Orientadores: Bruno Geloneze Neto, José Carlos Pareja / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T19:08:38Z (GMT). No. of bitstreams: 1 Vasques_AnaCarolinaJunqueira_D.pdf: 3885114 bytes, checksum: 5657b34693061e6340e284a0a3940e64 (MD5) Previous issue date: 2013 / Resumo: Objetivo: avaliar o efeito da cirurgia de derivação biliopancreática (DBP) na função da célula-beta de mulheres obesas grau I e II portadoras de diabetes mellitus tipo 2 (DM2), utilizando estímulos com glicose oral e intravenosa. Material e métodos: foram avaliadas 68 mulheres na menacme que compuseram três grupos: Controle magro - CMagro (n = 19, IMC = 23,0 ± 2,2 kg/m²), Controle obeso - CObeso: 18 mulheres obesas (IMC = 35,0 ± 4,8 kg/m²), ambos normotolerante à glicose; e Obeso com DM2 - ObesoDM2 (n = 31; IMC: 36,3 ± 3,7 kg/m²). No grupo ObesoDM2, 64% das mulheres foram submetidas à cirurgia de DBP (n = 20, IMC: 36,5 ± 3,7 kg/m²). Os 68 pacientes passaram por todas as avaliações uma única vez. Os pacientes submetidos à DBP foram reavaliados um mês após a cirurgia. A avaliação da célula-beta foi realizada por testes dinâmicos com estímulo oral (teste de tolerância à glicose oral) e intravenoso (clamp hiperglicêmico). Foram dosados glicose, insulina e peptídeo-C plasmáticos. A aplicação das técnicas de modelagem matemática aos dados possibilitou avaliar as secreções de insulina basal, dinâmica e estática (estímulo oral); a primeira e a segunda fase de secreção de insulina (estímulo intravenoso); a secreção de insulina total; a sensibilidade à insulina (SI), a extração hepática de insulina (EH) e o tempo de atraso ou tempo de atraso para a célula-beta recrutar novos grânulos de insulina para compor o reservatório de grânulos prontamente liberáveis em resposta a determinada glicemia. Resultados: após a DBP houve melhora substancial na SI no TTOG e no teste de clamp, com o grupo cirúrgico alcançando níveis semelhantes aos do grupo CMagro e mais elevados que do grupo CObeso (p < 0,05). A EH de insulina apresentou aumento significante após a DBP, com o grupo cirúrgico mantendo-se semelhante ao CMagro e com níveis aumentados em relação ao CObeso (p < 0,05). A secreção de insulina basal do grupo cirúrgico alcançou níveis de normalidade, assemelhando-se ao CMagro. Houve melhora da função da célula-beta estimulada (p < 0,05), independente da via de acesso utilizada para estimular a célula-beta com glicose (oral e intravenosa). O tempo de atraso não apresentou modificação após a DBP. Conclusão: Ocorreram diversas adaptações fisiológicas positivas após a DBP. Estas adaptações estão relacionadas à restauração na SI, à melhora na EH de insulina e à melhora nas diversas etapas do processo de síntese e secreção de insulina, explicando a melhora aguda no nível de tolerância à glicose e no controle glicêmico desses indivíduos. A não melhora no tempo de atraso evidencia as características do DM2 como doença crônica, progressiva e irreversível, uma vez que o tratamento cirúrgico contribui para a remissão e não resolução da doença. A compreensão dos mecanismos de mudança no metabolismo após a DBP ajudará a definir o papel do intestino na fisiopatologia do DM2, contribuindo para o desenvolvimento de novas abordagens clínicas e cirúrgicas para o tratamento da doença / Abstract: Objective: to assess the effect of biliopancreatic diversion surgery (BPD) in beta-cell function of obese grade I and II women with type 2 diabetes mellitus (T2DM), using an oral and an intravenous stimuli with glucose. Research Design and Methods: sixty eight premenopausal women were assessed and divided into three groups: lean control - LeanC (n = 19; BMI: 23.0 ± 2.2 kg/m²), obese control - ObeseC (n = 18; BMI: 35.0 ± 4.8kg/m²), both with normal glucose tolerance; and obese with type 2 diabetes - ObeseT2DM (n = 31; BMI: 36.3 ± 3.7 kg/m²). In ObeseDM2 group, 64% of women underwent BPD (n = 20, BMI: 36.5 ± 3.7 kg/m²). The 68 volunteers underwent all assessments once. The volunteers those underwent BPD were reassessed one month after surgery. The assessment of beta-cell function was performed by dynamic tests with an oral (oral glucose tolerance test) and an intravenous stimulation test (hyperglycemic clamp). Serum glucose, insulin and C-peptide were determined. The application of mathematical modeling techniques to data allowed to evaluate basal, dynamic and static (oral stimulus) insulin secretion; the first and second phase of insulin secretion (intravenous stimulus); the total insulin secretion; the insulin sensitivity (IS); the hepatic extraction of insulin (EH) and the delay time for the beta-cell to recruit new insulin granules to form the pool of readily releasable granules in response to a given plasma glucose. Results: after BPD, there was a dramatic improvement on IS during the OGTT and during the clamp test, with the surgical group reaching normalized levels compared to those observed in LeanC group and higher levels than ObeseC group (p < 0.05). The EH of insulin showed significant improvement after BPD, with the surgical group reaching similar levels to LeanC and with increased levels in comparison to ObeseC (p < 0.05). The basal insulin secretion achieved normalized levels, with the surgical group resembling the LeanC group. There was improvement in stimulated beta-cell function (p < 0.05), independent of the route of glucose administration (oral and intravenous). The delay time presented no improvement after BPD. Conclusion: several positive physiological adaptations occurred after BPD surgery. These adaptations are related to restoration of the IS, improvement in EH of insulin and normalization in beta-cell function at the various stages of the synthesis secretion process of insulin, explaining the improvement on glucose tolerance and on the glycemic control. The lack of improvement on the delay time highlights the characteristics of T2DM as a chronic, progressive and irreversible disease, once the surgical treatment contributes to the remission and not for the resolution of the disease. Understanding the mechanisms of the change in metabolism after BPD should help define the role of the gut in the physiopathology of T2DM, and help to develop new clinical and surgical approaches to treat the disease / Doutorado / Clinica Medica / Doutora em Clínica Médica

Obesity is the fifth leading cause of global deaths. The efficacy and safety of obesity treatment is still controversial. The objective of the thesis is to evaluate the efficacy and safety of bariatric surgery, through a systematic review of the current evidence and meta- analysis of important outcomes. Nineteen (19) randomized controlled trials (RCTs) with 1346 participants were included. Bariatric surgery resulted in greater weight loss when compared to non-surgical treatment. Weight loss was also associated with resolution and/or improvement of obesity related comorbidites such as diabetes, hypertension, hyperlipidemia, and sleep apnea. Weight loss and safety varied across the surgical procedures. Biliopancreatic diversion/duodenal switch had the greatest weight loss, followed by sleeve gastrectomy and Roux-en-Y gastric bypass, purely restrictive procedures such as vertical banded gastroplasty and adjustable gastric banding resulted in the least weight loss. Long term, high quality, and adequately powered trials are still needed to support the available evidence

Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI&gt;50 kg/m2. In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery. In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS). In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day &lt;3.3mmol/l and 20 and 40 minutes &lt; 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms. In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response. In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.

Made available in DSpace on 2014-12-17T14:13:58Z (GMT). No. of bitstreams: 1 IramiAF.pdf: 656108 bytes, checksum: 1ac30916d2a3afe1a1b29b6e3fa7c51f (MD5) Previous issue date: 2007-08-15 / The biliopancretic diversion with duodenal switch is one of the mixing techniques used in the treatment of morbid obesity. The duodenal switch reduces the stomach capacity and leaves only 50-100 cm of small intestine for nutrition and absorption. The surgery produces hormonal, structural and biochemical changes, which can influence on the result of scintigraphic examinations in operated patients. With the objective of evaluate the postoperative biodistribution of sodium pertechnetate (Na99mTcO4) in brain, thyroid, heart, lung, liver, spleen, kidney, stomach, duodenum, pancreas, small intestine, bladder, muscle and bone of Wistar rats. The rats were randomly allocated into 3 groups of 7 rats each: the duodenal switch group (DS), the control group (C) and the sham group (S). They were operated under anesthesia and aseptic technique. In the tenth postoperative day, 0.1mL of sodium pertechnetate was injected via orbital plexus. After 30 min the animals were killed with overdose of anesthetic and samples of liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, bone and brain were harvested, washed with saline and weighed. The detention of radioactivity was made using the automatic Gamma Counter Wizard, PerkinElmer and the percentage of activity per gram of tissue (%ATI/g) was calculated. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats (p<0.05). In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p>0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle. The study had the participation of the departments and laboratories researches, as Nucleus of Experimental Surgery, Department of Surgery, Laboratory of Radiobiology, Department of Pathology and Service of Nuclear Medicine, certifying the character of a multidisciplinary research / A cirurgia do desvio biliopancre?tico ? uma das t?cnicas mistas utilizada no tratamento da obesidade m?rbida. O Switch duodenal reduz o est?mago a ? de sua capacidade e deixa apenas 50-100 cm de intestino delgado para nutri??o e absor??o. Isso leva a altera??es estruturais, hormonais e bioqu?micas que podem influenciar no resultado de exames cintilogr?ficos de pacientes operados. Com o objetivo de avaliar a biodistribui??o p?s-operat?ria do pertecnetato de s?dio (Na99mTcO4) em ?rg?os de diversos sistemas como c?rebro, tire?ide, cora??o, pulm?o, f?gado, ba?o, rim, est?mago, duodeno, p?ncreas, intestino delgado, bexiga, m?sculo e f?mur de ratos Wistar submetidos ? t?cnica do switch duodenal, foram utilizados ratos com 3 meses de idade alocados aleatoriamente em: grupo tratado, submetido ? cirurgia de desvio biliopancre?tico, t?cnica do switch duodenal (SD), o grupo controle (C) e o grupo submetido a uma simula??o de cirurgia, denominado sham (S). No d?cimo dia de p?s-operat?rio, 0,1 mL do pertecnetato de s?dio (Na99mTcO4) foi injetado via plexo orbital (IV). Decorridos trinta minutos da administra??o do radiof?rmaco, os animais foram sacrificados e submetidos a toracolaparotomia mediana para retirada do f?gado, ba?o, p?ncreas, est?mago, duodeno, intestino delgado, tire?ide, pulm?o, cora??o, rim, bexiga, m?sculo, f?mur e c?rebro. A detec??o da radioatividade foi feita com Contador Gama (Wizard, PerkinElmer USA), autom?tico. Calculou-se em seguida o percentual de atividade por grama de tecido (%ATI/g) do pertecnetato de s?dio (Na99m TcO4) em cada ?rg?o. Os valores da biodistribui??o do pertecnetato no ba?o, p?ncreas e m?sculo nos animais do grupo switch tiveram uma diferen?a significativamente maior do que os dos grupos C e S (p<0,05). Na tire?ide dos animais do grupo SD o pertecnetato teve menor capta??o em rela??o aos demais grupos, sendo estatisticamente significante quando comparada ao grupo S (p<0,05). A biodistribui??o pulmonar nos animais do grupo SD s? foi significativamente maior quando comparada a do grupo S (p<0,05). N?o houve diferen?a significante, para os demais ?rg?os. Em conclus?o, a t?cnica do desvio biliopancre?tico com switch duodenal alterou a biodistribui??o p?s-operat?ria do Na99mTcO4 em ?rg?os como tire?ide, pulm?o, ba?o, p?ncreas e m?sculo de ratos operados, devido a prov?veis altera??es metab?licas e estruturais causadas por t?cnica cir?rgica mutilante. O trabalho teve um car?ter multidisciplinar com a participa??o de pesquisadores de diferentes departamentos e laborat?rios, como N?cleo de Cirurgia Experimental, Departamento de Cirurgia, Laborat?rio de Radiobiologia e o Servi?o de Medicina Nuclear da Liga Norte-Riograndense contra o C?ncer, atestando o car?ter multidisciplinar da pesquisa