Introduction: Historically, type 2 diabetes (T2DM) has been regarded as a progressive and degenerative disease and only minority of patients can have disease remission with conventional treatment. It was noticed that gastrointestinal surgery could induce complete remission of T2DM in most of morbidly obese patients. Compared to the West, the development of bariatric and metabolic surgery is slow in Hong Kong. It is unknown whether the knowledge and attitudes of medical doctors and patients towards surgical treatment for T2DM have impacts on the development in this field. The novel procedure sleeve gastrectomy (SG) had been shown to be effective in inducing T2DM remission in obese human. Duodenal jejunal bypass (DJB) and ileal transposition (IT) were reported to be effective for ameliorating T2DM in non-obese diabetic animal model. The anti-diabetic potency of DJB and IT is unknown in comparing to SG particularly in non-obese subjects. Currently, SG is the main procedure for morbidly obese patients with or without T2DM in the authors’ institution. Aims: The aims of the present thesis were to investigate the knowledge and attitudes of medical doctors and patients toward using surgery as a treatment for T2DM, to compare the anti-diabetic effect of SG, DJB and IT in non-obese T2DM animal model, and lastly, to review of outcomes of morbidly obese patients who underwent SG in authors’ institution. Methods: Survey was conducted using questionnaire for interview of both doctors and patients to investigate their knowledge and attitudes toward surgical treatment of T2DM. The anti-diabetic effects of novel surgical procedures SG, DJB and IT were compared using non-obese T2DM animal model (Goto Kakizaki rats). The outcomes were evaluation by measuring fasting glucose and glycosylated haemoglobin (HbA1c) levels. Other parameters including alteration in gut hormones and lipid profile were also analyzed. The outcomes of morbidly obese patients who underwent laparoscopic SG in last 5 years in the authors’ institution were retrospectively reviewed. Results: The knowledge of bariatric and metabolic surgery was inadequate both in medical doctors and patients. The attitude and pattern of referral from medical doctors depends on the amount of knowledge. Patients’ attitudes were positive and they accept surgery as a treatment option for T2DM as long as they were provided with adequate information. This implies that tremendous educational works are required both for medical doctors and patients for the development of bariatric and metabolic surgery in Hong Kong. All 3 procedures (SG, DJB and IT) significantly improved glucose homeostasis and the effect was more potent and durable in DJB and IT than SG. The improved glucose homeostasis in IT was resulted from increased GLP-1 and PYY secretion (hindgut theory). In DJB, GIP, GLP-1 and PYY were raised and the anti-diabetic effect could be explained both by the foregut and hindgut theories. SG reduced the diet triglyceride absorption. DJB reduced cholesterol absorption whereas IT reduced cholesterol but increase triglyceride absorption. The outcomes of SG for T2DM for morbidly obese patients were promising. More than 90% patients had T2DM ameliorated and 70% had complete remission. SG can effectively control the body weight of morbidly obese patients. Conclusion: Education, both to doctors and patients, was crucial to overcome the potential obstacles for the development of this newly specialty. The anti-diabetic effects of DJB and IT were more potent than SG in non-obese diabetic animal model. The lipid absorption varied in different surgical procedures. Application of these procedures in non-obese T2DM patients warrants individual consideration and further investigation. SG in the authors’ institution was effective to induce T2DM remission in morbidly obese patients. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Objective. To assess the influence of diabetes mellitus on early morbidity and mortality following open vascular surgical interventions. Methods. Clinical data on patients subjected to open vascular surgical procedures over a 5 year period at the Durban Metropolitan Vascular Service was culled from a prospectively maintained computerized database. They were divided according to the type of surgical procedure performed. These were open abdominal aortic surgery, peripheral bypass surgery, lower extremity major amputation and carotid endarterectomy. They were further subdivided into 2 groups, diabetic and non-diabetic. Results. 1104 charts were analysed. There were no significant differences in demographics and risk factors between the two groups. 273 patients had open abdominal aortic surgery. 217 (79%) were non-diabetic. diabetic patients had significantly higher incidence of myocardial infarction (p=0.00001) (6 of 6 patients), graft sepsis (p=0.000001) (7 of 7 patients) and mortality rate (p=0.0335) (5 of 10 patients). 337 patients had peripheral bypass procedures. 204 (60%) of these were non-diabetic. There was a high prevalence of smokers among non-diabetics and of hypertension among diabetics. Diabetic patients had a preponderance of graft infection (p=0.0015) (15 of 20 patients) and cardiovascular complications (p=0.0072) (7 of 8 patients). 230 patients had lower extremity major amputations, 81 (35%) were diabetic and 149 (65%) non-diabetic. Myocardial infarction and death (6 of 8 patients each) were significantly higher among diabetics (p =0.04). 264 patients had carotid endarterectomy, 170 (64%) being non-diabetic. The surgical outcome was similar between the two groups. Conclusions. This is retrospective study and as such it has some its limitations. Not all patients might have been included in the study and some of the information might have been lost. The numbers in this study are large and these limitations would appear not to have influenced the outcome of this study. This study has shown that diabetes mellitus had diverse influence on the early outcome following different vascular surgical procedures. Diabetes mellitus significantly increased the incidence of graft sepsis among those who had aorto-bifemoral bypass and peripheral bypass procedures. The incidence of peri-operative cardiovascular morbidity was significantly increased among diabetics who had peripheral bypass procedures, open abdominal aortic surgery and lower extremity major amputations. Diabetes mellitus had no influence on the surgical outcome following carotid endarterectomy. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

O Diabetes Mellitus tipo 2 (DM2) é uma síndrome multifatorial com complicações graves e mortalidade significativa, mas seu tratamento até o momento tem mostrado resultados desapontadores. Apenas 50% dos pacientes com DM2 conseguem manter níveis glicêmicos adequados. Rubino et al em 2004 demonstraram uma técnica cirúrgica de exclusão duodenojejunal em ratos diabéticos não obesos com bons resultados no controle dos níveis glicêmicos. O desenvolvimento de uma técnica que não apresente perda ponderal pode prover base teórica e científica para justificar sua aplicação em pacientes com DM2 e IMC<35. Com este objetivo, iniciamos um estudo experimental utilizando a técnica proposta por Marchesini em 2008, que consiste na secção do duodeno imediatamente após o piloro, seguido de duodenojejunostomia com anastomose termino-lateral na porção média do intestino delgado. O objetivo foi demonstrar as alterações no perfil metabólico, inflamatório e de estresse oxidativo após a cirurgia metabólica. Foram utilizados 24 ratos Wistar com 2 dias de vida sendo que em 16 deles foi induzido o DM2 através de injeção i.p. de 100mg/kg de Streptozotocina. O desenvolvimento de diabetes foi confirmado após 10 semanas através de TTGIP. Oito ratos diabéticos compuseram o grupo diabético cirúrgico (DM+OP) e oito o grupo diabético controle (DM). Os outros oito animais que não tiveram indução do diabetes formaram o grupo controle clínico (CO). A técnica de Marchesini foi realizada no grupo DM+OP, e os grupos DM e CO receberam dieta padrão e seguimento. Foi realizado TTGIP aos 7, 15, 30, 60 e 90 dias após a cirurgia, quando os animais foram submetidos a eutanásia. Os animais do DM+OP não tiveram perda de peso importante após três meses da cirurgia, enquanto que o DM e o CO tiveram aumento significativo do peso. A glicemia dos animais operados foi significativamente menor no grupo operado em comparação ao diabético controle e os valores de colesterol seguiram a mesma tendência. Os níveis de TNF-α, NF-kB, SOD, TBARS e Catalase foram significativamente menores no grupo DM+OP em relação ao grupo DM. A duodenojejunostomia foi efetiva em controlar os níveis de glicemia e colesterol, bem como diminuiu significativamente os marcadores inflamatórios e de estresse oxidativo. / Diabetes Mellitus type 2 (DMT2) is a multifactorial syndrome with severe complications and significant mortality. Until this moment, its treatment has proven disappointing. Only 50% of DM2 patients are able to maintain proper glycemic levels. In 2004 Rubino et al showed a surgical technique of duodenal-jejunal exclusion in diabetic non-obese rats with positive results in the control of glycemic levels. The development of a technique that does not imply weight loss may provide a theoretical and scientific basis for its application in DM2 patients who present BMI<35. With this aim, this experimental study was conducted using the technique proposed by Marchesini in 2008, which consists of a section of the duodenum immediately next to the pylorus, followed by duodenojejunostomy with end-to-side anastomosis in the medial portion of the small intestine. The objective was to demonstrate alterations in the metabolic and inflammatory profile and in oxidative stress after metabolic surgery. An amount of 24 2-day-old Wistar rats were used. In 16 of them DMT2 was induced through 100mg/kg injection i.p. of streptozotocin. The development of diabetes was confirmed after 10 weeks through TTGIP. Eight diabetic rats composed the diabetic surgical group (DM+OP); and 8 other rats composed the diabetic control group (DM). The other 8 animals which were not induced formed the clinical control group (CO). The Marchesini technique was used in the DM+OP, and the other groups received the standard diet and follow up. TTGIP was performed at 7, 15, 30, 60 and 90 days after surgery, when the animals were submitted to euthanasia. DM+OP animals presented no important weight loss 3 months after surgery, while the other groups presented a significant weight gain. Weight maintenance after surgery in DM+OP proves the effectiveness of this technique in preventing obesity progression, which is characteristic in obese diabetic patients. The glucose levels were significantly lower in the operated group compared to diabetic control and cholesterol values followed the same trend. The levels of TNF-a, NF-kB , SOD, catalase and TBARS were significantly lower in DM + OP group compared to DM. The duodenojejunostomy was effective in controlling blood glucose levels and cholesterol, and significantly decreased inflammatory markers and oxidative stress.

O Diabetes Mellitus tipo 2 (DM2) é uma síndrome multifatorial com complicações graves e mortalidade significativa, mas seu tratamento até o momento tem mostrado resultados desapontadores. Apenas 50% dos pacientes com DM2 conseguem manter níveis glicêmicos adequados. Rubino et al em 2004 demonstraram uma técnica cirúrgica de exclusão duodenojejunal em ratos diabéticos não obesos com bons resultados no controle dos níveis glicêmicos. O desenvolvimento de uma técnica que não apresente perda ponderal pode prover base teórica e científica para justificar sua aplicação em pacientes com DM2 e IMC<35. Com este objetivo, iniciamos um estudo experimental utilizando a técnica proposta por Marchesini em 2008, que consiste na secção do duodeno imediatamente após o piloro, seguido de duodenojejunostomia com anastomose termino-lateral na porção média do intestino delgado. O objetivo foi demonstrar as alterações no perfil metabólico, inflamatório e de estresse oxidativo após a cirurgia metabólica. Foram utilizados 24 ratos Wistar com 2 dias de vida sendo que em 16 deles foi induzido o DM2 através de injeção i.p. de 100mg/kg de Streptozotocina. O desenvolvimento de diabetes foi confirmado após 10 semanas através de TTGIP. Oito ratos diabéticos compuseram o grupo diabético cirúrgico (DM+OP) e oito o grupo diabético controle (DM). Os outros oito animais que não tiveram indução do diabetes formaram o grupo controle clínico (CO). A técnica de Marchesini foi realizada no grupo DM+OP, e os grupos DM e CO receberam dieta padrão e seguimento. Foi realizado TTGIP aos 7, 15, 30, 60 e 90 dias após a cirurgia, quando os animais foram submetidos a eutanásia. Os animais do DM+OP não tiveram perda de peso importante após três meses da cirurgia, enquanto que o DM e o CO tiveram aumento significativo do peso. A glicemia dos animais operados foi significativamente menor no grupo operado em comparação ao diabético controle e os valores de colesterol seguiram a mesma tendência. Os níveis de TNF-α, NF-kB, SOD, TBARS e Catalase foram significativamente menores no grupo DM+OP em relação ao grupo DM. A duodenojejunostomia foi efetiva em controlar os níveis de glicemia e colesterol, bem como diminuiu significativamente os marcadores inflamatórios e de estresse oxidativo. / Diabetes Mellitus type 2 (DMT2) is a multifactorial syndrome with severe complications and significant mortality. Until this moment, its treatment has proven disappointing. Only 50% of DM2 patients are able to maintain proper glycemic levels. In 2004 Rubino et al showed a surgical technique of duodenal-jejunal exclusion in diabetic non-obese rats with positive results in the control of glycemic levels. The development of a technique that does not imply weight loss may provide a theoretical and scientific basis for its application in DM2 patients who present BMI<35. With this aim, this experimental study was conducted using the technique proposed by Marchesini in 2008, which consists of a section of the duodenum immediately next to the pylorus, followed by duodenojejunostomy with end-to-side anastomosis in the medial portion of the small intestine. The objective was to demonstrate alterations in the metabolic and inflammatory profile and in oxidative stress after metabolic surgery. An amount of 24 2-day-old Wistar rats were used. In 16 of them DMT2 was induced through 100mg/kg injection i.p. of streptozotocin. The development of diabetes was confirmed after 10 weeks through TTGIP. Eight diabetic rats composed the diabetic surgical group (DM+OP); and 8 other rats composed the diabetic control group (DM). The other 8 animals which were not induced formed the clinical control group (CO). The Marchesini technique was used in the DM+OP, and the other groups received the standard diet and follow up. TTGIP was performed at 7, 15, 30, 60 and 90 days after surgery, when the animals were submitted to euthanasia. DM+OP animals presented no important weight loss 3 months after surgery, while the other groups presented a significant weight gain. Weight maintenance after surgery in DM+OP proves the effectiveness of this technique in preventing obesity progression, which is characteristic in obese diabetic patients. The glucose levels were significantly lower in the operated group compared to diabetic control and cholesterol values followed the same trend. The levels of TNF-a, NF-kB , SOD, catalase and TBARS were significantly lower in DM + OP group compared to DM. The duodenojejunostomy was effective in controlling blood glucose levels and cholesterol, and significantly decreased inflammatory markers and oxidative stress.

O Diabetes Mellitus tipo 2 (DM2) é uma síndrome multifatorial com complicações graves e mortalidade significativa, mas seu tratamento até o momento tem mostrado resultados desapontadores. Apenas 50% dos pacientes com DM2 conseguem manter níveis glicêmicos adequados. Rubino et al em 2004 demonstraram uma técnica cirúrgica de exclusão duodenojejunal em ratos diabéticos não obesos com bons resultados no controle dos níveis glicêmicos. O desenvolvimento de uma técnica que não apresente perda ponderal pode prover base teórica e científica para justificar sua aplicação em pacientes com DM2 e IMC<35. Com este objetivo, iniciamos um estudo experimental utilizando a técnica proposta por Marchesini em 2008, que consiste na secção do duodeno imediatamente após o piloro, seguido de duodenojejunostomia com anastomose termino-lateral na porção média do intestino delgado. O objetivo foi demonstrar as alterações no perfil metabólico, inflamatório e de estresse oxidativo após a cirurgia metabólica. Foram utilizados 24 ratos Wistar com 2 dias de vida sendo que em 16 deles foi induzido o DM2 através de injeção i.p. de 100mg/kg de Streptozotocina. O desenvolvimento de diabetes foi confirmado após 10 semanas através de TTGIP. Oito ratos diabéticos compuseram o grupo diabético cirúrgico (DM+OP) e oito o grupo diabético controle (DM). Os outros oito animais que não tiveram indução do diabetes formaram o grupo controle clínico (CO). A técnica de Marchesini foi realizada no grupo DM+OP, e os grupos DM e CO receberam dieta padrão e seguimento. Foi realizado TTGIP aos 7, 15, 30, 60 e 90 dias após a cirurgia, quando os animais foram submetidos a eutanásia. Os animais do DM+OP não tiveram perda de peso importante após três meses da cirurgia, enquanto que o DM e o CO tiveram aumento significativo do peso. A glicemia dos animais operados foi significativamente menor no grupo operado em comparação ao diabético controle e os valores de colesterol seguiram a mesma tendência. Os níveis de TNF-α, NF-kB, SOD, TBARS e Catalase foram significativamente menores no grupo DM+OP em relação ao grupo DM. A duodenojejunostomia foi efetiva em controlar os níveis de glicemia e colesterol, bem como diminuiu significativamente os marcadores inflamatórios e de estresse oxidativo. / Diabetes Mellitus type 2 (DMT2) is a multifactorial syndrome with severe complications and significant mortality. Until this moment, its treatment has proven disappointing. Only 50% of DM2 patients are able to maintain proper glycemic levels. In 2004 Rubino et al showed a surgical technique of duodenal-jejunal exclusion in diabetic non-obese rats with positive results in the control of glycemic levels. The development of a technique that does not imply weight loss may provide a theoretical and scientific basis for its application in DM2 patients who present BMI<35. With this aim, this experimental study was conducted using the technique proposed by Marchesini in 2008, which consists of a section of the duodenum immediately next to the pylorus, followed by duodenojejunostomy with end-to-side anastomosis in the medial portion of the small intestine. The objective was to demonstrate alterations in the metabolic and inflammatory profile and in oxidative stress after metabolic surgery. An amount of 24 2-day-old Wistar rats were used. In 16 of them DMT2 was induced through 100mg/kg injection i.p. of streptozotocin. The development of diabetes was confirmed after 10 weeks through TTGIP. Eight diabetic rats composed the diabetic surgical group (DM+OP); and 8 other rats composed the diabetic control group (DM). The other 8 animals which were not induced formed the clinical control group (CO). The Marchesini technique was used in the DM+OP, and the other groups received the standard diet and follow up. TTGIP was performed at 7, 15, 30, 60 and 90 days after surgery, when the animals were submitted to euthanasia. DM+OP animals presented no important weight loss 3 months after surgery, while the other groups presented a significant weight gain. Weight maintenance after surgery in DM+OP proves the effectiveness of this technique in preventing obesity progression, which is characteristic in obese diabetic patients. The glucose levels were significantly lower in the operated group compared to diabetic control and cholesterol values followed the same trend. The levels of TNF-a, NF-kB , SOD, catalase and TBARS were significantly lower in DM + OP group compared to DM. The duodenojejunostomy was effective in controlling blood glucose levels and cholesterol, and significantly decreased inflammatory markers and oxidative stress.