黃致錕
臺(tái)灣義大醫(yī)院國(guó)際減重及糖尿病手術(shù)中心 國(guó)際微創(chuàng)手術(shù)訓(xùn)練中心 臺(tái)灣減重支持教育協(xié)會(huì),臺(tái)灣高雄 824
·減重、糖尿病手術(shù)及綜合治療論壇論著·
腹腔鏡下Roux-en-Y胃旁路術(shù)在非病態(tài)肥胖患者2型糖尿病治療中的應(yīng)用價(jià)值
黃致錕
臺(tái)灣義大醫(yī)院國(guó)際減重及糖尿病手術(shù)中心 國(guó)際微創(chuàng)手術(shù)訓(xùn)練中心 臺(tái)灣減重支持教育協(xié)會(huì),臺(tái)灣高雄 824
目的探討腹腔鏡下Roux-en-Y胃旁路術(shù)(LRYGB)在非病態(tài)肥胖患者2型糖尿病治療中的應(yīng)用價(jià)值。方法以22例體重指數(shù)(BMI)介于25~35 kg/m2間的非病態(tài)肥胖2型糖尿病患者為研究對(duì)象,行LRYGB,觀察手術(shù)前后BMI、空腹血糖和糖化血紅蛋白的變化情況,分析與手術(shù)預(yù)后相關(guān)的因素。結(jié)果22例患者均成功接受LRYGB,并完成術(shù)后12個(gè)月的隨訪。2例(9.1%)患者術(shù)后出現(xiàn)并發(fā)癥,其中1例早期出現(xiàn)胃空腸吻合口出血,1例因發(fā)生腹瀉需要重建腸繞道長(zhǎng)度。術(shù)后第12個(gè)月,14例(63.6%)患者達(dá)到糖尿病治愈,6例(27.3%)血糖得到控制,2例(9.1%)血糖得到改善。與血糖控制或改善組患者相比,糖尿病治愈組患者手術(shù)前的BMI較高(P=0.001)、年齡較輕(P=0.002)、糖尿病病程較短(P=0.001)。結(jié)論LRYGB可安全有效地治療非病態(tài)肥胖2型糖尿病患者,此類患者早期行LRYGB干預(yù)可能效果更佳。
腹腔鏡下Roux-en-Y胃旁路術(shù);2型糖尿病;非病態(tài)肥胖
糖尿病是慢性進(jìn)展性疾病,也是一種常見的內(nèi)分泌疾病,根據(jù)世界衛(wèi)生組織的統(tǒng)計(jì),到2025年,全世界糖尿病患病人數(shù)將達(dá)到3.34億[1]。2型糖尿病的內(nèi)科治療方法主要包括:飲食、運(yùn)動(dòng)和抗糖尿病藥物治療。然而不斷有證據(jù)顯示,外科手術(shù)可完全治愈2型糖尿病,特別是病態(tài)肥胖的2型糖尿病患者[2]。目前,包括腹腔鏡下Roux-en-Y胃旁路術(shù)(laparoscopic Roux-en-Y gastric bypass, LRYGB)在內(nèi)的減重手術(shù)在緩解2型糖尿病方面的療效已經(jīng)得到證實(shí)[3-5]。但很少有證據(jù)證明LRYGB治療較低體重指數(shù)(body mass index,BMI)的2型糖尿病患者的效果[6]。本研究評(píng)估了LRYGB在非病態(tài)肥胖患者2型糖尿病治療中的應(yīng)用價(jià)值,以期為今后的臨床應(yīng)用提供幫助。
對(duì)象2008年12月至2010年1月在臺(tái)灣義大醫(yī)院接受LRYGB的非病態(tài)肥胖2型糖尿病患者22例,其中,男2例,女20例,平均年齡(47.4±11.2)歲(28~63歲);平均BMI(30.8±3.2)kg/m2(25.0~34.8 kg/m2),其中10例(45.5%)25.0 kg/m2≤BMI﹤30.0 kg/m2,12例(54.5%)30.0 kg/m2≤BMI﹤35.0 kg/m2;平均患病時(shí)間為(6.57±6.34)年(1~20年)。2型糖尿病診斷參照美國(guó)糖尿病協(xié)會(huì)(American Diabetes Association,ADA)制訂的標(biāo)準(zhǔn)或被內(nèi)分泌專家或糖尿病專家認(rèn)定有效[7]。入選標(biāo)準(zhǔn):(1)年齡18~65歲;(2)25.0 kg/m2≤BMI﹤35.0 kg/m2;(3)糖化血紅蛋白(glycosylated hemoglobin,HbAlc)≥7%。排除標(biāo)準(zhǔn):(1)年齡﹤18歲或﹥65歲;(2)計(jì)劃在2年內(nèi)懷孕;(3)消化道炎性疾病患者;(4)惡性腫瘤患者;(5)未解決的精神疾病或者濫用藥物者。22例患者中,16例(72.7%)有2型糖尿病家族史;15例(68.2%)術(shù)前服用口服降糖藥,1例(4.5%)需要胰島素治療,3例(13.6%)同時(shí)使用胰島素和口服降糖藥,3例(13.6%)無(wú)原因中止服用藥物;15例(68.2%)有多種合并癥;14例(63.6%)有高脂血癥,13例(59.1%)有高血壓,10例(45.5%)有脂肪肝,2例(9.1%)有痛風(fēng)性關(guān)節(jié)炎。本研究經(jīng)臺(tái)灣義大醫(yī)院倫理委員會(huì)批準(zhǔn)(EMRP-097-106),所有患者在了解2型糖尿病現(xiàn)有治療規(guī)程和術(shù)中、術(shù)后的風(fēng)險(xiǎn)、益處后簽署了知情同意書。
術(shù)前準(zhǔn)備所有患者術(shù)前必須接受專業(yè)的多學(xué)科醫(yī)療團(tuán)隊(duì)評(píng)估,包括:外科醫(yī)師、內(nèi)分泌醫(yī)師、麻醉醫(yī)師、營(yíng)養(yǎng)師及其他與糖尿病并發(fā)癥相關(guān)的內(nèi)科疾病專家。除進(jìn)行具體的糖尿病指標(biāo)檢查外,還要進(jìn)行常規(guī)的術(shù)前檢查和心理測(cè)量與輔導(dǎo)。
手術(shù)方法參照文獻(xiàn)[8]的方法(圖1),其中小胃囊的容量只保留30 ml, 膽胰肢(bilio-pancreatic limb)與消化肢(alimentary limb)各繞道100 cm長(zhǎng)度。
圖 1 腹腔鏡下Roux-en-Y胃旁路術(shù)手術(shù)圖解Fig 1 Surgical method of laparoscopic Roux-en-Y gastric bypass
數(shù)據(jù)收集
術(shù)前:(1)BMI;(2)合并癥;(3)罹患糖尿病的具體細(xì)節(jié),包括:疾病持續(xù)時(shí)間、家族史和藥物使用情況;(4)空腹血糖(fasting blood glucose,F(xiàn)BG);(5)HbAlc。
手術(shù)細(xì)節(jié):手術(shù)時(shí)間、住院時(shí)間及至下次隨訪前的并發(fā)癥。
術(shù)后:于術(shù)后1周,1、3、6、9、12個(gè)月進(jìn)行隨訪,記錄患者的FBG、HbAlc、BMI和藥物使用情況。
療效判定參照ADA制定的標(biāo)準(zhǔn):(1)治愈:患者沒有服用抗糖尿病藥物,F(xiàn)BG <5.55 mmol/L(100 mg/dl),HbAlc<6%;(2)血糖得到控制:沒有服用抗糖尿病藥物且HbAlc≤7%;(3)改善:FBG降低幅度大于1.39 mmol/L(25 mg/dl),HbAlc降低幅度大于1%;(4)失?。貉侵笖?shù)沒有明顯改善或者加重,患者使用的抗糖尿病藥物劑量增加[9]。
統(tǒng)計(jì)學(xué)處理采用SPSS 15.0統(tǒng)計(jì)軟件,計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示,計(jì)數(shù)資料以百分率表示;計(jì)量資料組內(nèi)不同時(shí)間的比較采用配對(duì)t檢驗(yàn),組間比較采用獨(dú)立樣本t檢驗(yàn);計(jì)數(shù)資料組間比較采用Fisher’s 確切檢驗(yàn);P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
手術(shù)情況所有患者均成功接受LRYGB,平均手術(shù)時(shí)間(72.8±18.2)min(45~134min),平均住院時(shí)間(2.41±0.73)d(2~4d)。22例患者中,無(wú)1例死亡。2例(9.1%)出現(xiàn)并發(fā)癥,其中1例早期發(fā)生胃腸吻合口出血,以胃鏡成功治愈;1例出現(xiàn)頻繁稀便,行二次腹腔鏡手術(shù)重建腸繞道長(zhǎng)度予以糾正。
BMI、FBG和HbAlc的變化情況所有患者均完成術(shù)后12個(gè)月的隨訪,術(shù)后6、9、12個(gè)月的BMI(P均<0.001)、FBG(P均=0.001)和HbAlc水平(P均<0.001)均較術(shù)前明顯降低(表1)。
預(yù)后及相關(guān)因素分析22例患者中,有7例(31.8%)在術(shù)后1個(gè)月內(nèi)FBG恢復(fù)正常,14例(63.6%)術(shù)后6個(gè)月內(nèi)HbAlc恢復(fù)正常。術(shù)后第12個(gè)月,14例(63.6%)患者的2型糖尿病治愈,6例(27.3%)患者的血糖得到控制,2例(9.1%)患者的血糖得到改善。20例(90.9%)患者不再需要服用藥物;2例(9.1%)仍需口服降糖藥物, 這兩例患者術(shù)前均需口服降糖藥和胰島素并用。與血糖控制或改善組患者相比,糖尿病治愈組患者手術(shù)前的BMI較高(P=0.001)、年齡較輕(P=0.002)、糖尿病病程較短(P=0.001)(表2)。
糖尿病是由于胰島素分泌或(和)作用缺陷導(dǎo)致的以高血糖為特征的一組慢性進(jìn)展性代謝性疾病[10]。在糖尿病的臨床類型中,2型糖尿病是最普遍的一種。2型糖尿病內(nèi)科治療的主要目的是控制血糖以降低并發(fā)癥,而外科手術(shù)則有望使血糖達(dá)到永久正常[11]。 Buchwald等[5]總結(jié)了3188例病態(tài)肥胖患者的手術(shù)效果,結(jié)果顯示:95.1%的患者在行膽胰曠置術(shù)后,80.3%的患者在行LRYGB后,56.7%的患者在行腹腔鏡下可調(diào)節(jié)胃束帶術(shù)后糖尿病得到緩解。目前的研究則開始集中對(duì)在1991年美國(guó)國(guó)立衛(wèi)生研究院指南(BMI<35 kg/m2) 范圍之外患者進(jìn)行手術(shù)的作用[12]。
表 1 BMI、FBG和HbAlc的變化情況
BMI:體重指數(shù);FBG:空腹血糖;HbAlc:糖化血紅蛋白;與術(shù)前比較,aP<0.001,bP=0.001
BMI: body mass index;FBG:fasting blood glucose;HbAlc:glycosylated hemoglobin;aP<0.001,bP=0.001 compared with pre-operative levels
表 2 預(yù)后相關(guān)因素分析
TC:總膽固醇;TG:三酰甘油;HDL-C:高密度脂蛋白膽固醇;LDL-C:低密度脂蛋白膽固醇
TC:total cholesterol;TG:triglyceride;HDL-C:high density lipoprotein cholesterol;LDL-C:low density lipoprotein cholesterol
自從1955年Friedman等[13]首次報(bào)道胃次全切除可改善糖尿病后,已有大量研究證實(shí)手術(shù)對(duì)糖尿病的治療效果[13-18]。盡管術(shù)后糖尿病得到治愈的確切機(jī)制尚不十分清楚,但是以已了解機(jī)制為基礎(chǔ)的各項(xiàng)創(chuàng)新性手術(shù),如:十二指腸空腸旁路術(shù)、袖狀胃切除合并回腸間置術(shù)已試用于臨床[19-22]。已提出的機(jī)制包括:手術(shù)后造成飲食攝取減少、體重下降、脂肪組織減少;十二指腸隔絕與繞道,腸胃改道引起的腸胃激素水平變化;吸收不良。因此,本研究選擇術(shù)式的標(biāo)準(zhǔn)是可以影響并改善上述機(jī)制,如胃或膽胰旁路手術(shù)。目前LRYGB治療病態(tài)肥胖患者2型糖尿病的效果已經(jīng)得到肯定[23],筆者所在的團(tuán)隊(duì)也已采用LRYGB治療了500多例患者,無(wú)1例死亡發(fā)生,且近來(lái)研究也證實(shí)該術(shù)式極具可行性[16,24-25],故本研究選擇采用LRYGB治療非病態(tài)肥胖2型糖尿病患者,結(jié)果顯示:所有患者均成功接受了手術(shù),無(wú)1例患者死亡,僅2例(9.1%)患者出現(xiàn)并發(fā)癥,與Lee等[26](6.2%的患者出現(xiàn)較小的并發(fā)癥,2.2%的患者出現(xiàn)較大的并發(fā)癥)和 Fried 等[27](并發(fā)癥發(fā)生率為10.3%)的研究結(jié)果類似。雖然這些并發(fā)癥都容易處理并有因可循,但筆者建議在患者選擇過程中應(yīng)謹(jǐn)慎考慮與評(píng)估2型糖尿病本身的并發(fā)癥。
有研究認(rèn)為,在病態(tài)肥胖患者減重手術(shù)后由于胰島素耐性改變,F(xiàn)BG在數(shù)天內(nèi)會(huì)恢復(fù)正常[28]。本研究顯示,患者術(shù)后FBG雖然有所改善,但并未馬上恢復(fù)到正常,F(xiàn)BG和HbAlc水平隨著時(shí)間推移逐漸減低,2例患者在術(shù)后1周、7例在術(shù)后1個(gè)月、14例在術(shù)后6個(gè)月恢復(fù)正常。此外本研究還發(fā)現(xiàn),那些在術(shù)后6個(gè)月仍未能治愈的患者在術(shù)后12個(gè)月同樣沒有治愈,且此類患者在術(shù)后6個(gè)月體重就接近穩(wěn)定,提示胰島素抵抗消失后,胰島功能在某些患者并未完全改善,推測(cè)這些患者除了胰島素抵抗之外,可能還存在胰島素缺乏。
Lee等[26]研究顯示,76.5% BMI<35 kg/m2的患者在術(shù)后1年可達(dá)到2型糖尿病治療的ADA目標(biāo)。Hall等[29]報(bào)道68.4%的患者在LRYGB術(shù)后停止使用所有治療糖尿病的藥物。本研究22例患者中,術(shù)后只有2例還在使用低劑量口服降糖藥,沒有患者使用胰島素,治愈率和血糖控制率達(dá)到90.9%。
對(duì)預(yù)后及相關(guān)因素的分析發(fā)現(xiàn),手術(shù)前BMI較低、年齡較大、糖尿病持續(xù)時(shí)間較長(zhǎng)的患者在術(shù)后12個(gè)月治愈的可能性較小,與Hall等[29]研究結(jié)果類似,提示對(duì)較肥胖的糖尿病患者,應(yīng)盡早進(jìn)行手術(shù)干預(yù),但對(duì)體重較輕的患者,尚需更多資料來(lái)證明手術(shù)是否有效。
綜上,本研究結(jié)果顯示,對(duì)BMI介于25~35 kg/m2之間的患者實(shí)施LRYGB是安全可行的,且早期并發(fā)癥發(fā)生率較低。年齡、BMI和2型糖尿病的持續(xù)時(shí)間與預(yù)后有關(guān),BMI較高的患者早期行LRYGB干預(yù)可能效果更佳。
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[18] Parikh M, Duncombe J, Fielding GA. Laparoscopic adjustable gastric banding for patients with body mass index of [19] Scopinaro N, Papadia F, Marinari G, et al. Long-term control of type 2 diabetes mellitus and the other major components of the metabolic syndrome after biliopancreatic diversion in patients with BMI<35 kg/m2[J]. Obes Surg, 2007, 17(2):185-192. [20] Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals role of the proximal small intestine in the pathophysiology of type 2 diabetes[J]. Ann Surg, 2006, 244(5):741-749. [21] 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):195-197. [22] DePaula AL, Macedo AL, Mota BR, et al. Laparoscopic ileal interposition associated to a diverted sleeve gastrectomy is an effective operation for the treatment of type 2 diabetes mellitus patients with BMI 21-29[J]. Surg Endosc, 2009, 23(6):1313-1320. [23] DePaula AL, Macedo AL, Schraibman V, et al. Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20-34[J]. Surg Endosc, 2009, 23(8):1724-1732. [24] Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en-Y gastric bypass on type 2 diabetes mellitus[J]. Ann Surg, 2003, 238(4):467-485. [25] Cohen R, Pinheiro JS, Correa JL, et al. Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m2: a tailored approach[J]. Surg Obes Relat Dis, 2006, 2(3):401-404. [26] Lee WJ, Wang W, Lee YC, et al. Effect of laparoscopic minigastric bypass for type 2 diabetes mellitus: comparison of BMI > 35 and <35 kg/m2[J]. J Gastrointest Surg, 2008, 12(5):945-952. [27] Fried M, Ribaric G, Buchwald JN, et al. Metabolic surgery for the treatment of type 2 diabetes in patients with BMI < 35kg/m2: an integrative review of early studies[J]. Obes Surg, 2010, 20(6):776-790. [28] Pournaras DJ, Osborne A, Hawkins SC, et al. Remission of type 2 diabetes after gastric bypass and banding: mechanisms and 2 year outcomes[J]. Ann Surg, 2010, 252(6):966-971. [29] Hall TC, Pellen MG, Sedman PC, et al. Preoperative factors predicting remission of type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery for obesity[J]. Obes Surg, 2010, 20(9):1245-1250. EffectivenessandSafetyofLaparoscopicRoux-en-YGastricBypassinTreatingType2DiabetesMellitusinNon-morbidlyObesePatients HUANG Chih-kun Bariatric & Metabolic International Surgery Center, International Minimally Invasive Surgery Training Center, ObjectiveTo evaluate the effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGB) for achieving type 2 diabetes mellitus (T2DM) remission in patients with body mass index (BMI) in the range of 25-35 kg/m2.MethodsTwenty-two non-morbidly obese (BMI: 25-35 kg/m2) patients with T2DM underwent LRYGB. The changes of BMI, fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c) levels were recorded, and the prognostic factors were analyzed.ResultsAll these 22 patients successfully underwent LRYGB and were followed up for twelve months. Two patients (9.1%) developed complications: one patient had an early hemorrhage at the gastrojejunostomy site, and the other had frequent loose stools that required revision surgery. At 12 months, 14 patients (63.6%) showed T2DM remission, 6 (27.3%) showed glycemic control, and 2(9.1%) showed improvement. Compared with the latter two groups, patients in the T2DM remission group had significantly higher BMI (P=0.001), younger age (P=0.002), and shorter duration of diabetes (P=0.001) before operation.ConclusionsLYRGB can efficiently and safely treat T2DM in non-morbidly obese patients. Early intervention in these patients may yield better outcomes. laparoscopic Roux-en-Y gastric bypass; type 2 diabetes mellitus; non-morbid obesity ActaAcadMedSin, 2011,33(3):272-276 電子郵件:dr.ckhuang@hotmail.com R578.1;R656.6+1 A 1000-503X(2011)03-0272-05 10.3881/j.issn.1000-503X.2011.03.013 E-mail: dr.ckhuang@hotmail.com 2011-04-19)
E-Da Hospital, Taiwan Obesity Support Association, Kaohsiung County, Taiwan 824, China