC 30,2±1,2kg.m-2), porém a secreção basal de insulina (f-ISR de 148±12 para 83±12 pmol.min-1.m-2, p<0,05) e a sensibilidade à insulina (M de 30±4 para 50±5µmol.kg-1.min-1, p<0,05) foram normalizados. Houve diminuição da secreção total de insulina e aumento da sensibilidade da célula ß à glicose a valores maiores daqueles observados no grupo controle (de 43±7 para 75±10 pmol.min-1.m-2.mM-1). O índice adaptation aumentou a valores maiores que os observados no grupo controle. Em conclusão, este estudo nos permitiu confirmar que mesmo em pacientes portadores de obesidade grave, a intolerância à glicose se manifesta quando a célula ß não consegue manter uma hipersecreção capaz de compensar a importante resistência à insulina, entre outros fatores, por reduzida sensibilidade à glicose. A resistência à insulina é dependente do grau de obesidade e de menores concentrações de adiponectina. O emagrecimento induzido por bypass gástrico em pessoas não diabéticas é capaz de restaurar a sensibilidade à insulina e a sensibilidade à glicose, melhorando o metabolismo dos carboidratos. A extensão deste estudo a pacientes diabéticos emagrecidos pos bypass gástrico é importante para melhor compreender os mecanismos envolvidos / Abstract: The objectives are to evaluate the contribution of insulin resistance and impaired ß-cell function to glucose tolerance in severely obese subjects and the effect of massive weight loss by Roux-en-Y Gastric bypass, RGB-Y, on the adaptation of insulin secretion to insulin resistance (IR). Euglycemic hyperinsulinemic clamp (3h at 240pmol/min.m-2) with indirect calorimetry, IV glucose tolerance test and an OGTT were performed in 32 severe obese subjects (17NGT, 11IGT and 6type 2 diabetic ¿ OB-T2D) and in 10 controls. Insulin sensitivity, Mvalue, was calculated from the glucose infusion rate of the clamp. Total (T-ISR) and fasting insulin secretion rate (f-ISR) were evaluated by C-peptide deconvolution and ß-cell glucose sensitivity (ß-GS) as dose-response curve ISR-to-glucose. Disposition index was calculated as ISRxMvalue. 14 patients (11OB-NGT and 3OB-IGT) were re-evaluated post-surgery after weight stabilization (~18 months). Obese subjects were insulin resistant for oxidative, nonoxidative and whole body glucose disposal (OB-T2D, OB-IGT and OB-NGT were ~30%, 60% and 43% of CT). The acute insulin response (AIR: 0-10min-IVGTT) was higher in OB-NGT than in CT and in other obese groups (CT 5378±590; OB-NGT 9363±895; OB-IGT 6544±558 and OB-T2D 3893±622 pmol.min-1.m-2x10min), T-ISR was elevated in all obese groups (CT 20.2±1.9; OB-NGT 39.2±3.6; OB-IGT 39.2±2.5 and OB-T2D 37.1±4.5 nmol.min-1.m-2x60min) while ß-GS was decreased in OB-IGT and -T2DM but not in -NGT as compared to CT (OB-T2D -4±3; OB-IGT 31±4; OB-NGT 56±6 and CT 43±6 pmol.min-1.m-2.mM-1). The disposition index was reduced in OB-IGT and -T2DM but not in -NGT. After weight loss (BMI 30.2±1.2kg.m-2), f-ISR (from 148±12 to 83±12 pmol.min-1.m-2, p<0.05) and insulin sensitivity (from 30±4 to 50±5µmol.kg-1.min-1, p<0.05) changed to normal values. The time-course evidenced a significant decrease in T-ISR, and an unchanged AIR. ß-GS increased to levels higher than CT (from 43±7 to 75±10 pmol.min-1.m-2.mM-1). The disposition index, similar to the CT group, after weight loss increased to values higher than in CT. T2D and IGT severe obese subjects show a progressive deterioration of glucose homeostasis, despite increased insulin secretion. This can be explained as an impairment of ß-cell function for the prevailing IR. RGB-Y weight loss normalized IR and improved ß-cell function in IGT and NGT obese to levels higher than in lean CT / Doutorado / Ciencias Basicas / Doutor em Clínica Médica