肥胖者接受减肥手术 糖尿病风险降78%

瑞典歌德堡大学萨尔格学院的Lena M.S. Carlsson博士及其同事报告称，在一项纳入了3,000多例肥胖成年患者的前瞻性病例对照研究中，与常规方案相比，减肥手术后15年内2型糖尿病的发生率降低了78%。对于基线时空腹血糖受损的肥胖患者，减肥手术的作用更加显著，可使2型糖尿病风险降低87%(N. Engl. J. Med. 2012;367:695-704)。
 


瑞典肥胖者(SOS)试验共纳入了1,658例选择接受肥胖手术的患者以及1,771例与之匹配的对照患者。两组患者参加试验都是为了降低体重。所有患者基线时都没有糖尿病。

在减肥手术组中，311例接受的是胃束带手术，1,140例接受的是垂直束带胃成形术，另外207例接受的是胃旁路术。对照组患者则在其初级医疗保健中心接受传统的肥胖管理方案，可能涉及生活方式干预，包括给予饮食行为、食物选择、热量摄入、身体锻炼等方面的建议，也可能不予以任何治疗。大约一半的对照者(54%)表示接受了有关减肥的专业指导。

基线时两组患者的部分特征存在一些显著差异。减肥手术组患者的平均体重比对照组高6 kg，平均体重指数(BMI)也高于对照组(42.4 vs. 40.2 kg/m²)。此外，平均血压、总胆固醇水平、甘油三酯水平、吸烟者和不爱运动者所占的比例也都高于对照组。

在针对随访时间不足15年的病例以及死亡病例进行校正之后，15年参与率为54%。15年随访数据显示，减肥手术组1年后减重31 kg，但随后体重有所反弹，因此第10年和第15年时平均减重大约20 kg。对照组患者在整个试验期间体重增减都从未超过3 kg，无论其是否接受了专业人士的指导。

随访期间，减肥手术组和对照组分别有110例和392例患者出现了2型糖尿病，发病率分别为6.8和28.4例/1,000人年(P<0.001)。未经校正的危险比(HR)为0.22，经多因素校正后降至0.17。除治疗分组外，糖尿病结局的其他单因素预测因子包括基线血糖水平以及基线是否存在空腹血糖受损。

为了避免参与率偏低对试验结果造成的影响，Carlsson博士及其同事还开展了敏感性分析。结果显示，治疗分组对2型糖尿病发生率的影响在随访15年后至少与2年后和10年后一样显著。所有类型的减肥手术都与糖尿病发生率下降相关，各种手术类型之间的差异无统计学意义。此外，无论患者是否接受了专业的减肥指导，无论基线BMI高低，减肥手术都与2型糖尿病风险显著降低相关。

在减肥手术组中，共有3例患者(0.2%)在术后90天内死亡，245例(15%)至少出现了1种并发症。其中46例(2.8%)因病情严重需施行二次手术。

研究者指出，与其他以中等肥胖的糖尿病前期患者为对象的大规模长期试验中通过生活方式干预达到的风险下降程度相比(Lancet 2006;368:1673-9, Lancet 2009;374:1677-86和 Lancet 2008;371:1783-9)，该试验在空腹血糖受损患者中观察到的2型糖尿病风险下降程度至少高出了2倍。

研究者总结道，虽然减肥手术组的基线BMI高于对照组，其他危险因素也比对照组更严重，但减肥手术仍然使2型糖尿病的发病风险显著降低，并且与减肥手术的类型无关。“以上数据表明减肥手术对于偶发性2型糖尿病具有预防作用，尤其是对于空腹血糖受损的患者。而基线BMI并不会影响到减肥手术对于2型糖尿病的预防作用，这说明人体测量数据在选择减肥手术的适宜人群方面是无用的，而空腹血糖受损的相关数据可能有用。”

这项仍在进行中的SOS试验由瑞典研究理事会、瑞典萨尔格心血管与代谢研究中心战略研究基金会、瑞典联邦政府、VINNOVA-VINNMER项目和Wenner-Gren基金会联合资助。SOS试验曾有一部分经费来自罗氏、阿斯利康等企业提供给其中一名作者的研究经费。Carlsson博士声明接受了阿斯利康公司提供的咨询费，并且持有Sahltech公司的股份。其他研究者也声明存在一些经济利益冲突。

随刊述评：结果令人激动，但对许多患者而言不实际

SOS试验的长期数据的确令人激动和振奋，尤其是结果表明减肥手术可以防止糖代谢异常转化为真正意义上的糖尿病。既往研究结果提示减肥手术可以对血糖产生长期的控制作用，而这种作用是药物治疗所不能达到的，为此人们开始思考对于成年型糖尿病患者是否可以在病程早期即开始考虑行减肥手术(N. Engl. J. Med. 2012;367:764-5)。

然而，目前要对数百万符合条件的肥胖成年人施行减肥手术是不切实际的，也没有充分的理由这样做。这篇文章的作者也并不赞同这样的做法。这项研究的意义在于能激励我们去更加全面地了解各种减肥手术发挥其有益效应的潜在机制。明确机制之所以重要，是因为这将有助于我们识别出哪些患者最适合接受减肥手术。

导致2型糖尿病的病因是多方面的，这项长期试验显示手术并不能保证所有患者都不出现糖尿病。此外，其他侵袭性要小得多的干预措施也有可能达到降低2型糖尿病及其并发症发生率的理想效果。

述评作者DANNY O. JACOBS医生是美国杜克大学医学院的外科主任。Jacobs博士声明与爱惜康、Surgisphere和其他公司之间存在咨询、研究和/或教育服务等工作关系。

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By: MIRIAM E. TUCKER, Clinical Endocrinology News Digital Network

Bariatric surgery reduced the incidence of type 2 diabetes by 78% compared with usual care at 15 years in a prospective, case-matched study of more than 3,000 obese adults.

This significant risk reduction was seen with all types of bariatric surgery and regardless of baseline body mass index. And, it occurred despite the fact that the matching process unexpectedly resulted in the bariatric surgery group having a higher mean body weight and more severe risk factors at baseline than the controls.

The impact of bariatric surgery was even greater, with an 87% risk reduction, for those with impaired fasting glucose at baseline, said Dr. Lena M.S. Carlsson of the Sahlgrenska Academy at the University of Gothenburg, Sweden, and her associates (N. Engl. J. Med. 2012;367:695-704).

"Our data indicate that bariatric surgery has a preventive effect on incident type 2 diabetes, particularly in participants with impaired fasting glucose. In contrast, baseline BMI did not influence the preventive effect of bariatric surgery on type 2 diabetes, implying that anthropometric data are not useful in the selection of candidates for bariatric surgery, whereas data on impaired fasting glucose may be helpful," the authors wrote.

The finding comes from the Swedish Obese Subjects (SOS) trial, which included 1,658 patients who chose to undergo bariatric surgery and 1,771 matched controls. All patients in both groups entered the study with the intention of losing weight. None had diabetes at baseline.

In the bariatric surgery group, the types of procedures were banding in 311, vertical banded gastroplasty in 1,140, and gastric bypass in 207. Patients in the control group received the customary treatment for obesity at their primary health care centers, which in Sweden ranges from advanced lifestyle modification – including recommendations regarding eating behavior, food selection, energy intake, and physical activity – to no treatment. About half (54%) of the controls reported receiving professional guidance in attempts to lose weight.

There were several significant differences between groups at baseline. The bariatric surgery group weighed an average of 6 kg more than did the controls, and had a greater mean BMI (42.4 vs. 40.2 kg/m2). They also had higher mean blood pressures and total cholesterol and triglyceride levels, and were more likely to smoke and to be less active.

After adjustment for follow-up of less than 15 years and for death, the 15-year participation rate was 54%. At 15 years, the bariatric surgery group had lost 31 kg after 1 year, but then regained weight, so the average loss at 10 and 15 years was about 20 kg. The control group never lost or gained more than 3 kg over the entire study period, regardless of whether they had professional help.

During the follow-up, type 2 diabetes developed in 110 of the bariatric surgery patients and in 392 controls, corresponding to incidence rates of 6.8 and 28.4 cases per 1,000 person-years, respectively (P less than .001). The unadjusted hazard ratio was 0.22, which dropped to 0.17 following multivariate adjustments. Aside from treatment group, other strong univariate predictors of diabetes outcome were baseline blood glucose and the presence or absence of impaired fasting glucose, Dr. Carlsson and her associates reported.

In a sensitivity analysis performed to account for the low participation rate, the impact of treatment on the incidence of type 2 diabetes was at least as strong after 2 years and 10 years of follow-up as after 15 years. All types of bariatric surgery were associated with a reduced incidence of diabetes, with no significant differences among them. There were also no differences by receipt of professional weight-loss assistance, or by BMI at baseline, the investigators noted.

A total of 3 patients (0.2%) died within 90 days of surgery, and 245 patients in the surgery group (15%) reported at least one complication. Of those, 46 (2.8%) were serious enough to require a reoperation.

The risk reduction seen among those with impaired fasting glucose was at least twice as large as the risk reduction achieved with lifestyle interventions in large, long-term trials of moderately obese people with prediabetes (Lancet 2006;368:1673-9, Lancet 2009;374:1677-86, and Lancet 2008;371:1783-9), the investigators noted.

The ongoing SOS study is supported by grants from the Swedish Research Council, the Swedish Foundation for Strategic Research to the Sahlgrenska Center for Cardiovascular and Metabolic Research, the Swedish federal government, the VINNOVA-VINNMER program, and the Wenner-Gren Foundations. The SOS study has previously been supported by grants to one of the authors from Hoffmann-La Roche, AstraZeneca, and other companies. Dr. Carlsson reported receiving consulting fees from AstraZeneca and owning stock in Sahltech. Other coinvestigators also had financial disclosures.

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Provocative and Exciting, but Impractical for Many

The long-term findings of the SOS study are both provocative and exciting, especially the findings suggesting that bariatric surgery may prevent the conversion of abnormalities in glucose metabolism to frank diabetes.

The findings of previous studies, showing that bariatric surgery can have a prolonged, positive effect on blood sugar beyond that attainable with medication, have led to speculation about whether surgery might be considered earlier in the course of disease in patients with adult-onset diabetes.

However, it remains impractical and unjustified to contemplate the performance of bariatric surgery in the millions of eligible obese adults. And to be certain, the authors do not suggest such an approach. Rather, the current study should provide an impetus to develop a more complete understanding of the mechanisms by which the various bariatric procedures exert their beneficial effects. Such understanding will be important because it will enable the identification of individuals who are the most appropriate candidates for surgery.

The cause of type 2 diabetes is multifactorial, and this long-term study shows that surgery did not prevent the development of diabetes in all patients. Furthermore, it is possible that interventions that are even less invasive may accomplish the very desirable goal of decreasing the incidence of type 2 diabetes and its attendant complications.

DANNY O. JACOBS, M.D., is chair of surgery at the Duke University School of Medicine, Durham, N.C. These remarks were taken from his editorial accompanying Dr. Carlson’s report (N. Engl. J. Med. 2012;367:764-5). Dr. Jacobs has consulting, research, and/or educational services working relationships with Ethicon, Surgisphere, and other companies.