【關(guān)鍵詞】 胃腸手術(shù);糖尿病
糖尿病(diabetes mellitus,DM)是一種嚴(yán)重危害人類健康的慢性代謝性疾病,久病可引起多系統(tǒng)功能損害,且發(fā)病率逐年上升,其中2型糖尿病占90%以上,內(nèi)科并無(wú)性療法,多需要終身服藥維持,嚴(yán)重影響患者的生活、工作。國(guó)外一些學(xué)者在應(yīng)用減肥手術(shù)治療病態(tài)肥胖癥時(shí)偶然發(fā)現(xiàn)合并2型糖尿病的患者術(shù)后血糖竟然得到了很好的控制,且并不需口服藥物和飲食調(diào)節(jié),之后大量的研究發(fā)現(xiàn)減肥手術(shù)對(duì)2型糖尿病的確有著神奇的療效,其中以 Roux-Y 胃旁路手術(shù)(Roux-Y grastric bypass,GBP)效果好且相對(duì)安全[1],目前在我國(guó)GBP也開(kāi)始廣發(fā)應(yīng)用于肥胖合并2型糖尿病的治療,對(duì)于非肥胖的T2DM患者是否適用此術(shù)式還在進(jìn)一步的研究中,這無(wú)疑是給廣大T2DM患者帶來(lái)了新的希望,下面本文就將GBP治療T2DM的進(jìn)展情況做一綜述。
1 GBP 治療T2DM的歷史沿革
1987年P(guān)ories等[2]報(bào)道3例肥胖癥合并T2DM且伴有嚴(yán)重并發(fā)癥患者施行GBP后,患者血糖在不需任何藥物及飲食調(diào)節(jié)的情況下水平顯著下降,且能維持穩(wěn)定。1995年P(guān)ories等[3]又對(duì)146例肥胖合并T2DM患者施行GBP 術(shù)后進(jìn)行長(zhǎng)達(dá)14年的隨訪,發(fā)現(xiàn)有121例T2DM得到治愈。之后大量研究證實(shí)肥胖癥并發(fā)T2DM施行GBP手術(shù)后能長(zhǎng)期治愈T2DM[4~6],且研究發(fā)現(xiàn)GBP對(duì)體重正常的T2DM患者也有很好的療效[7]。GBP治療T2DM受到世界性的廣泛關(guān)注,其臨床療效也得到充分肯定[8,9]。
2 GBP 的手術(shù)方法
切斷并閉合胃遠(yuǎn)端大部,在距十二指腸懸韌帶30~50cm處切斷空腸,遠(yuǎn)端與殘胃大彎處吻合,近端空腸吻合于距胃-空腸吻合口50~150cm處空腸,形成Roux-en-Y胃旁路術(shù)(GBP)。此術(shù)式使食物不經(jīng)過(guò)胃遠(yuǎn)端、十二指腸和近段空腸,并將消化道分為兩個(gè)區(qū)域:①食物轉(zhuǎn)流區(qū);②食物流經(jīng)區(qū)。近年腔鏡下GBP已廣泛開(kāi)展,其較開(kāi)腹手術(shù)并發(fā)癥明顯減少,且恢復(fù)更快,現(xiàn)已逐漸取代了傳統(tǒng)的開(kāi)腹手術(shù)成為目前主要術(shù)式[10]。
3 GBP 治療T2DM的作用機(jī)制
GBP治療T2DM的機(jī)制尚未明確,目前腸-胰島軸學(xué)說(shuō)得到廣泛認(rèn)同,認(rèn)為與胃轉(zhuǎn)流術(shù)后胃腸激素變化密切相關(guān)[11],研究的重點(diǎn)集中在糖依賴性胰島素釋放肽(GIP)、胰高血糖素樣肽-1(GLP-1)、胰島素樣生長(zhǎng)因子-1(IGF-1)、瘦素(Leptin)、脂連素(adiponectin)、生長(zhǎng)激素釋放肽(Ghrelin)、二肽基肽酶-Ⅳ(DPP-Ⅳ)、肽YY(PYY)等[12~14]。GBP通過(guò)胃腸道重組,將胃腸道分為食物轉(zhuǎn)流區(qū)和流經(jīng)區(qū)兩個(gè)區(qū)域,這將引起胃腸激素的變化,具體分為兩個(gè)方面:①GBP后食物不經(jīng)過(guò)遠(yuǎn)段胃、十二指腸和近段空腸,引起某種胃腸激素分泌減少,從而減輕胰島素抵抗,增強(qiáng)胰島素敏感性,抑制胰島細(xì)胞凋亡,促進(jìn)胰島細(xì)胞增生,從根本上治愈T2DM[15];②GBP后未消化食物過(guò)早到達(dá)遠(yuǎn)段空腸、回腸及結(jié)腸,刺激此段腸道引起某種激素的分泌增加,從而促進(jìn)胰島素合成,促進(jìn)胰島B細(xì)胞增生和抑制凋亡,達(dá)到長(zhǎng)期治愈T2DM[16]。當(dāng)然,還可能存在其他假說(shuō),如葡萄糖毒性學(xué)說(shuō)、炎性介質(zhì)假說(shuō)、異常信號(hào)機(jī)制學(xué)說(shuō)、神經(jīng)內(nèi)分泌學(xué)說(shuō)等,有待進(jìn)一步深入研究。
4 GBP治療T2DM的可行性
GBP預(yù)防和治療T2DM優(yōu)勢(shì)顯著,對(duì)于肥胖癥患者,GBP不僅可以減重,而且還能阻止這類T2DM發(fā)病高危人群的發(fā)病;對(duì)于肥胖癥伴T(mén)2DM的患者,GBP則更顯示出一箭雙雕的神奇療效;對(duì)于非肥胖的T2DM患者是否適用GBP還需臨床進(jìn)一步論證,有待長(zhǎng)期的臨床觀察,且需制定嚴(yán)格、詳細(xì)的手術(shù)指證?,F(xiàn)已明確,肥胖癥合并T2DM的患者是GBP的適應(yīng)證,且術(shù)前患者血清胰島素和C肽值升高或正常才適合做GBP,若降低,常提示胰島功能不全或衰竭,為GBP治療T2DM的禁忌證,當(dāng)然術(shù)前也要評(píng)估心肺腎等重要臟器功能,以排除其他手術(shù)禁忌證。手術(shù)并發(fā)癥包括吻合口漏、吻合口潰瘍、狹窄、胃腸道及重要臟器副損傷、胃腸道出血、腹腔感染、腹腔膿腫形成、切口感染、深靜脈血栓形成、肺栓塞、腸梗阻等,但隨著手術(shù)技術(shù)的提高,這些并發(fā)癥已經(jīng)顯著降低。GBP 手術(shù)費(fèi)用相對(duì)低廉,且不需藥物維持和飲食限制,可以減輕患者經(jīng)濟(jì)負(fù)擔(dān),提高患者生活質(zhì)量。大量臨床實(shí)踐證實(shí),GBP治療T2DM是可行的[17]。
5 結(jié)語(yǔ)
GBP 作T2DM的一種新的、有效可行的治療方法 ,有著明顯的優(yōu)勢(shì),隨著微創(chuàng)技術(shù)的不斷發(fā)展和廣泛應(yīng)用,現(xiàn)腹腔鏡下GBP已在臨床上廣泛開(kāi)展,為廣大T2DM患者帶來(lái)了希望。 雖然GBP治療T2DM的機(jī)制尚未明確,但我們相信隨著基礎(chǔ)和臨床研究的不斷深入,必將為T(mén)2DM的外科治療開(kāi)辟一個(gè)嶄新的領(lǐng)域,造福更多的患者。
【參考文獻(xiàn)】
[1] White S,Brooks E,Jurikova L,et al. Long-term outcomes after gastric bypass[J].Obes Surg,2005,15(2):155163
[2] Pories WJ,Caro JF,F(xiàn)lickinger EG,et al. The control of diabetes mellitus( NIDDM) in the morbidly obese with the greenville gastric bypass[J]. Ann Surg,1987,206(3):316323
[3] Pories WJ, Swanson MS, Mac Donald KG, et al. Who would have thought it? An operation roves to be the most effective therapy for adult -onset diabetes mellitus[J]. Ann Surg,1995,22(2):339350
[4] Arterburn D, Schauer DP, Wise BE, et al. Change in predicted 10-year cardiovascular risk following laparoscopic Roux-en-Y gastric bypass surgery[J]. Obes Surg, 2009,19(2):184189
[5] Flum DR, Belle SH, King WC, et al. Perioperative safety in the longitudinal assessment of bariatric surgery[J]. N Engl J Med,2009, 361(5):445454
[6] Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and me[x]ta-analysis[J]. Am J Med, 2009, 122(3): 248256
[7] Cohen RV, Schiavon CA, Pinheiro JS, et al. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases[J]. Surg Obes Relat Dis, 2007, 3(2):195197
[8] Lima MM,Pareja JC,Alegre SM,et al. Acute effect of roux-en-y gastric bypass on whole-body insulin sensitivity: a study with the euglycemic-hyperinsulinemic clamp[J]. J Clin Endocrinol me[x]tab,2010,95(8):38713875
[9] Kashyap SR,Daud S,Kelly KR,et al. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes[J].Int J Obes( Lond) ,2010,34(3):462471
[10] Peifer KJ, Shiels AJ, Azar R, et al. Successful endoscopic management of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass[ J].Gastrointest Endoscop,2007,66(2):248252
[11] Pories WJ,Albrecht RJ. Etiology of type 2 diabetes mellitus:role of the foregut [J].World J Surg,2001,25(4):527531
[12] 王躍生,史逸華,陳福軍. 胃轉(zhuǎn)流術(shù)對(duì)2型糖尿病大鼠空腹血糖的影響及其機(jī)理[J]. 中國(guó)普外基礎(chǔ)與臨床雜志,2011,18(8):849853
[13] Pacheco D,Luis D A, Romero A, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose me[x]tabolism in Goto-Kakizaki rats[J]. Am J Surg,2007,194(2):221224
[14] Carel WR, Simon JBA,Rachel LB, et al.Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss,and improve me[x]tabolic parameters[J]. Ann Surg, 2006, 243 (1):108114
[15] Rubino F,F(xiàn)orgione A,Cummings DE,et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes[J]. Ann Surg,2006, 244(5):741749
[16] Vilsbill T,Zdravkovic M,Le-Thi T,et al. Liraglutide,a long-acting human glucagon-like peptide-1 analog,given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes[J].Diabetes Care,2007,30(6): 16081610
[17] Bevilacqua M,Dominguez LJ,Righini V,et al. Acute parathyroid hormone increase by oral peptones administration after roux-en-Y gastric bypass surgery in obese subjects: role of phosphate in the rapid control of parathyroid hormone release[J].Surgery,2010,147(5):655661