Дисертації з теми "Diabète – chirurgie"
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Maanaoui, Mehdi. "La greffe d'îlots pancréatiques chez le patient diabétique transplanté rénal." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2023/2023ULILS071.pdf.
Pancreatic islet transplantation is an innovative cellular therapy for the management of diabetes in patients with type 1 diabetes. Currently, there are few studies that address the prognostic impact of islet transplantation in patients with type 1 diabetes who have received a kidney transplant or the determinants of transplantation success in this population. Furthermore, the definition of diabetes is evolving, with the dichotomy between type 1 and type 2 diabetes fading in favor of diabetes classifications based on the patient's clinical and biological phenotype. Pancreatic islet transplantation could potentially be expanded to other profiles of patients with diabetes and a kidney transplant, especially if there's evidence of insulin secretion deficiency. Thus, the objective of this thesis is to determine the role of pancreatic islet transplantation in patients with diabetes and a kidney transplant.In the first section, we present the results of a nationwide cohort study assessing the effect of pancreatic islet transplantation following kidney transplantation compared to insulin alone in patients with type 1 diabetes. Islet-after-kidney recipients were matched to control patients using a time-dependent propensity score. After matching, pancreatic islet transplantation is associated with a reduction in the combined risk of death and return to dialysis, as well as the isolated risk of death. This study emphasizes the importance of considering islet transplantation as a full-fledged therapeutic alternative, especially in regions where it is not reimbursed or available.The second section explores the determinants of islet loss of functionality, in particular the repercussions of alloimmunity. The results of a single-center study suggest that preformed DSA and early de novo DSA have little impact on islet transplantation outcomes, but late de novo DSA is temporally associated with impaired metabolic results. No cases of cross-sensitization between pancreatic islets and the underlying kidney in recipients were described, neither in the study nor in the literature.The last section focuses on evaluating the insulin profile in patients with type 2 diabetes and a kidney transplant, through the calculation of HOMA-2 scores, to extract the impact of insulin secretion. Analysis of a single-center retrospective cohort shows an association between insulin resistance evaluated by HOMA-2 and the risk of allograft loss, while insulin secretion was only associated with metabolic balance. However, given the relationship between metabolic balance and the likelihood of death and graft loss in kidney transplant patients with diabetes, pancreatic islet transplantation could be part of the therapeutic arsenal in a personalized medicine approach for these patients.In conclusion, this thesis advocates for personalized diabetes medicine in kidney transplant patients, promoting the integration of pancreatic islet transplantation as a key component in the therapeutic strategy for these individuals
Rouyer, Olivier. "Dysfonctions endothéliales après transplantation et diabète : Approches expérimentales et cliniques." Strasbourg 1, 2008. http://www.theses.fr/2008STR13075.
Among its many functions, vascular endothelium modulates vascular tone by secreting vasodilators and vasoconstrictors factors. Some diseases alter this balance, causing endothelial dysfunction which reduces organ perfusion and may jeopardizing the life. The work presented shows the interest of exploring endothelial dysfunction through endothelium-dependent relaxation studies, both in vitro through the analysis of aortic vascular ring reactivity in chamber organ and in vivo through flow-dependent dilatation of the humeral artery measurement, in response to a post-ischemic hyperaemia. In a model of aged rats with type 1 diabetes induced by streptozotocin, the late introduction of an IEC is deleterious on the exercise capacity. The normalization of blood pressure induced by the IEC could affect muscle perfusion. Endothelial function was not impaired and was not affected when the term of diabetes was lower. In a genetic model of Goto-Kakizaki rat type 2 diabetes, there was endothelial dysfunction related to the production of vasoconstrictors prostanoids. It was not improved by training even if training improved glycemic profile. In stable heart transplant patients with “normal” cardiac function, the persistent rise of plasma BNP values appeared to be related to endothelial dysfunction. While among hepatic transplant patients, normality of the endothelial function could be linked to the low prevalence of cardiovascular risk factors and a possible direct protective effect of Tacrolimus
Plourde, Charles-Étienne. "Les mécanismes de résolutions du diabète de type 2 induits par la chirurgie bariatrique." Mémoire, Université de Sherbrooke, 2015. http://hdl.handle.net/11143/6038.
Caiazzo, Robert. "Thérapie cellulaire du diabète : facteurs influençant la fonction primaire du greffon." Lille 2, 2009. http://www.theses.fr/2009LIL2S047.
Arapis, Konstantinos. "Mise au point de modèles précliniques de chirurgie bariatrique chez le rat rendu obèse par un régime hyperlipidique." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC086.
Favennec, Marie. "Etude de la voie des kynurénines dans l'obésité humaine." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S037/document.
Tryptophan, an essential amino acid, is either used in protein synthesis or metabolized via the serotonin or the kynurenine pathway. The kynurenine pathway is the main route of tryptophan degradation and generates several metabolites collectively called “kynurenines”. The expression of kynurenine pathway enzymes is induced by inflammatory mediators. Consequently kynurenine synthesis could be induced in individuals with obesity. In fact, obesity is characterized by a chronic low grade inflammation of the adipose tissue reflected by increased serum levels of inflammatory factors which are known to contribute to the development of obesity-induced insulino-resistance. Some metabolites of the kynurenine pathway have been proposed to be risk factors for the development of insulin resistance. Bariatric surgery is currently the most effective treatment for severe obesity and results in a significant weight loss, a decreased level of inflammatory factors and an amelioration of glucose homeostasis. The first enzyme of the kynurenine pathway, IDO1, is known to be more expressed in the adipose tissue of individuals with obesity compared to lean individuals. The kynurenine over tryptophan ratio reflects the activity of IDO1 and is also increased in individuals with obesity.Our objective was to characterize the expression of the kynurenine pathway enzymes in the adipose tissue of women with severe obesity and to evaluate serum levels of the kynurenine pathway metabolites to determine whether these factors could be associated with the appearance of diabetes. This study was performed in women with severe obesity with or without type 2 diabetes. Then we investigated the consequences of weight loss induced by bariatric surgery on levels of circulating kynurenines in order to evaluate whether these variations could explain the improvement in glucose control and type 2 diabetes remission after one year follow-up.In this study, we have shown that several kynurenine pathway enzymes were more expressed in the adipose tissue of women with obesity compared to lean controls. This increase is due to the presence of pro-inflammatory macrophages in the adipose tissue and also comes from the adipocyte response to inflammatory stimuli. In addition, we observed that the serum level of kynurenine and kynurenine over tryptophan ratio are higher in women with higher BMI and they both decrease one year after bariatric surgery. In addition, we observed that the serum level of kynurenine and kynurenine over tryptophan ratio are higher in women with higher BMI and they both decrease one year after bariatric surgery. As expected, bariatric surgery is associated with the improvement and even the remission of type 2 diabetes. We have shown that higher levels of kynurenic acid and quinolinic acid one year after the surgery are associated respectively with type 2 diabetes remission and better glucose homeostasis and that lower levels of xanthurenic acid are associated with better glucose homeostasis
Chavez, Talavera Oscar Manuel. "Rôle des acides biliaires dans la physiopathologie de l'obésité, la résistance à l'insuline, le diabète de type 2, la stéatose hépatique non alcoolique et dans le contexte de la chirurgie bariatrique Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease Bile Acid Alterations in Nonalcoholic Fatty Liver Disease, Obesity, Insulin Resistance and Type 2 Diabetes: What Do the Human Studies Tell?” Bile acids associate with glucose metabolism, but do not predict conversion to diabetes Bile acid alterations are associated with insulin resistance, but not with NASH in obese subjects Roux-en-Y gastric bypass increases systemic but not portal bile acid concentrations by decreasing hepatic bile acid uptake in minipigs The functional relevance of bile acids in the improvement of HDL-mediated endothelial protection after bariatric surgery Metabolic effects of bile acid sequestration: impact on cardiovascular risk factors." Thesis, Lille, 2019. http://www.theses.fr/2019LILUS057.
In addition to their role in the solubilization of dietary lipids, bile acids are signaling molecules regulating their own metabolism, glucose and lipid homeostasis, energy expenditure, cardiovascular function and inflammation via the activation of the Farnesoid X Receptor (FXR) and the Takeda G protein coupled Receptor 5 (TGR5). Indeed, changes in bile acid concentrations are associated with metabolic diseases and therefore they are candidates to participate in the pathophysiology of these diseases or predict their progression.In the first part of this thesis, we studied bile acid changes in the context of obesity, insulin resistance, type 2 diabetes and non-alcoholic steatohepatitis. We demonstrated that bile acids are correlated with glucose homeostasis in humans, but that they are not predictors for the progression from prediabetes to type 2 diabetes in a longitudinal cohort study.In the second part of this thesis, we studied the bile acids in the context of bariatric surgery. Our results showed that bariatric surgery reduces the hepatic recapture of certain bile acids, causing them to increase in the systemic circulation. Additionally, we showed that it is not the bile limb but the common limb the one responsible for metabolic changes after bariatric surgery in the minipig. Finally, we showed in humans that bile acids linked to high-density lipoproteins (HDL) increase after bariatric surgery, and that this increase is correlated with the restoration of their vasoprotective functions
Goncalves, Daisy. "Biodisponibilité de la bile et effets bénéfiques des chirurgies bariatriques de type by-pass." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10171/document.
Gastric bypass procedures have emerged as an effective treatment for morbid obese diabetic patientssince they provoke a rapid remission of diabetes before any weight loss has occurred. Patients also report adisinterest in high calorie food. A suggested mechanism associated a decrease in hepatic glucose production toan enhanced intestinal gluconeogenesis. Bile acids, described as inhibitors of gluconeogenesis, see theirbioavailability changed after these procedures. Indeed, they are absent in the alimentary limb while theirplasmatic concentration is increased. We therefore tested the hypothesis that plasma bile acids may inhibithepatic glucose production while their absence in the gut could induce intestinal gluconeogenesis.For this, we performed bile diversions matching the modified biliary flow occurring after gastric bypassprocedures. We showed that bile diversions lead to an increase in plasma bile acids. Bile diversions promote ablunting in hepatic glucose production whereas intestinal gluconeogenesis is increased in gut segments devoidof bile. Moreover, the modification of bile routing per se improves glucose control and dramatically decreasefood intake due to an acquired disinterest in fatty food. This data shows that bile routing modification is a keymechanistic feature in the beneficial outcomes of gastric bypass procedures
Amouyal, Chloé. "Restaurer la fonction bêta pancréatique de la souris leptine déficiente par la chirurgie bariatrique." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS010.
EGA (entero-gastro-anastomosis) is a gastric bypass procedure adapted to rodent. EGA in leptin deficient ob/ob mice improves glucose tolerance by increasing pancreatic insulin content and glucose stimulated insulin secretion in vivo without persistent body weight loss dietary restriction, modification of body composition / energy expenditure. We do not observe differences in islets ‘number or size after EGA. Insulin gene expression, beta-cell proliferation (Ki67 index) and insular immune infiltration are also unchanged. Transcriptomic analysis of pancreatic islets showed that bariatric surgery differentially regulated 193 genes and 27 miRs. Interestingly, the surgery normalized molecular defects (down regulation of TRPM5, GLUT2, GCK, connexin 36) and functional alteration (high sensitivity of islets to low glucose levels) observed in diabetic ob pancreatic islets. In addition, the surgery promoted the enrichment of 227 biological process, composed of genes with known or undetermined beta cell function, especially 21 genes are involved in the hormone transport and 20 genes in the hormone secretion biological process. Computational analysis predicted that 7 of 27 miRs (324-3p, 380-3p, 671-5p, 1927, 6904-5p, 6918-5p and 7682-3p) are hubs in the miRs-gene interaction network. Altogether, our data highlighted novel molecular mechanisms in the resolution of diabetes after bariatric surgery. Overall, diabetes resolution in our model appears to be totally independent of body weight
Spinelli, Valeria. "Les acides biliaires et la régulation de l’homéostasie métabolique : rôle du récepteur Farnesoid X Receptor (FXR) dans la cellule bêta-pancréatique : variation du pool des acides biliaires et chirurgie bariatrique Roux-en-Y Gastric Bypass." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S054.
Bile acids (BAs) are molecules produced in the liver, stored in the gallbladder, secreted into the intestine and returning to the liver via the enterohepatic circulation. A fraction of BAs escapes the reuptake by the liver and enters the systemic circulation, by which they reach the peripheral organs including the pancreas. Besides their function in facilitating the intestinal absorption of lipids, BAs are signaling molecules that act through receptors for BAs, which are expressed in the key tissues for metabolic regulation, and whose modulation by BAs contribute to regulate energy homeostasis. Thus, variations in the composition of the BAs pool determine the modulation of metabolism via their receptors. The BA-receptor Farnesoid-X receptor (FXR) is involved in the regulation of glucose, lipid and BA metabolism by its action in the liver, intestine, adipose tissue and pancreas. Whole body FXR deficient mice are glucose intolerant and insulin resistant in liver and peripheral tissues, whereas in a context of obesity, FXR deficiency rather improves these parameters. Furthermore, FXR is expressed in the pancreatic beta cell (bcell), where it regulates the synthesis and the secretion of insulin, but the molecular mechanisms have not been fully elucidated yet. To understand 1) the contribution of FXR bcell in the metabolic phenotype of the total FXRKO-mouse, and 2) the molecular mechanisms of the regulation of insulin production by FXR in the bcell, I developed a mouse model invalidated for FXR specifically in the bcell by the Cre-loxP strategy. The development of the model showed nonspecific recombination phenomena, and I developed a genotyping strategy to overcome this problem. To highlight the phenotype of the FXRKObcell mouse I tested various metabolic contexts (standard and high fat diet, fasting and refeeding conditions, circadian variations). Compared to control, FXRKO-bcell mice developed glucose intolerance and has lower insulinémia, defects increased by a high fat diet. The global transcriptomic analysis in the islets identified a set of microRNA strongly deregulated by invalidating FXR in the bcell, which could explain the dysfunctions in insulin secretion. Besides the modulation of the activity of the receptors, metabolic effects can be obtained by varying the composition of the pool of their ligands BAs. Thus, metabolic perturbations (such as insulin resistance and type 2 diabetes, obesity) are associated with qualitative and/or quantitative variations in the BA pool. In addition, variations of the BAs pool are associated to the metabolic improvement that precedes the weight loss after the surgical practice of Roux-en-Y Gastric Bypass (RYGB), which suggests that the BAs can be among the actors of the ‘weight loss-indipendent’ beneficial metabolic effects of RYGB. To investigate this hypothesis, some preclinical models of RYGB have been developed. During my thesis I compared the pool of BAs pre and post RYGB among three species (rat, pig and human; Coll. Prof. F. Pattou and Dr. E.Osto) with the aim of assessing which preclinical model is most suitable for these studies in terms of characteristics of the BAs pool. In a second study, I focused on the causes and mechanisms underlying the increased concentrations of circulating BAs induced by RYGB. In the model of minipig (coll. Pr. F. Pattou), the analysis of the plasma BA pool composition and the hepatic gene expression before and after RYGB, allowed to show that changes in the hepatic function are - at least in part - responsible for the increase of the BA pool following RYGB
Baud, Grégory. "Modulation de l’absorption intestinale postprandiale du glucose apès Roux-en-Y Gastric Bypass chez le miniporc." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S042/document.
Type 2 diabetes (T2D) is characterized primarily as a combined defect of insulin secretion and insulin action. For nearly a decade, the somewhat mysterious but spectacular benefit of metabolic surgery, and more specifically of Roux-en-Y gastric bypass (RYGB), on glucose control has been caused a questioning the current paradigm of T2D management. Gastro-intestinal exclusion by RYGB improves glucose metabolism, independent of weight loss. Although changes in intestinal bile trafficking have been shown to play a role, the underlying mechanisms are unclear. We performed RYGB in minipigs and showed that the intestinal uptake of ingested glucose is blunted in the bile deprived alimentary limb (AL). Glucose uptake in the AL was restored by the addition of bile, and this effect was abolished when active glucose intestinal transport was blocked with phlorizin. Sodium-glucose cotransporter 1 remained expressed in the AL, while intraluminal sodium content was markedly decreased. Adding sodium to the AL had the same effect as bile on glucose uptake. It also increased postprandial blood glucose response in conscious minipigs following RYGB. The decrease in intestinal uptake of glucose after RYGB was confirmed in humans. Our results demonstrate that bile diversion affects postprandial glucose metabolism by modulating sodium-glucose intestinal cotransport
Barataud, Aude. "Rôle de la néoglucogenèse intestinale et des récepteurs mu-opioïdes dans les effets bénéfiques du by-pass gastrique chez la souris." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10276/document.
Roux-en-Y gastric bypass procedure (GBP) is an obesity surgery that induces dramatic glucose homeostasis improvements independently of weight loss. A proposed mechanism to explain these glucose homeostasis improvements is an increase in intestinal glucose production (IGP) that induces beneficial effects on metabolism (satiety, improved liver insulin sensitivity). This increase in IGP is found in mice that have undergone a simplified GBP and is also responsible for the beneficial effects of protein-enriched diets through the inhibition of mu-opioid receptors (MOR) by alimentary peptides. We therefore hypothesized that the beneficial effects of GBP could depend on MOR inhibition by dietary proteins and we also tested the causal role of IGP in these metabolic improvements. For this purpose, we performed a duodenal-jejunal bypass surgery (DJB), ie GBP without gastric restriction, in wild-type mice (WT), in mice lacking MOR gene (MOR-/-) and in mice lacking IGP (IG6pc-/-). In obese mice, DJB induced a rapid and substantial weight loss (-30%), partly explained by fat malabsorption, and weight loss-dependent improvements of glucose homeostasis. In contrast, in the non-obese mice, DJB did not induce weight loss nor malabsorption but improved glucose tolerance. Effects were similar in WT, MOR-/- and I-G6pc-/- mice showing that mu-opioid receptors and IGP did not appear to have a causal role in glucose and energy metabolism improvements after DJB
Sterkers, Adrien. "Evaluation pré-clinique et clinique de l'autogreffe intramusculaire d'îlots de Langerhans." Phd thesis, Université du Droit et de la Santé - Lille II, 2013. http://tel.archives-ouvertes.fr/tel-00951952.
Payen, Cyrielle. "Implication des troubles métaboliques maternels sur la programmation fœtale des fonctions métabolique hépatique et vasculaire de la descendance." Thesis, Angers, 2019. http://www.theses.fr/2019ANGE0047.
In utero exposure to maternal metabolic pathologies leads to fetal programming, which increases the occurrence of metabolic, vascular and hepatic diseases in offspring. In this thesis, we focused on fetal programming induced by two types of maternal metabolic dysfunctions : obesity and diabetes. We highlighted that maternal obesity induced direct fetal programming of the vascular function in offspring regardless of metabolic disorders. In addition, we showed that disruption of perinatal nutrition leads to the early occurrence of metabolic disorders in offspring of obese mothers, without modifying the fetal programming of vascular function. Bariatric surgery doesn’t seem tobe able to reverse fetal programming of metabolic and vascular functions as described in obese mothers offspring. We also showed that fetal programming of vascular dysfunction of diabetic mother’s offspring can be transmitted from the F1 to the F2 generation. Finally, we highlighted the importance of sexual dimorphism in the fetal programming of vascular function. These results demonstrate that vascular (arterial hypertension) and metabolic (obesity, diabetes) diseases are not exclusively behavioral diseases but can also have a fetal life origin. They can be transmitted over several generations, thus contributing to explain the worldwide spread of obesity and associated metabolic disorders
Abdesselam, Inès. "Dépôts de graisse ectopique : étude de leur développement et de leur modulation." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5005.
The project of this thesis mainly focuses on ectopic lipid deposition development and their flexibility following therapeutic intervention. In our first study, we set out chronological order of ectopic fat onset and cardiac abnormalities in a high fat high sucrose mice model. Short duration exendin-4 treatment reverses every altered parameter. In the second study, we assessed treatment of obesity effect on cardiac ectopic fat deposition (EAT and steatosis), as well as hepatic and pancreatic fat at two different time points (6 months and 32 months) after bariatric surgery. We show significant reduction of every ectopic fat deposition, however in different kinetic. Finally, in a third study, we investigate birth weight effect on epicardial adipose tissue development. This study demonstrate important EAT accumulation in adulthood when birth weight is increased. Furthermore, birth weight and catch up growth in childhood between 2 and 12 years parameters impact significantly the development of epicardial fat.In summary, these results provide better understanding of ectopic fat deposition development and modulation
Raucoules-Aimé, Marc. "Administration peroperatoire d'insuline chez le diabetique : influence de la severite de l'acte operatoire, du type de diabete et des modalites d'administration par voie veineuse." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX22952.
Chopard-Lallier, Sophie. "Suivi fonctionnel de la greffe d'îlots de Langerhans : interêt de l'imagerie IRM et de l'immuno-monitoring cellulaire." Thesis, Besançon, 2013. http://www.theses.fr/2013BESA3001.
Langerhans islet transplantation allows curingtype 1 diabetes by restoring an endogenous insulin secretion. Halfof patients will resume insulin withinyears. This loss of function may be explained by the lack of monitoring tools able to diagnose an ongoing graft failure. The aims of our work were toevaluate the efficiency of MRI to diagnose islet graft rejection, and to assess the feasibility of immune cellular monitoring in transplanted patients.MRI in the rat mortelMethods: Syngeneic, allogeneic and xenogeneic islets were transplanted intra-portally to diabetic rats after labeling with superparamagnetic ironoxide nanoparticles (ferucarbotran). Images were acquired on a clinical 3T MRI scanner.Results: The signal decreasing was different between the 3 types of transplantations. At day 4, the MRI signal in allogeneic group was significantlylower while glycaemia remained normal. With a cut-off value of 84% at day 4, sensitivity of 91% and specificity of 70% were obtained.Cellular immune monitoringMethods: Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients and splenocytes from donors. Immunereactivity was assessed by the release of IFNy (ELISpot), cell prolifération (flow cytometry of Ki67), and cytokine quantification (Bioplex). Theresults were correlated to the islet graft function assessed by (5-score.Results: Patients with low islet function showed higher cellular reactivity against donor cells assessed by ELISpot IFNy ((p=0,007, r=-0,50) andproliferation index (p=0,006, r=-0,51). Patients with low graft function had higher levels of IFNy, IL-5 and 1L-17
Cavin, Jean-Baptiste. "Gastrointestinal plasticity in health and diseases : what we have learned from bariatric surgeries." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC143/document.
In today’s global epidemic of obesity, more and more people are undergoing bariatric surgery, which is the best known treatment available to lose weight and treat obesity-associated diseases. Yet, little is known about gastrointestinal (GI) adaptation and its metabolic consequences after surgery. We developed original models of Roux-en-Y gastric bypass (RYGB), mini-bypass (MGB) and vertical sleeve gastrectomy (VSG) in rats, and we characterized the morphological and functional adaptations of the GI epithelium after these surgeries in order to understand the origin of the observed metabolic improvements. We reported profound changes in the remaining gastric mucosa of rats having undergone RYGB and VSG, suggesting an increase in acid production by parietal cells and an impaired production of gastrin and ghrelin. In RYGB rats and patients, the alimentary limb was hyperplasic and intestinal glucose consumption was increased. After VSG, the absorption of glucose during meals appeared diminished. These adaptations could participate in the lowering of blood glucose after surgery. In addition, the increased number of enteroendocrine cells observed in RYGB rats and patients, and their increased density in VSG rats, could contribute to the higher secretion of incretin hormone and improved glycemic control in operated individuals. Finally, we demonstrated in rats that the MGB was more malabsorptive than the RYGB. Indeed, we observed an increased fecal loss of nitrogen and energy despite intestinal overgrowth and higher expression of peptide transporters. This thesis brings new insight to the role of the GI tract in the metabolic outcomes of bariatric surgeries
Olivi, Elena <1982>. "Adipose-derived stem cells and tissue revascularization: enhancing islet survival and performance for diabetes care." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5603/1/Olivi_Elena_tesi.pdf.
Olivi, Elena <1982>. "Adipose-derived stem cells and tissue revascularization: enhancing islet survival and performance for diabetes care." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5603/.
Muccini, Natascia <1980>. "Diabete ed ischemia critica degli arti inferiori. Valutazione degli indicatori sierologici di danno di parete: determinazione quantitativa delle cellule endoteliali circolanti mature." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6611/1/TESI_MUCCINI.pdf.
OBJECTIVE: To quantify the number of circulating endothelial mature cells (EMC) in patients with critical limb ischemia (CI), and if correlations exit with risk factors, clinical stage and the number of cEMC. Evaluate the vascular structure changes (calcification and inflammatory infiltrate) and angiogenesis (number of capillary/arterial slice) of arterial wall. METHODS: Between 2006, may, and 2008, april, we’ve enrolled in a prospective study patients with CI scheduled for surgery. Demographic data, risk factors, clinical stage according to Leriche-Fontaine, type of surgery have been collected and stored in a database. For every patient 2 ml of blood have been sampled for immunomagnetic quantification of cEMC, so as a sample of the arterial wall. RESULTS: Thirtythree patients (25 males, 75,8%), aged 34-91, average 71years old, with CI underwent surgical revascularization have been enrolled. Twentyeight patients (84.8%) had a IV stage PAOD, chronic heart ischemia (60.6%), hypertension (72.7%) and diabetes mellitus type II (66.6%). The average concentration of cEMC/ml is significant higher (p=0.001) in patients with CI (cEMC=531.24, range 107-3330) than in control cases (cEMC =125.8, range 19-346). Also patients with diabetes type II have a higher concentration of cEMC than the non-diabetic patients (726.7/mm vs 325.5/ml vs.), with a p<0.05. Arterial wall of pts. with diabetes , compared with control group, revealed a higher incidence of complex arterial lesions (66% vs. 47%) and a lower capillary density (65% vs. 87%). CONCLUSION: cEMC are a reliable marker of vascular wall damage. Their concentration is higher in patients with diabetes, hypertensive disease. In patients with diabetes type 2 we’ve found a minor angiogenic capability with more calcifications and inflammatory infiltrate, showing a more serious damage
Muccini, Natascia <1980>. "Diabete ed ischemia critica degli arti inferiori. Valutazione degli indicatori sierologici di danno di parete: determinazione quantitativa delle cellule endoteliali circolanti mature." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6611/.
OBJECTIVE: To quantify the number of circulating endothelial mature cells (EMC) in patients with critical limb ischemia (CI), and if correlations exit with risk factors, clinical stage and the number of cEMC. Evaluate the vascular structure changes (calcification and inflammatory infiltrate) and angiogenesis (number of capillary/arterial slice) of arterial wall. METHODS: Between 2006, may, and 2008, april, we’ve enrolled in a prospective study patients with CI scheduled for surgery. Demographic data, risk factors, clinical stage according to Leriche-Fontaine, type of surgery have been collected and stored in a database. For every patient 2 ml of blood have been sampled for immunomagnetic quantification of cEMC, so as a sample of the arterial wall. RESULTS: Thirtythree patients (25 males, 75,8%), aged 34-91, average 71years old, with CI underwent surgical revascularization have been enrolled. Twentyeight patients (84.8%) had a IV stage PAOD, chronic heart ischemia (60.6%), hypertension (72.7%) and diabetes mellitus type II (66.6%). The average concentration of cEMC/ml is significant higher (p=0.001) in patients with CI (cEMC=531.24, range 107-3330) than in control cases (cEMC =125.8, range 19-346). Also patients with diabetes type II have a higher concentration of cEMC than the non-diabetic patients (726.7/mm vs 325.5/ml vs.), with a p<0.05. Arterial wall of pts. with diabetes , compared with control group, revealed a higher incidence of complex arterial lesions (66% vs. 47%) and a lower capillary density (65% vs. 87%). CONCLUSION: cEMC are a reliable marker of vascular wall damage. Their concentration is higher in patients with diabetes, hypertensive disease. In patients with diabetes type 2 we’ve found a minor angiogenic capability with more calcifications and inflammatory infiltrate, showing a more serious damage
Hildenbrand-Joie, Céline Ziegler Olivier. "Plaie chirurgicale du talon chez le diabétique quels sont les facteurs pronostiques /." [S.l.] : [s.n.], 2003. http://www.scd.uhp-nancy.fr/docnum/SCDMED_T_2003_HILDENBRAND_JOIE_CELINE.pdf.
Orrico, Catia <1972>. "Diabete ed ischemia critica degli arti inferiori. Studio del danno della parete arteriosa e del ruolo dell'endotelio circolante nella riparazione tessutale e nella neoangiogenesi." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1739/1/Orrico_Catia_tesi.pdf.
Orrico, Catia <1972>. "Diabete ed ischemia critica degli arti inferiori. Studio del danno della parete arteriosa e del ruolo dell'endotelio circolante nella riparazione tessutale e nella neoangiogenesi." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1739/.
Lugrin, Didier. "Réponse endocrino-métabolique à l'anesthésie générale et à la chirurgie chez le diabétique comparée au sujet sain." Bordeaux 2, 1989. http://www.theses.fr/1989BOR23071.
Belligoli, Anna. "Adipose tissue and insulin secretion in the pathophysiology of obesity and its complications." Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3421917.
L’obesità e il diabete mellito tipo 2 (T2DM) sono due patologie strettamente correlate tra loro e, insieme, rappresentano una delle maggiori emergenze sanitarie a livello mondiale. I meccanismi fisiopatologici che legano le due patologie, non sono ancora stati completamente spiegati. Infatti, mentre sono abbastanza note le alterazioni che portano dall’aumento del peso corporeo alla comparsa di T2DM, meno noti sono i motivi per cui non tutti i pazienti obesi sviluppano la patologia diabetica. Per spiegare tale paradosso, alcuni studi si sono concentrati sulla possibile diversa capacità di espansione del tessuto adiposo (TA). Come tutti i tessuti, anche il TA, per poter espandersi, necessita di un’adeguata consensuale vascolarizzazione. E’ stato ipotizzato che un’alterata angiogenesi durante l’espansione del TA in alcuni soggetti, e la presenza di un danno a livello del microcircolo dello stesso TA, possano influire negativamente sul peggioramento del profilo glicemico. In alcuni modelli di animali, affetti da diabete e obesità, si sono evidenziate alterazioni a carico del microcircolo del TA e a carico del potenziale adipogenico. Consensualmente, alcuni studi sul TA dell’uomo, hanno suggerito che l’obesità porta ad una alterazione dell’angiogenesi a livello del TA con contemporanea comparsa di uno stato ipossico a sua volta responsabile della risposta infiammatoria e profibrotica. Infiammazione e fibrosi, hanno un ruolo fondamentale nello sviluppo dell’insulino-resistenza e quindi del T2DM. Inoltre, è noto che il tessuto adiposo viscerale (VAT) rappresenta il deposito di TA con maggior grado di infiammazione, mentre il tessuto adiposo sottocutaneo (SAT) è considerato un tessuto meno infiammato e in grado di avere un ruolo protettivo nei confronti dello sviluppo delle patologie metaboliche. Nonostante ciò, è possibile ipotizzare che con l’aumento progressivo del peso corporeo anche il SAT acquisisca caratteristiche disfunzionali come il VAT. Sulla base di questi presupposti, abbiamo deciso di analizzare le possibili variazioni in termini di morfologia, di densità capillare, di quantità di precursori adipogenici, di potenziale adipogenetico sia nel SAT che nel VAT di pazienti obesi e di pazienti normopeso normoglicemici. Inoltre, tra i pazienti obesi, sulla base delle caratteristiche cliniche e biochimiche, abbiamo selezionato coloro che erano normoglicemici (ob N), pre-diabetici (ob pre-T2DM) e diabetici (ob T2DM). Sono, quindi, stati raccolti campioni di SAT e/o il VAT da 249 pazienti divisi nei 4 gruppi sopra descritti: 18 pazienti normopeso e normoglicemici (18.5 < BMI < 24,9 kg/m2), 68 ob N, 65 ob pre-T2DM e 57 ob T2DM. Abbiamo, inoltre, avuto l’opportunità di analizzare il SAT di 41 pazienti obesi dopo significativo calo ponderale (ob WL). I campioni di TA sono stati studiati (1) mediante analisi immunocitochimica, al fine di valutare la morfologia degli adipociti e la densità capillare, (2) mediante analisi citofluorimetrica della frazione vasculo stromale (FVS) per quantificare la presenza di precursori adipocitari (CD45-CD34+CD31-) e di precursori endoteliali (CD45-CD34+CD31+), (3) attraverso la coltura dei preadipociti estratti dalla FVS, per valutare il potenziale adipogenetico; (4) mediante espressione genica di leptina, PPRγ, VEGFA, VEGF2 e HIF1-α. L’analisi dei nostri dati ci ha permesso di confermare che il tessuto adiposo dei soggetti obesi è significativamente meno vascolarizzato, sia nel SAT che, dato ad oggi non noto, nel VAT, rispetto al tessuto adiposo dei soggetti magri. Diversamente da quanto ipotizzato, la presenza di un alterato profilo glicemico, come quello presente nel pre-diabete, o la presenza di un diabete franco, non peggiorano ulteriormente la vascolarizzazione del TA, né nel SAT, né nel VAT. Ciò che si modifica in maniera significativa e precoce è l’architettura del TA. Infatti, già nei pazienti ob pre-T2DM e, anche nei pz ob T2DM, abbiamo osservato un progressivo aumento del diametro degli adipociti. Inoltre, nel TA dei pazienti con alterato profilo glicemico abbiamo osservato una significativa riduzione sia nella percentuale dei preadipociti presenti nella FVS sia nella loro capacità di differenziare in vitro. Questi dati ci permettono di ipotizzare che il TA dei pazienti con alterato profilo glicemico cresce maggiormente per ipertrofia che per iperplasia e che il ”primum movens” nello sviluppo della patologia diabetica è da ricercare nelle modificazioni a carico della cellula adiposa più che nelle modificazioni del microcircolo del tessuto adiposo sia nel VAT ma, anche nel SAT. Inoltre, considerando il progressivo incremento nell’utilizzo della chirurgia bariatrica per trattare sia l’aumento di peso ma anche le complicanze metaboliche a esso correlate, è stato eseguito uno studio sugli effetti della sleeve gastrectomy per via laparoscopica (LSG) a distanza di un anno dall’intervento. Mentre gli effetti positivi di questa procedura chirurgica sono ormai noti, meno noti sono gli effetti collaterali; in particolare, l’ipoglicemia post prandiale è stata ben descritta dopo intervento di by pass gastrico ma resta ancor poco indagata dopo intervento di LSG. Abbiamo, pertanto, reclutato 197 pazienti obesi non diabetici sottoposti a LSG e li abbiamo studiati prima e a distanza di un anno dall’intervento bariatrico. In tutti i pazienti è stata raccolta la storia clinica, è stato eseguito esame obiettivo e sono stati eseguiti gli esami bioumorali comprensivi di screening endocrino-metabolico completo, incluso OGTT prolungato a 180 minuti, e dosaggio delle citochine infiammatorie. Un anno dopo l’intervento, tutti i pazienti hanno avuto una significativa riduzione del peso corporeo e del BMI, un significativo miglioramento dei parametri metabolici, compreso il profilo glicemico e insulinemico, e una significativa riduzione delle citochine infiammatorie. Il 32,8% dei pazienti ha sviluppato un’ipoglicemia severa dopo test provocativo (OGTT). I pazienti con ipoglicemie hanno mostrato un peso e un BMI significativamente minore rispetto ai pazienti che non hanno sviluppato ipoglicemia e una percentuale di perdita di BMI significativamente maggiore. L’ipoglicemia si è dimostrata essere più frequente in quei pazienti che, prima dell’intervento, erano più giovani, con un peso e un BMI inferiore e con livelli di trigliceridemia superiori ai pazienti che non avevano sviluppato ipoglicemie dopo LSG.
Hartmann, Dorothea Regina [Verfasser], and Christian [Gutachter] Jurowich. "Untersuchung früh-postoperativer Effekte bariatrischer Chirurgie auf Diabetes mellitus Typ 2 – Identifizierung von Non-Respondern / Dorothea Regina Hartmann ; Gutachter: Christian Jurowich." Würzburg : Universität Würzburg, 2018. http://d-nb.info/1154386589/34.
Schiller, Julia Virginie. "Venöse Revaskularisation bei Vorliegen einer Mikro- und Makroangiopathie." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-71990.
Objective: Many patients with significant arterioclerosis of the heart cannot benefit from a coronary artery bypass and other methods because they have macroangiopathy combined with microangiopathy. We evaluated the efficiency of venous revascularization in minipigs with macroangiopathy combined with microangiopathy in a chronic model of 3 months. Histological analysis of arterial and venous vessels of the heart was conducted. Methods: In left anterior descending artery (LAD) microspheres (diameter 100µm) were injected in 24 minipigs (12 control group, 12 therapy group). 7 weeks later a stenosis of the LAD was performed in both groups with an average of 84,6 ± 4,3%. In therapy group left internal thoracic artery was anastomosed to the concomitant vein of the LAD in beating heart surgery. The flow of bypass was proved in angiography and the flow rate was measured by ultrasound. 10 weeks later bypass of therapy group and stenosis of both groups were verified in angiography. At the beginning of every part of the experiment the ejection fraction in both groups was evaluated with echocardiography. Hemodynamic monitoring was performed throughout the experiment. In histological analysis arterial and venous vessels in left atrium, right atrium, septum and area of anastomosis were evaluated in the thickness of wall and area of lumen. Results: In ejection fraction a significant difference between control and therapy group was seen. After performing the bypass, the ejection fraction in therapy group increased, while it decreased in control group in the same period of time of 10 weeks. In the histological analysis a non-classifiable type of vessel was found only in the area of the anastomosis. The vessel had a a large area of lumen and a thick wall due to media hyperplasia. Conclusion: Venous revascularization of the concomitant vein of the LAD via bypass of the left thoracic artery in a chronic model improves cardiac funcion and is therefore an effective method when having microangiopathy and macroangiopathy combined. The non-classifiable type of vessel are most likely arterialized veins which underwent a structural change of the wall due to the arterial blood pressure
GIRIBONO, Anna Maria. "Trattamento endovascolare con nuovi materiali in pazienti diabetici affetti da ischemia critica e lesioni trofiche degli arti inferiori: risultati a medio termine." Doctoral thesis, Università degli studi del Molise, 2021. http://hdl.handle.net/11695/100849.
Objective: Diabetes mellitus is a main cause of lower limb amputation worldwide. It is currently a very common disease, more than 425 million people are affected and this number is expected to double after 2045. A person with diabetes has a significant risk, up to 25% more than non-diabetics, of developing trophic ulcers throughout his life. In recent years, thanks to the development of new technologies and new materials, the endovascular treatment has now become the therapeutic option of first choice. The purpose of this thesis is to analyze the short and medium term results of endovascular treatment performed with different types of materials in patients suffering from critical ischemia of the lower limbs. In particular, the primary, primary assisted and secondary patency, the restenosis / occlusion and limb salvage rate were assessed. Methods: Eighty diabetic patients with concomitant peripheral arterial disease were enrolled in two different vascular surgery centers respectively in South and North Italy, AOU Federico II in Naples and AOU Maggiore della Carità in Novara and treated with different types of devices; in a group of these a new type of stent was used: SUPERA® (Abbott Vascular, Santa Clara, CA, USA). All patients underwent preoperative an ultrasound Doppler of the lower limbs, a calculation of the ankle-arm index, foot x-ray, microbiological swab and targeted antibiotic therapy in case of trophic lesions, calculation of the BMI. Results: All revascularization procedures were performed under local anesthesia. From February 2018 to March 2020, 80 patients (69M/11F) were treated at the two reference centers. A control echocolordoppler was performed at 3,6,12,18 and 24 months. Technical success was 100%. The primary, primary assisted and secondary patency of the entire population under examination were respectively 73.8%, 86% and 90% at 24 months. In the subgroup of patients treated with Supera® stents, they were 75%, 90.6% and 87.5% at 24 months, respectively. The limb salvage rate for all patients was over 90%. Conclusions: The endovascular treatment in patients with ischemic diabetic foot is now the first choice therapeutic option, thanks to the development of new technologies and new materials.
Signac, Angélique. "Bilan de deux années de réadaptation de patients amputés vasculaires du membre inférieur." Bordeaux 2, 1997. http://www.theses.fr/1997BOR2M110.
Cunin, Claude. "Greffes intracérébroventriculaires de noyaux hypothalamiques : Études histophysiologiques chez le rat brattleboro déficient génétique en vasopressine." Nancy 1, 1986. http://www.theses.fr/1986NAN10009.
Pietramaggiori, Giorgio. "Integrazione di forze meccaniche, fattori circolanti e matrici extracellulari: un nuovo paradigma in ingegneria dei tessuti." Doctoral thesis, Università degli studi di Padova, 2007. http://hdl.handle.net/11577/3425015.
Taleb, Nadine. "L’efficacité du pancréas artificiel externe durant l’exercice chez les adultes atteints de diabète de type 1." Thèse, 2016. http://hdl.handle.net/1866/18885.
Background: Physical activity is often avoided by patients with Type 1 diabetes (T1D) despite its health benefits due to fear of its elevated hypoglycemic risk. The external artificial pancreas is a new technology that controls glucose via a closed-loop strategy of three components; a continuous glucose monitoring system (CGMS), an algorithm and an insulin pump. Studies of the artificial pancreas included physical activity sessions but were rarely designed to specifically assess its efficacy during exercise. Moreover, the precision of the CGMS can be affected by the rapidly changing blood glucose levels during exercise. Objectives: 1) To test and compare the efficacy of the two versions of the artificial pancreas, single-hormone (insulin only) and dual-hormone (insulin plus glucagon) during two types of exercise, continuous and interval, in patients with T1D. 2) To compare the performance of two CGMS, Dexcom and Enlite, at rest and during exercise. Results: 1) During single-hormone artificial pancreas in comparison to dual-hormone, 31.2% of the participants had at least one hypoglycemic episode necessitating treatment vs. 9% (p=0,02) and 24.4 ± 27.6 % of the time spent in hypoglycemia (plasma glucose < 4 mmol/l) vs. 4.4 ± 14.3% (p=0.0001), respectively. 2) The mean relative absolute differences (MARD) in reference to plasma glucose for Dexcom vs. Enlite were at rest 13.8 vs. 12.4% (p=0.53) and during exercise 22.5% vs. 20.4% (p=0.58). The comparison of mean ARD`s at rest vs. exercise were significant for Dexcom (p=0.005) and Enlite (p=0.007). Conclusions: The dual-hormone artificial pancreas was shown to be better than single-hormone at achieving hypoglycaemia-free control during exercise in adults with T1D. Dexcom and Enlite demonstrated comparable overall performances during rest and physical activity with a lower accuracy for both sensors during exercise.
Leroux-Stewart, Josée. "Effets cardiométaboliques de la restriction calorique seule ou en combinaison avec l’activité physique dans le diabète de type 2." Thèse, 2016. http://hdl.handle.net/1866/18871.
Type 2 diabetes (T2D) is a chronic disease characterized by high blood sugar that can lead to many complications with potential morbid outcomes. Alarmingly, the worldwide prevalence is increasing at a high rate mainly du to aging and harmful lifestyle habits. In fact, inactivity and poor food choices are at the heart of an obesity epidemic that plays a crucial role in the pathogenesis of T2D. Lifestyle modifications thus play an important role in patient care. However, it remains uncertain which therapy between a caloric restriction (CR) alone or a combination of CR plus physical activity (PA) should be encouraged to achieve better reduction in fat mass and in epicardial fat thickness. The latter represents the visceral fat depot of the heart and is emerging as an important marker for predicting and stratifying cardiovascular risk. The objective of this Master’s thesis is to better characterize the independent effects of CR and PA on total fat mass, epicardial fat, and overall cardiometabolic profile of patients with T2D. To achieve this, a randomized controlled 16-week trial was performed, with 73 patients randomized to 1 of 3 groups (Control, CR, or CR+PA), while aiming for a similar caloric deficit in both intervention groups. Results showed that the combination of CR+PA allows a larger reduction of fat mass and epicardial fat thickness. However, these findings did not translate into significant differences in cardiometabolic improvements between groups. These results now need to be validated in larger cohorts with longer follow-ups.
Patková, Barbora. "Bariatrická chirurgie a kompenzace diabetu." Master's thesis, 2018. http://www.nusl.cz/ntk/nusl-387229.
Benjamim, de Oliveira Adriana. "Évolution échocardiographique et prédicteurs de progression de la sténose valvulaire aortique." Thèse, 2014. http://hdl.handle.net/1866/11795.
Manolescu, Daniel-Constantin. "Impacts métaboliques et thérapeutiques de la vitamine A, sous forme d’acide rétinoïque, dans l’obésité, la résistance à l’insuline et le diabète de type 2 chez la souris ob/ob = Metabolic and Therapeutic Impacts of Vitamin A as Retinoic Acid on Obesity, Insulin Resistance, and Type 2 Diabetes in ob/ob Mice." Thèse, 2018. http://hdl.handle.net/1866/21808.
Hartmann, Dorothea Regina. "Untersuchung früh-postoperativer Effekte bariatrischer Chirurgie auf Diabetes mellitus Typ 2 – Identifizierung von Non-Respondern." Doctoral thesis, 2018. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-156714.
Background: Diabetes surgery in nonobese or moderately obese patients is an emerging topic. The identification of preoperative factors predicting diabetes outcome following bariatric surgery, especially for metabolic nonresponders, is imperative. Methods: Between 2005 and 2011, 235 patients underwent bariatric surgery for morbid obesity. Eighty-two of 235 patients had type 2 diabetes mellitus (T2DM). Data from this subgroup were investigated with univariate and multivariate analyses to identify predictors for metabolic nonresponse after surgery. Results: Diabetes did not improve in 17/82 patients within 3 months after surgery. No correlation between excess body weight loss and metabolic response was detected. In univariate analysis, preoperative duration of diabetes was significantly longer in the nonresponder group (9.146 vs. 6.270 years; *p 0.016), preoperative HbA1c levels were significantly higher among the nonresponders than among the responders (8.341 vs. 7.781 %; *p 0.033), and more patients in the nonresponder group were reliant on a multi-drug approach preoperatively (*p 0.045). In multivariate analysis, age, preoperative doses of insulin, and preoperative oral antidiabetics showed positive correlation to metabolic nonresponse after surgery (*p 0.04; *p 0.021; *p 0.021). Metabolic failure rate was lower after Roux-en-Y gastric bypass compared to other bariatric procedures (**p 0.008). Conclusions: A long history of preoperative T2DM, high preoperative HbA1c levels, and a preoperative therapy consisting of diverse approaches to diabetes treatment may be factors predicting failure of diabetes improvement in the early postoperative course after bariatric surgery. Age, preoperative insulin, and oral antidiabetic medication can be regarded as independent, significant predictors for metabolic outcome after bariatric surgery
Nosso, Gabriella. "REMISSIONE DEL DIABETE MELLITO DI TIPO 2 DOPO CHIRURGIA BARIATRICA: MECCANISMI FISIOPATOLOGICI E SIGNIFICATO CLINICO." Tesi di dottorato, 2015. http://www.fedoa.unina.it/10362/1/Tesi%20Dottorato%20GabriellaNosso.pdf.
ZENTI, MARIA GRAZIA. "Effetti di diverse tecniche di Chirurgia Bariatrica sull’Omeostasi Metabolica in pazienti Obesi." Doctoral thesis, 2014. http://hdl.handle.net/11562/693959.
Bariatric surgery can lead to improvement or even resolution of type 2 diabetes Mellitus (T2DM) with the spectrum of responses depending also on operation procedures. However, many underlying mechanisms of metabolic action of different surgical techniques are still unclear. The aim of this study was evaluate the long-term effects of bariatric surgery on weight loss and T2DM remission and to provide a better understanding of the effects of surgery on β-cell function and incretin secretion. METHODS: The study included 104 obese T2DM patients (66 women and 38 men, ) who were wait-listed for laparoscopic gastric banding (LAGB, 11 subjects, age 47,3±2,9 y, BMI 42,3±2,5 kg/m2), or for laparoscopic Roux-en-Y gastric bypass (RYBP , 77 subjects, age 49,7±0,1 y, BMI 45,7±0,7 kg/m2), or for sleeve gastrectomy (SG, 16 subjects, age 50,9±2,3 y, BMI 50,7±2,2 kg/m2) In 5 patients a mixed meal tolerance test (MMT: 186 Kcal; 53% carbohydrate, 30% fat, 17% protein) was performed before and 1 and 12 months after RYBP to assess hormonal changes. During MMT blood samples were collected for 300 minutes for the measurement of plasma glucose, insulin, C-peptide, lactate and GIP. β-cell function parameters were derived from mathematical modelling of plasma glucose, insulin and C-peptide concentrations. Body composition, fat mass and fat-free mass were evaluated before and 1 and 12 months after RYBP by means of DEXA. RESULTS: The average percentage of weight loss after surgery in the 104 patients was 26,5±1,46% and it was maintained at 24 and 36 months follow-up. Diabetes remission at 3 years follow-up occurred in 56,5% of study participants (in 50,0% of LAGB, 56% of RYBP and 100% of SG). Duration of diabetes was the only significant predictor of diabetes remission at 2 and 3 years. The 5 patients who underwent MMT (according to ClinicalTrials.gov protocol NCT 01767441), showed, 1 month after RYBP, a significant weight loss: ΔBMI=- 4,07±0,26 kg/m2 p<0,001, Δtotal mass= -10,62±0,61 kg, Δtotal-fat= -5,58±0,74 kg p<0,007. HOMA-IR and plasma insulin decreased (HOMA-IR 17,2±4,8 vs 2.7±0.61 p=0,04; plasma insulin 231,36±21,17 vs 64,92±4,41 pmol/L, p=0,02) as well as insulin AUC and lactate AUC (respectively 66,43±10,5 vs 28,67±5,51 nmol/l in 4 hour; p=0,039 and 258,03±34,76 vs 183,77±32,89 mmol/l in 4 hour; p=0,02). Insulin secretion rate significantly improved (p<0,04). CONCLUSIONS Bariatric Surgery appears to be a viable option for the treatment of severe obesity, resulting in long term weight loss and frequent diabetes remission. Our preliminary data suggest that amelioration in glucose homeostasis, evaluated by a physiological stimulus (MMT), could be related to improvement in β-cell function and insulin sensitivity.
Schlinkert, Pia. "Charakterisierung des Einflusses bariatrischer Chirurgie auf die β-adrenerge Signalkaskade und damit verbundene Adaptationsprozesse im Glukose- und Fettsäuremetabolismus". 2019. https://tud.qucosa.de/id/qucosa%3A75418.
Stingl, Maria-Theresa. "Kurz- und Langzeitergebnisse des laparoskopischen Gastric Banding (eine retrospektive Studie an 127 Patienten)." Doctoral thesis, 2009. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-38672.
The Laparoscopic Adjustable Gastric Banding (LAGB) has become a common bariatric procedure. Within this study 127 patients were analysed retrospectively after LAGB in terms of preoperative characteristics, weight loss, co-morbidities, short and long-term complications and quality of life. 60 patients were operated using the pergastric pathway (PG), 67 patients were operated using the pars flaccida technique (PF). The median follow-up was 63 month. Mean excess body weight loss (EBWL %) was 50.6 %. 39 patients experienced one ore more postoperative complications. The most frequent complications were slippage and pouch dilatation (34 %). Mortality rate was 0 %. Two-thirds of the patients reported an increase in quality of life after LAGB. Comparing the two different operation techniques (PF and PG-technique) there was no difference in weight loss or reduction of co-morbidities. In accordance with similar studies we documented a lower postoperative complication rate in the pars flaccida group. Especially the very frequent complications slippage and pouch dilatation occurred significantly less often using the pars flaccida technique
CACCIABAUDO, Francesco. "STUDIO SPERIMENTALE SU PANCREAS DI MAIALE PER L’OTTENIMENTO DI CELLULE PRODUCENTI INSULINA." Doctoral thesis, 2014. http://hdl.handle.net/10447/85546.
Rikkala, Prashanth Reddy. "Regulation of the Na+-D-glucose cotransporter SGLT1 in the small intestine in response to bariatric surgery and peptides derived from protein RS1 (RSC1A1)." Doctoral thesis, 2015. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-130608.
Bariatrische Operationen repräsentieren die Behandlung erster Wahl bei krankhafter Fettleibigkeit, resultierend in Gewichtsverlust und verbesserter Diabetes-Kontrolle. Der positive Effekt bariatrischer Operationen auf den Typ-2 Diabetes ist unklar. Erhöhte Sekretion von Insulin, welches das Enterohormon „Glucagon-like-peptide 1“ (GLP-1) reguliert, wurde beobachtet bei Ratten mit experimentellem Typ 2-ähnlichem Diabetes nach duodenalem-jejunalem Bypass (DJB) und ilealer Transposition (IT). Der Natrium-abhängige Glucose Cotransporter (SGLT1) ist beteiligt an der Sekretion von GLP-1, das wiederum die Insulin-Sekretion reguliert. In der vorliegenden Studie wurde der Versuch unternommen, die Bedeutung von DJB und IT für den durch SGLT1 vermittelten Glucose-Transport aufzuklären. Transportmessungen der durch Phlorizin hemmbaren Aufnahme des SGLT1-spezifischen Glucose-Analogs [14C] α-Methyl-D-glucopyranosid (AMG) wurden durchgeführt, um die durch diese chirurgischen Eingriffe bedingten Änderungen des Transports durch SGLT1 zu bestimmen. Die Daten deuten darauf hin, dass DJB die SGLT1-vermittelte Glucose Absorption im Dünndarm verringert, was zu einer körpergewichts-unabhängigen Verbesserung des Diabetes Typ 2 beiträgt. Aber IT veränderte den SGLT1-vermittelten Glucose-Transport nicht. Immunhistochemische Analysen zeigten, dass bei IT das transponierte Ileum einen vergrößerten Durchmesser, eine erhöhte Länge der Villi und eine erhöhte Anzahl der GLP-1 sekretierenden L-Zellen aufwies. Die gewichtsunabhängige Verbesserung der glykämischen Kontrolle nach IT steht nicht im Zusammenhang mit der durch SGLT1-vermittelten Glucose-Absorption, sondern könnte verbunden sein mit einer erhöhten GLP-1 Sekretion. Damit einhergehend fokussiert sich die Studie auch auf die Regulation des SGLT1 durch verschiedene, von RS1 abgeleitete Tripeptide in Darm-Gewebe von Maus und Mensch (ex vivo). Die phlorizin-hemmbare Aufnahme von AMG wurde gemessen mit und ohne Tripeptide. QEP und thiophosphoryliertes QSP regulierten die SGLT1-Aktivität herunter im Dünndarm auf eine konzentrationsabhängige Weise. Unter den getesteten Tripeptiden zeigte QEP eine höhere Aktivität und weitere Analysen in verschiedenen Spezies zeigten seine universelle Rolle in der SGLT1-Regulation.Die Daten zeigen daher, dass die von RS1 abgeleiteten Tripeptide QEP und thiophosporyliertes QSP eingesetzt werden könnten zur Behandlung von Typ2 Diabetes
Griffo, Ettore. "ASSE ENTERO-INSULARE E METABOLISMO GLICO-LIPIDICO NEL DIABETE DI TIPO 2 E NELL’OBESITÀ: EFFETTI DELLA CHIRURGIA BARIATRICA E DI DIVERSI INTERVENTI NUTRIZIONALI." Tesi di dottorato, 2014. http://www.fedoa.unina.it/9678/1/Ettore_Griffo_26.pdf.
Schiller, Julia Virginie. "Venöse Revaskularisation bei Vorliegen einer Mikro- und Makroangiopathie." Doctoral thesis, 2010. https://ul.qucosa.de/id/qucosa%3A11241.
Objective: Many patients with significant arterioclerosis of the heart cannot benefit from a coronary artery bypass and other methods because they have macroangiopathy combined with microangiopathy. We evaluated the efficiency of venous revascularization in minipigs with macroangiopathy combined with microangiopathy in a chronic model of 3 months. Histological analysis of arterial and venous vessels of the heart was conducted. Methods: In left anterior descending artery (LAD) microspheres (diameter 100µm) were injected in 24 minipigs (12 control group, 12 therapy group). 7 weeks later a stenosis of the LAD was performed in both groups with an average of 84,6 ± 4,3%. In therapy group left internal thoracic artery was anastomosed to the concomitant vein of the LAD in beating heart surgery. The flow of bypass was proved in angiography and the flow rate was measured by ultrasound. 10 weeks later bypass of therapy group and stenosis of both groups were verified in angiography. At the beginning of every part of the experiment the ejection fraction in both groups was evaluated with echocardiography. Hemodynamic monitoring was performed throughout the experiment. In histological analysis arterial and venous vessels in left atrium, right atrium, septum and area of anastomosis were evaluated in the thickness of wall and area of lumen. Results: In ejection fraction a significant difference between control and therapy group was seen. After performing the bypass, the ejection fraction in therapy group increased, while it decreased in control group in the same period of time of 10 weeks. In the histological analysis a non-classifiable type of vessel was found only in the area of the anastomosis. The vessel had a a large area of lumen and a thick wall due to media hyperplasia. Conclusion: Venous revascularization of the concomitant vein of the LAD via bypass of the left thoracic artery in a chronic model improves cardiac funcion and is therefore an effective method when having microangiopathy and macroangiopathy combined. The non-classifiable type of vessel are most likely arterialized veins which underwent a structural change of the wall due to the arterial blood pressure.:1. Einleitung 7 1.1. Patienten ohne therapeutische Option 7 1.2. Das therapeutische Dilemma bei gleichzeitigem Vorliegen einer Mikro- und Makroangiopathie 8 1.3. Therapieoption - venöse Revaskularisation 10 1.4. Vorversuch 12 1.5. Fragestellung 14 2. Methodik 15 2.1. Versuchskonzept 15 2.2. Versuchsbeschreibung 16 2.2.1. Vorgehensweise vor der Operation 16 2.2.1.1. Vorbereitung 16 2.2.1.2. Narkose 17 2.2.2. Medikation 17 2.2.3. Versuchsprotokoll 19 2.2.3.1. Versuchsteil 1: Induktion der Mikroangiopathie durch Mikropsphären 19 2.2.3.2. Versuchsteil 2: Herzinfarkt, venöse Revaskularisation (Therapiegruppe) 20 2.2.3.3. Versuchsteil 3: Herzkatheteruntersuchung, Herzexplantation 24 2.3. Erhobene Parameter und Untersuchungen 26 2.3.1. Echokardiographie 26 2.3.2. Herzkatheteruntersuchung 27 2.3.3. Ultraschallflussmessung 28 2.3.4. Bestimmung der Enzyme 29 2.3.5. Elektrokardiographie 29 2.3.6. Messung des mittleren arteriellen Blutdrucks 29 2.3.7. Blutgasanalyse 30 2.3.8. Entnahme Herz 30 2.4. Histologische Methodik und Auswertung 30 2.4.1. Herstellung der histologischen Schnitte 30 2.4.2. Protokoll der Hämatotoxilin Eosin- Färbung für Paraffinschnitte 31 2.4.3. Auswertung Histologie 31 2.5. Lyse 32 2.6. Statistik 33 3. Materialien 34 3.1. Versuche 34 3.1.1. Minipigs 34 3.1.2. Medikamente 34 3.1.3. Materialien 35 3.1.4. Geräte 35 3.2. Histologische Aufarbeitung 36 3.2.1. Materialien 36 3.2.2. Geräte 36 3.3. Lyse 37 3.3.1. Materialien 37 3.3.2. Geräte 37 3.4. Statistische Datenanalyse 37 4. Ergebnisse 38 4.1. Allgemeine Charakteristika der Versuchstiere 38 4.1.1. Vergleich Therapiegruppe und Kontrollgruppe 38 4.1.2. Komplikationen/Ausfälle 39 4.2. Funktionelle Ergebnisse 40 4.2.1. Auswertung Mikroangiopathie 40 4.2.1.1. Herzkatheteruntersuchung 40 4.2.1.2. Funktionelle Befunde 43 4.2.1.3. Ergebnisse Lyse 43 4.2.2. Echokardiographie - Ejektionsfraktion 44 4.2.3. Herzkatheteruntersuchung - Auswertung Makroangiopathie 45 4.2.4. Ultraschallflussmessung 45 4.2.5. Enzymbestimmung 45 4.2.6. Elektrokardiographie und hämodynamische Parameter 47 4.2.6.1. Elektrokardiographie – ST-Veränderungen 47 4.2.6.2. Herzfrequenz 48 4.2.6.3. Mittlerer arterieller Blutdruck 49 4.2.6.4. Systolischer und diastolischer Blutdruck 49 4.3. Histologische Ergebnisse 51 4.3.1. Vergleich Gefäße in verschiedenen Bereichen des Herzens 51 4.3.2. Nicht klassifizierter Gefäßtyp 53 5. Diskussion 58 5.1. Versuchsmodell 58 5.1.1. Auswahl der Versuchstiere 58 5.1.2. Mikroangipathie 58 5.1.3. Makroangiopathie 59 5.1.4. Operationskonzept 60 5.1.4.1. Auswahl des Bypassgrafts 60 5.1.4.2. Beating heart Chirurgie 61 5.1.5. Auswertung der Ergebnisse 62 5.2. Umbau des Gefäßsystems 67 5.3. Limitationen des Modells 71 5.3.1. Anzahl Versuchstiere 71 5.3.2. Methodik und funktionelle Parameter 72 5.4. Mögliche klinische Anwendungen der Operationstechnik 74 6. Zusammenfassung der Arbeit 77 7. Literaturverzeichnis 79 8. Anhang 87 9. Danksagung 92
PERBELLINI, Filippo. "Adipose and cardiac progenitor cells for regenerative medicine." Doctoral thesis, 2014. http://hdl.handle.net/11562/694159.
Cardiovascular diseases, and the progression to heart failure, are one of the leading cause of death. Diabetes is often associate with cardiovascular complications because of the disturbed substrate metabolism that can alter the homeostasis of the tissues and modify the progenitor cell populations. Most adult tissues have a mesenchymal progenitor cell subpopulation that represents a proportion of the total cell number and which, because of its regenerative properties, is an attractive source for cell therapy. Recently it has been proved that injection of mesenchymal cells improve contractile function in rodents following myocardial infarction. The aim of this study was to isolate, characterize and differentiate adipose-derived mesenchymal stem cells (ADMSCs), and cardiosphere-derived cells (CDCs), and to determine the effect of simply a high fat diet on these two mesenchymal populations. Cardiac explant-derived and cardiosphere-derived cells (EDCs, CDCs) were cultured from atrial tissue and adipose stem cells were cultured from epididymal fat depots after collagenase digestion. Cultured ADMSCs contained more CD90+ cells (47% vs 87%) and fewer DDR2+ and CD45+ cells compared to freshly isolated ADMSCs (respectively 9% and 20% vs 38% and 42%). Various media were tested to validate the differentiation capacity of adipose mesenchymal cells, but only the TGFβ-supplemented medium was able to increase the expression of cardiac specific genes. Hypoxia increased cell proliferation and changed the surface marker profile of ADMSCs; more DDR2+ cells and fewer CD45+ and CD90+ cells were found compared to normoxic ADMSCs. In vitro expansion of neonatal cardiac fibroblasts and cardiosphere-derived cells revealed a similarity between these two cell populations, both increased proliferation and clonogenic capacity with time in culture and expressed mesenchymal/fibroblast markers such as CD90 and DDR2. CDCs were able to acquire a cardiac phenotype in vitro, increasing gene expression of cardiac actin and troponin T, however no beating cells were observed. After 4 months of high-fat diet (55% fat; HFD,) mice had raised fed plasma glucose, cholesterol and insulin levels and decreased plasma lactate. Significantly more ADMSCs were obtained from high fat fed animals and ADMSC numbers correlated with plasma glucose, cholesterol and lactate. Expression of CD45, DDR2 and CD105 were increased in ADMSCs from high fat fed mice and the functional properties and differentiation capacity were slightly decreased. No differences in surface marker expression and functional properties were detected between high fat and chow diet mice CDCs. In conclusion, four months of HFD induced a diabetic phenotype in C57 Black 6 mice. The high fat diet increased ADMSCs yield but modified the balance of ADMSCs populations and decreased their differentiation capacity. In contrast, cardiac progenitor cells were unaffected by induction of the diabetic phenotype.
COCCIA, FEDERICA. "Obesità severa e nafld in pazienti con e senza diabete tipo 2 prima e dopo chirurgia bariatrica: studio degli indici non invasivi di steatosi e fibrosi e dei livelli plasmatici di acidi biliari come predittori di severità dell’istologia epatica." Doctoral thesis, 2020. http://hdl.handle.net/11573/1363031.
Purpose: in morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population. Methods 90 morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All non diabetic patient (n=77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS). Results: In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50% and significant fibrosis 14%. New cutoffs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR and ARFI increased with fibrosis grade (p0.03, p 0.008, p 0.04, p 0.05 respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02). Conclusions: In morbid obese subjects, we calculated new cutoffs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.