long99 2009-12-18 11:36
提出使用胃腸道手術來治療第2型糖尿病的建議
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
December 1, 2009 — 糖尿病手術高級會議(Diabetes Surgery Summit，DSS)共識研討會回顧相關研究，並做出有關以胃部手術治療第2型糖尿病(type 2 diabetes mellitus，T2DM)的臨床建議。這個新的立場聲明，與臨床及研究議題的建議一致，也與糖尿病手術的整體觀念和定義一致，發表於11月19日線上第一版的外科醫學誌(Annals of Surgery)。
紐約市Weill Cornell醫學院/紐約長老教會醫院的Francesco Rubino醫師和DSS委員寫道，增加胃部手術的證據可以大幅改善第2型糖尿病，不令人意外的，胃腸道手術現在在全球廣被用來治療與肥胖相關的糖尿病，單用於糖尿病也在增加中。不過，手術之於糖尿病治療的角色還未清楚定義，這些實務的指引也不清楚，也沒有足夠的臨床試驗計畫來評估這類糖尿病手術的利益與風險。
【立場聲明的發展】
共識研討會的目標是提出治療第2型糖尿病患的胃腸道手術指引，並發展後續研究計畫。DSS共識文件的目標包括，糖尿病手術的基礎以及學界領袖代表的看法，以證據基礎支持評估更好的手術選項，免於未證實之手術造成的傷害。
在DSS的首次第2型糖尿病胃腸道手術國際研討會中，來自全球各界的50名投票代表委員，於義大利羅馬召開會議，回顧現有的科學證據。由整個小組評估和評論這些資料，以確認證據強度和草擬共識聲明。
會中的草擬聲明，經回顧、辯論、編輯、再評估與正式投票之後發表。總結達到共識的這些聲明之後，交給各投票代表進行後續補充與最後的核准。2008年9月在紐約舉辦的第1屆第2型糖尿病介入性治療世界研討會中，由各界代表回顧與討論最終版的共識聲明， 最後產生現在的立場聲明。
DSS表示，經過仔細挑選的病患，適合以手術方式治療第2型糖尿病。例如，身體質量指數(BMI)大於等於30 kg/m2之糖尿病控制不佳病患，胃繞道手術被視為一個合理的治療選項。
特殊手術包括Roux-en-Y胃繞道手術(Roux-en-Y gastric bypass，RYGB)、腹腔鏡可調式胃束帶手術、膽胰分流術(biliopancreatic diversion)。
DSS建議進行後續臨床試驗，以確認手術對於較不嚴重肥胖和糖尿病患者的精確角色。此外，也迫切需要後續研究探討手術控制糖尿病的潛在機轉，可能有助於闡明糖尿病的病理生理。
【建議】
DSS立場聲明中的特定建議，以及相關證據等級如下：
* BMI≧35 kg/m2、生活型態和藥物治療無法適當控制疾病而適合手術者，適合使用RYGB、腹腔鏡可調式胃束帶手術、膽胰分流術等胃腸道手術，治療其第2型糖尿病(證據等級A)。
* 輕微到中度肥胖(BMI 30 - 35 kg/m2)而適合手術者，那些治療控制不佳第2型糖尿病患的手術方式，可以作為非優先選項(證據等級B)。RYGB可以作為這些病患的糖尿病治療選項(證據等級C)。
* 早期的臨床研究中，新的胃腸道手術技術(例如十二指腸-空腸繞道、迴腸插入、縮胃手術、封閉式袖套手術)顯示對治療第2型糖尿病有效。不過，在目前，它們僅用於人體試驗委員會核准且登記有案的試驗中(證據等級A)。
* 建立標準以測量手術治療第2型糖尿病的臨床與生理結果，是獲得更佳醫療證據的首要之務(證據等級A)。
* 為了評估胃腸道手術治療第2型糖尿病的效益，DSS極力鼓勵進行更多隨機控制試驗(證據等級A)。
* 另一個應優先的重要研究是，確認BMI＜35 kg/m2者使用胃腸道手術治療第2型糖尿病的適當性(證據等級A)。這應和評估胃腸道代謝手術之安全性和效果的臨床控制試驗一起進行(證據等級A)，並確認除了BMI之外可以用來篩選合適病患的其他參數(證據等級A)。
* 發展標準登記/資料庫，將有助於建立BMI＜35 kg/m2者使用胃腸道手術治療第2型糖尿病之適用定義(證據等級A)。
* 動物研究也有助於提供胃腸道代謝手術治療第2型糖尿病的效果與機轉的看法(證據等級A)。
* 胃腸道代謝手術之研究，對探討胃腸道與葡萄糖體內平衡的關聯可提供有價值的、新的機會，用以釐清第2型糖尿病的病理生理機轉(證據等級A)。
* 腹腔鏡可調式胃束帶手術之後，根據現有的動物和臨床研究證據，減重與糖尿病控制有關(證據等級A)。不過，除了關於減少進食和減輕體重的機轉，與RYGB、膽胰分流術、十二指腸-空腸繞道等腸繞道手術有關(證據等級A)。此外，改善第2型糖尿病的確定生理機轉，因為不同胃腸道區域的解剖改變而活化(證據等級B)。
* 為了改善對調整代謝之胃腸道機轉的瞭解，且用以改善第2型糖尿病的治療，應鼓勵內分泌科、外科醫師與基礎科學家合作(證據等級A)。
* 為了監督糖尿病手術的研究與發展，應建立跨部門工作小組，納入內分泌科、外科醫師、臨床與基礎研究者、生物倫理學家以及其他適合的專家(證據等級A)。
DSS之作者們結論表示，代表們一致同意，糖尿病控制不佳且BMI >35 kg/m2的病患，應考量胃腸道手術。這和NIH(國家健康研究中心)指引以及2009美國糖尿病協會照護標準立場聲明一致，且此次進一步強調胃腸道手術對嚴重肥胖病患的角色，如山鐵證顯示手術可改善整體存活。
DSS接受Covidien、Ethicon、Allergan、Storz、GI Dynamics、Roche、Amylin以及Power Medical Interventions等的支持。
Ann Surg. 線上發表於2009年11月19日。
Recommendations Issued for Use of Gastrointestinal Surgery to Treat Type 2 Diabetes
By Laurie Barclay, MD
Medscape Medical News
December 1, 2009 — The Diabetes Surgery Summit (DSS) Consensus Conference reviewed pertinent research and made clinical recommendations regarding gastric surgery as a treatment of type 2 diabetes mellitus (T2DM). The new position statement, which consists of recommendations for clinical and research issues, as well as overall concepts and definitions in diabetes surgery, is published in the November 19 Online First issue of Annals of Surgery.
"Increasing evidence demonstrates that bariatric surgery can dramatically ameliorate type 2 diabetes," write Francesco Rubino, MD, from Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, and colleagues from the DSS Delegates. "Not surprisingly, gastrointestinal operations are now being used throughout the world to treat diabetes in association with obesity, and increasingly, for diabetes alone. However, the role for surgery in diabetes treatment is not clearly defined and there are neither clear guidelines for these practices nor sufficient plans for clinical trials to evaluate the risks and benefits of such 'diabetes surgery.'"
Development of Position Statement
The goal of this consensus conference was to issue guidelines for the use of gastrointestinal surgery for treatment of patients with T2DM and to develop a plan for further research. The DSS consensus document aimed to include the foundations underlying "diabetes surgery" and to present the opinions of leading scholars and evidence base supporting better access to surgical options, while preventing harm from unwarranted use of unproven procedures.
At the first International Conference on Gastrointestinal Surgery to Treat Type 2 Diabetes (the DSS), a multidisciplinary group of 50 voting delegates from around the world were convened in Rome, Italy, to review available scientific evidence. These data were evaluated and critiqued by the entire group to determine the strength of evidence and to draft consensus statements.
Draft statements from this meeting were reviewed, debated, edited, reevaluated, and presented for formal voting. Those statements that achieved consensus were summarized and distributed to all voting delegates for further input and final approval. At the 1st World Congress on Interventional Therapies for T2DM held in New York in September 2008, the final consensus statements were reviewed and discussed by representatives of several scientific societies to generate the current position statement.
The DSS acknowledged that in carefully selected patients, surgical approaches to treat T2DM are appropriate. In patients with poorly controlled diabetes and a body mass index (BMI) of 30 kg/m2 or more, for example, gastric bypass was recognized to be a reasonable treatment option.
Specific procedures may include Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding, or biliopancreatic diversion.
The DSS recommended further clinical trials to determine the precise role of surgery in patients who have less severe obesity and diabetes. Also strongly needed is further research on the mechanisms underlying surgical control of diabetes, which may further elucidate the pathophysiology of diabetes.
Recommendations
Specific recommendations in the DSS position statement, and their accompanying level of evidence rating, include the following:
In acceptable surgical candidates with a BMI of 35 kg/m2 or more whose disease is inadequately controlled by lifestyle and medical therapy, gastrointestinal surgery, such as RYGB, laparoscopic adjustable gastric banding, or biliopancreatic diversion, should be considered for the treatment of T2DM (level of evidence, A).
In suitable surgical candidates with mild to moderate obesity (BMI 30 - 35 kg/m2), a surgical approach may also be appropriate as a nonprimary option to treat inadequately controlled T2DM (level of evidence, B). RYGB may be an appropriate surgical option to treat diabetes in these patients (level of evidence, C).
In early clinical studies, novel gastrointestinal surgical techniques (eg, duodenal-jejunal bypass, ileal interposition, sleeve gastrectomy, and endoluminal sleeves) have shown promising results for the treatment of T2DM. At present, however, they should be used only in the context of institutional review board–approved and registered trials (level of evidence, A).
Establishing standards to measure clinical and physiologic outcomes of surgical treatment for T2DM is a high priority to obtain better-quality medical evidence (level of evidence, A).
To evaluate the usefulness of gastrointestinal surgery to treat T2DM, the DSS strongly encourages more randomized controlled trials (level of evidence, A).
Another important research priority is to identify the appropriate use of gastrointestinal surgery to treat T2DM in patients with a BMI of less than 35 kg/m2 (level of evidence, A). This should be accomplished with controlled clinical trials to assess the safety and efficacy of gastrointestinal metabolic surgery (level of evidence, A) and to identify parameters other than BMI to help guide selection of suitable patients (level of evidence, A).
Defining the optimal use of gastrointestinal surgery for treatment of T2DM in patients with a BMI of less than 35 kg/m2 would also be greatly facilitated by development of a standard registry/database (level of evidence, A).
Animal models can also offer helpful insights regarding the efficacy and mechanisms of gastrointestinal metabolic surgery used to treat T2DM (level of evidence, A).
Research on gastrointestinal metabolic surgery offers valuable, novel opportunities to investigate contributions of the gastrointestinal tract to glucose homeostasis and to clarify the pathophysiologic mechanisms of T2DM (level of evidence, A).
After laparoscopic adjustable gastric banding, weight loss alone accounts for diabetes control, based on available evidence from animal and clinical studies (level of evidence, A). However, mechanisms beyond those related to lowered food intake and body weight seem to be involved in intestinal bypass procedures such as RYGB, biliopancreatic diversion, and duodenal-jejunal bypass (level of evidence, A). In addition, distinct physiologic mechanisms that ameliorate T2DM are activated by anatomic changes in different regions of the gastrointestinal tract (level of evidence, B).
To improve understanding of gastrointestinal mechanisms of metabolic regulation and to use these insights to improve T2DM treatment, collaboration should be encouraged among endocrinologists, surgeons, and basic scientists (level of evidence, A).
To oversee the study and development of diabetes surgery, a multidisciplinary task force should be established, including endocrinologists, surgeons, clinical and basic investigators, bioethicists, and other appropriate experts (level of evidence, A).
"Delegates unanimously agreed that patients with inadequately controlled diabetes and BMI >35 kg/m2 should be considered for GI [gastrointestinal] surgery," the DSS authors conclude. "This concurs with existing NIH [National Institutes of Health] guidelines and with the 2009 American Diabetes Association standards of care position statement, and it further emphasizes the role of GI surgery in severely obese patients, where mounting evidence shows that surgery improves overall survival."
DSS was supported by Covidien, Ethicon, Allergan, Storz, GI Dynamics, Roche, Amylin, and Power Medical Interventions.
Ann Surg. Published online November 19, 2009.