GIP和减重手术.ppt

GIP and Bariatric Surgery,Contents,背景介绍,GIP相关知识,减重手术,综述结论,5,2,3,4,1,背景知识,治疗T2DM的两种理论,背景介绍,减重手术(Bariatric Surgery)是目前治疗病态肥胖症最有效的治疗方法,同时可以治疗肥胖合并症如2型糖尿病（T2DM）、高血压、高血脂等。但目前减重手术减肥和治疗T2DM的治病机理存在争议。传统认为减重手术阻碍食物吸收和引起消化不良是减肥和改善T2DM的唯一治疗机制。现在发现Bariatric Surgery之后改变了一些胃肠激素的分泌和作用，减轻体内胰岛素抵抗而起治疗作用。其中GIP的生理作用及手术后的改变备受争议。,GIP相关知识,GIP在人体中的生理作用,GIP在肥胖者和T2DM体内的作用,GIP和GLP-1的不同,减重手术如何引起GIP的改变,GIP在人体中的生理作用,GIP主要由分布于十二指肠和空肠的k细胞分泌，在健康人体中主要有以下生理作用： 1、GIP是一个生理性肠降血糖素，有葡萄糖依赖的促胰岛素分泌作用； 2、GIP能引起餐后胰高血糖素的升高； 3、GIP能预防胰岛细胞的凋亡和促进胰岛细胞的增殖； 4、GIP能促进葡萄糖的吸收、葡萄糖转化为脂肪酸及脂肪在脂肪组织的沉积； 5、GIP妨碍骨质吸收，促进骨的形成； 6、GIP对人体胃能动性作用小。,GIP和GLP-1的不同,GIP在肥胖者和T2DM体内的作用,The cause of this GIP resistance is down -regulation（下调）of GIP receptors in type 2 diabetic patients . It is important to note that certain polymorphisms of TCF7L2 protein are associated with GIP resistance. Animal experiments have shown that high fat diet causes a proliferation(增生) of GIP producing K cells in the duodenum.,GIP在肥胖者和T2DM体内的作用,GIP在肥胖者和T2DM体内的作用,结论： GIP在肥胖者和T2DM体内含量增加，这导致胰岛素抵抗和葡萄糖依赖胰岛素分泌功能受损。因此降低患者体内GIP含量可用来治疗肥胖型T2DM.,减重手术如何引起GIP的改变,减重手术如何引起GIP的改变,In a study by Rudnicki et al. on rats, it was found that the presence of food and bile（胆汁） is necessary for the secretion of GIP. GIP can explain the findings of this experiment as preventing exposure of the proximal gut to digested food (food + bile) causes decreased secretion of GIP. 结论：减重手术改变了食物的流向，使十二直肠和空肠处的k细胞营养缺乏，因此导致k细胞分泌GIP的量减少。,治疗T2DM的理论,后肠道理论 （The hindgut theory）,肠道理论,前肠道理论 （The foregut theory）,后肠道理论 （The hindgut theory）,减重手术使食物提前进入回肠，食物刺激诱导后肠激素分泌，这种激素被认为是GLP-1 ，它可以调控胰岛内分泌功能，增加胰岛素的合成和/或释放，改善外周组织对胰岛素敏感性，从而达到控制糖尿病的作用 。,前肠道理论 （The foregut theory）,手术前，糖尿病易感者的上消化道经食物刺激产生“胰岛素抵抗因子”，使人体产生胰岛素抵抗现象。手术后，营养物质避开对胃十二指肠的刺激，减少“胰岛素抵抗因子”等物质的释放，导致2型糖尿病的胰岛素拮抗减轻或消失。研究认为这种胰岛素抵抗因子对抗GIP作用。,两种理论的争议,Wang et al. showed in an experiment using a non-obese rat model that the duodenojejunal bypass (a foregut operation) and the ileal transposition (a hindgut operation) are equivalent in terms of weight loss and decrease in blood glucose levels. 结论：研究发现两种理论可能都成立，减肥手术中它们共同起作用。,减重手术,Roux-en-Y胃旁路术( Roux-en-Y gastric bypass RYGB) 胆胰转流术(biliopancreatic diversion，BPD) 腹腔镜可调节胃捆绑术(laparoscopic adjustable gastric banding，LAGB) 胃空肠旁路术(gastrojejunal bypass，GJB) 垂直捆绑胃成形术(vertical banded gastroplasty，VBG) 十二指肠空肠旁路术(duodenal-jejunal bypass，DJB) 空肠回肠旁路术（Jejunoileal Bypass，JIB),Roux-en-Y胃旁路术（RYGB）,Roux-en-Y gastric bypass (RYGB）,Roux-en-Y胃旁路术（RYGB）,Whitson et al. reported that there was no change in GIP levels 6 months postoperatively in both diabetic and non-diabetic patients after RYGB. Rubino et al. found that fasting GIP levels were reduced after RYGB only in diabetics but not in non-diabetics. Laferrere et al. found that meal stimulated GIP levels were found to be increased 1.5 times after RYGB . 结论：在大多数研究报告中，餐后GIP含量降低；在一些研究报告中，空腹GIP含量降低。,胆胰转流术（BPD）,手术方法：切断胃后，于Trietz氏韧带下约50 cm处分离、切断空肠，空肠远端与胃近端吻合;近端空肠端侧吻合于距回盲瓣50 cm处。,胆胰转流术（BPD）,Guidone et al. found both fasting and postprandial GIP significantly reduced 1 and 4 weeks after BPD. Mingrone et al. reported that BPD caused a significant decrease in area under the curve (AUC) for GIP and this was more so in diabetic subjects. Salinari et al. found that area under the curve for GIP was decreased by fourfold 1 month after BPD in diabetic patients. 结论:目前实验结果表明,与RYGB手术相比，BPD手术之后GIP降低更加具有统一性。,腹腔镜可调节胃捆绑术(LAGB),结果：可以随时随意调节胃容量的 ，是进入体内的食物量减少,方法：可调节的硅胶带环形捆绑胃中上部，硅胶带的一端自腹部引出体外，可用于术后手动调节,腹腔镜可调节胃捆绑术(LAGB),Shak et al. showed that GIP was unchanged after LAGB at 6 and 12 months post surgery. In the study by Korner et al., the AUC for GIP (fasting to 180 min after meal) was greater than that for RYGB and this was statistically significant. 结论：目前研究结果说明LAGB手术不会导致GIP的降低。,十二指肠空肠旁路术（DJB）,结果： DJB后，食物不经过十二指肠和空肠上段,方法：离断十二直肠起始部和上端空肠，将空肠远侧断端与十二指肠近端端吻合。,十二指肠空肠旁路术（DJB）,Cohen et al. reported that DJB in non-morbidly obese diabetic humans was safe and effective in causing resolution of diabetes . Lee et al. reported there was no change in the AUC of total GIP. 结论:尽管需要进一步的研究，但由此也可以推断GIP可能不是前肠理论的中介物。,Jejunoileal Bypass(JIB),方法：将空肠近端与回肠远端部分吻合，,结果：JIB后，食物绕过小肠营营养吸收段。,Jejunoileal Bypass(JIB),Naslund et al. reported that elevation of GIPmore in the 20-year group after JIB. Ockander et al. reported that Increased density of GIP cells in JIB group. 结论：上述研究发现JIP手术后患者GIP的含量没有降低。,综述结论,GIP是一个肠降糖激素，与肥胖症和T2DM有密切联系。它在肥胖者和葡萄糖不耐者体内含量升高。减重手术后，大部分的人类研究报告指出人体内GIP含量减低。患者体内过高的GIP具有胰岛素抵抗，它的降低对肥胖者和T2DM患者是有益的。所以在治疗肥胖型糖尿病时，GIP拮抗剂可能更有用。故研究GIP拮抗剂，也为治疗肥胖型糖尿病开辟了一条新的道路。,thank you!,