胃旁路术可使轻度肥胖患者的糖尿病缓解

作者：JENNIE SMITH首都医科大学附属北京世纪坛医院普外一区（胃肠肝胆肿瘤外科）闫巍

    《糖尿病护理》(Diabetes Care) 2012年7月刊发的一项长期研究显示，轻度肥胖的重度糖尿病患者在胃旁路术后获得明显缓解，88%的患者在术后6个月内获得持续的疾病缓解，并且10年心血管风险明显降低。此外，无1例患者出现死亡、主要手术并发症、体重过度降低和营养不良。

    目前，美国国立卫生研究院仅建议将减肥手术用于体重指数(BMI)≥40 kg/m2的患者或＞35 kg/m2合并重度糖尿病等疾病的患者。既往研究显示，极度肥胖的糖尿病患者的疾病活动性在Roux-en-Y胃旁路(RYGB)手术后明显降低，约80%~85%的患者获得持续缓解。越来越多的证据表明，该手术可诱导独立于体重减轻之外的激素性和代谢性抗糖尿病应答。

    这项研究由巴西圣保罗Oswaldo Cruz医院和Marcia Maria Braido医院的Ricardo V. Cohen博士及其同事进行，旨在探讨BMI较低且糖尿病控制不佳的患者在接受RYGB手术后是否同样能获得明显益处。

    该研究纳入接受腹腔镜下RYGB手术的40例男性和26例女性患者，手术时的年龄为31~63岁，BMI为30.0~34.9 kg/m2，糖尿病病程≥7年。尽管使用胰岛素和(或)口服糖尿病药物(7例使用胰岛素)，这些患者手术时的平均HbA1c水平为9.7%。所有患者均接受了为期5年的随访。

    结果显示，术后26周内，88%的患者能够停用糖尿病药物且在随访期间不需重新使用糖尿病药物即可将HbA1c水平维持在6.5%以下。在术后3~14周能够停用胰岛素和(或)降低口服药物剂量的11%患者中观察到改善但未达到缓解。术后7个月，1例患者的血糖控制无改善，但能够停用胰岛素及通过口服药物控制糖尿病。整个队列的平均HbA1c水平在研究期间从9.7%逐渐降至5.9%。空腹血糖(FPG)从156 mg/dl 降至97 mg/dL。这些改变多数在术后6个月内发生。

    所有患者的腰围均进行性缩小，总体重也进行性降低，但体重降幅直至术后5年后才与FPG和HbA1c降幅相符，术后5年后研究者观察到体重降幅与FPG降幅之间显著相关，但与HbA1c降幅无关联。此外，尽管C肽改变/血糖改变之比在术后显著增加，但增幅与体重降幅无关。所有这些结果表明，手术可诱导独立于体重减轻之外的抗糖尿病作用。

    该队列的预测10年心血管病风险在术后出现降低，其中冠心病(CHD)风险降低71%，致死性CHD风险降低84%，卒中风险降低50%，致死性卒中风险降低57%。术后随访期间观察到高血压和血脂异常情况也获得缓解：在26例基线时有高血压的患者中，15例(58%)的高血压在术后获得缓解，在33例高胆固醇血症患者中，21例(64%)获得缓解，在31例高甘油三酯血症患者中，18例(58%)获得缓解。重要的是，无1例患者的体重过度降低或出现营养不良。随访期间观察到的最低BMI为23.6。

    研究者表示，上述结果表明RYGB手术能够安全有效地缓解BMI 30~35 kg/m2患者的2型糖尿病和相关合并症，进而降低预测的心血管病风险。该研究结果尚有待随机对照研究加以证实。

Gastric Bypass Induces Diabetes Remission in Mildly Obese

BY. JENNIE SMITH

    Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

    No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8).

    Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m2 or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

    People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

    Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

    For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

    Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

    Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

    Mean HbA1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

    All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

    The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

    Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

    The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they “indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m2.”

    While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, “our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery.”

    Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.