1、GIP and Bariatric Surgery,Contents,背景介紹,GIP相關(guān)知識(shí),減重手術(shù),綜述結(jié)論,5,2,3,4,1,背景知識(shí),治療T2DM的兩種理論,背景介紹,減重手術(shù)(Bariatric Surgery)是目前治療病態(tài)肥胖癥最有效的治療方法,同時(shí)可以治療肥胖合并癥如2型糖尿?。═2DM）、高血壓、高血脂等。但目前減重手術(shù)減肥和治療T2DM的治病機(jī)理存在爭議。傳統(tǒng)認(rèn)為減重手術(shù)阻礙食物吸收和引起消化不良是減肥和改善T2DM的唯一治療機(jī)制?，F(xiàn)在發(fā)現(xiàn)Bariatric Surgery之后改變了一些胃腸激素的分泌和作用，減輕體內(nèi)胰島素抵抗而起治療作用。其中GIP的生理作用及手術(shù)后的

2、改變備受爭議。,GIP相關(guān)知識(shí),GIP在人體中的生理作用,GIP在肥胖者和T2DM體內(nèi)的作用,GIP和GLP-1的不同,減重手術(shù)如何引起GIP的改變,GIP在人體中的生理作用,GIP主要由分布于十二指腸和空腸的k細(xì)胞分泌，在健康人體中主要有以下生理作用： 1、GIP是一個(gè)生理性腸降血糖素，有葡萄糖依賴的促胰島素分泌作用； 2、GIP能引起餐后胰高血糖素的升高； 3、GIP能預(yù)防胰島細(xì)胞的凋亡和促進(jìn)胰島細(xì)胞的增殖； 4、GIP能促進(jìn)葡萄糖的吸收、葡萄糖轉(zhuǎn)化為脂肪酸及脂肪在脂肪組織的沉積； 5、GIP妨礙骨質(zhì)吸收，促進(jìn)骨的形成； 6、GIP對(duì)人體胃能動(dòng)性作用小。,GIP和GLP-1的不同,GIP在

3、肥胖者和T2DM體內(nèi)的作用,The cause of this GIP resistance is down -regulation（下調(diào)）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

4、 GIP producing K cells in the duodenum.,GIP在肥胖者和T2DM體內(nèi)的作用,GIP在肥胖者和T2DM體內(nèi)的作用,結(jié)論： GIP在肥胖者和T2DM體內(nèi)含量增加，這導(dǎo)致胰島素抵抗和葡萄糖依賴胰島素分泌功能受損。因此降低患者體內(nèi)GIP含量可用來治療肥胖型T2DM.,減重手術(shù)如何引起GIP的改變,減重手術(shù)如何引起GIP的改變,In a study by Rudnicki et al. on rats, it was found that the presence of food and bile（膽汁） is necessary for the secretio

5、n 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. 結(jié)論：減重手術(shù)改變了食物的流向，使十二直腸和空腸處的k細(xì)胞營養(yǎng)缺乏，因此導(dǎo)致k細(xì)胞分泌GIP的量減少。,治療T2DM的理論,后腸道理論 （The hindgut theory）,腸道理論,前腸道理論 （The foregut theory）,后腸道理論 （The h

6、indgut theory）,減重手術(shù)使食物提前進(jìn)入回腸，食物刺激誘導(dǎo)后腸激素分泌，這種激素被認(rèn)為是GLP-1 ，它可以調(diào)控胰島內(nèi)分泌功能，增加胰島素的合成和/或釋放，改善外周組織對(duì)胰島素敏感性，從而達(dá)到控制糖尿病的作用 。,前腸道理論 （The foregut theory）,手術(shù)前，糖尿病易感者的上消化道經(jīng)食物刺激產(chǎn)生“胰島素抵抗因子”，使人體產(chǎn)生胰島素抵抗現(xiàn)象。手術(shù)后，營養(yǎng)物質(zhì)避開對(duì)胃十二指腸的刺激，減少“胰島素抵抗因子”等物質(zhì)的釋放，導(dǎo)致2型糖尿病的胰島素拮抗減輕或消失。研究認(rèn)為這種胰島素抵抗因子對(duì)抗GIP作用。,兩種理論的爭議,Wang et al. showed in an exp

7、eriment 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. 結(jié)論：研究發(fā)現(xiàn)兩種理論可能都成立，減肥手術(shù)中它們共同起作用。,減重手術(shù),Roux-en-Y胃旁路術(shù)( Roux-en-Y gastric bypass RYGB) 膽胰

8、轉(zhuǎn)流術(shù)(biliopancreaticdiversion，BPD) 腹腔鏡可調(diào)節(jié)胃捆綁術(shù)(laparoscopicadjustablegastricbanding，LAGB) 胃空腸旁路術(shù)(gastrojejunalbypass，GJB) 垂直捆綁胃成形術(shù)(verticalbandedgastroplasty，VBG) 十二指腸空腸旁路術(shù)(duodenal-jejunalbypass，DJB) 空腸回腸旁路術(shù)（Jejunoileal Bypass，JIB),Roux-en-Y胃旁路術(shù)（RYGB）,Roux-en-Y gastric bypass (RYGB）,Roux-en-Y胃旁路術(shù)（RYG

9、B）,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 stimulate

10、d GIP levels were found to be increased 1.5 times after RYGB . 結(jié)論：在大多數(shù)研究報(bào)告中，餐后GIP含量降低；在一些研究報(bào)告中，空腹GIP含量降低。,膽胰轉(zhuǎn)流術(shù)（BPD）,手術(shù)方法：切斷胃后，于Trietz氏韌帶下約50cm處分離、切斷空腸，空腸遠(yuǎn)端與胃近端吻合;近端空腸端側(cè)吻合于距回盲瓣50cm處。,膽胰轉(zhuǎn)流術(shù)（BPD）,Guidone et al. found both fasting and postprandial GIP significantly reduced 1 and 4 weeks after BPD. Ming

11、rone 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. 結(jié)論:目前實(shí)驗(yàn)結(jié)果表明,與RYGB手術(shù)相比，BPD手術(shù)之后GIP降低更加具

12、有統(tǒng)一性。,腹腔鏡可調(diào)節(jié)胃捆綁術(shù)(LAGB),結(jié)果：可以隨時(shí)隨意調(diào)節(jié)胃容量的 ，是進(jìn)入體內(nèi)的食物量減少,方法：可調(diào)節(jié)的硅膠帶環(huán)形捆綁胃中上部，硅膠帶的一端自腹部引出體外，可用于術(shù)后手動(dòng)調(diào)節(jié),腹腔鏡可調(diào)節(jié)胃捆綁術(shù)(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 f

13、or RYGB and this was statistically significant. 結(jié)論：目前研究結(jié)果說明LAGB手術(shù)不會(huì)導(dǎo)致GIP的降低。,十二指腸空腸旁路術(shù)（DJB）,結(jié)果： DJB后，食物不經(jīng)過十二指腸和空腸上段,方法：離斷十二直腸起始部和上端空腸，將空腸遠(yuǎn)側(cè)斷端與十二指腸近端端吻合。,十二指腸空腸旁路術(shù)（DJB）,Cohen et al. reported that DJB in non-morbidly obese diabetic humans was safe and effective in causing resolution of diabetes . Lee

14、et al. reported there was no change in the AUC of total GIP. 結(jié)論:盡管需要進(jìn)一步的研究，但由此也可以推斷GIP可能不是前腸理論的中介物。,Jejunoileal Bypass(JIB),方法：將空腸近端與回腸遠(yuǎn)端部分吻合，,結(jié)果：JIB后，食物繞過小腸營營養(yǎng)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 JI