2型糖尿病的一种新范式：它会是一种前肠疾病吗？
A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?
作者信息
Hickey M S, Pories W J, MacDonald K G, Cory K A, Dohm G L, Swanson M S, Israel R G, Barakat H A, Considine R V, Caro J F, Houmard J A
机构信息
Department of Exercise and Sport Science, Colorado State University, Ft. Collins, USA.
出版信息
Ann Surg. 1998 May;227(5):637-43; discussion 643-4. doi: 10.1097/00000658-199805000-00004.
SUMMARY BACKGROUND DATA
We previously reported, in a study of 608 patients, that the gastric bypass operation (GB) controls type 2 diabetes mellitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible to reduce the mortality from diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This control of diabetes has been ascribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss was really the important factor.
METHODS
Fasting plasma insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 months after surgery versus a control group of six women who did not undergo surgery and were similarly weight-stable. The two groups were matched in age, percentage of fat, body mass index, waist circumference, and aerobic capacity.
RESULTS
Even though the two groups of patients were closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgical group demonstrated significantly lower levels of serum leptin, fasting plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was significantly higher in the surgical group. Finally, self-reported food intake was significantly lower in the surgical group.
CONCLUSIONS
Weight loss is not the reason why GB controls diabetes mellitus. Instead, bypassing the foregut and reducing food intake produce the profound long-term alterations in glucose metabolism and insulin action. These findings suggest that our current paradigms of type 2 diabetes mellitus deserve review. The critical lesion may lie in abnormal signals from the gut.
摘要 背景数据：我们之前在一项对608例患者的研究中报告，胃旁路手术（GB）在控制病态肥胖患者的2型糖尿病方面比任何药物治疗都更有效。此外，我们首次表明降低糖尿病死亡率是可能的；胃旁路手术将每年的死亡几率从4.5%降至1%。糖尿病的这种控制归因于手术引起的体重减轻。这些针对体重稳定女性的研究旨在确定体重减轻是否真的是重要因素。
方法
在精心匹配的队列中测量空腹血浆胰岛素、空腹血糖、最小模型衍生的胰岛素敏感性和瘦素水平：6例接受胃旁路手术且术后24至30个月体重稳定在较低水平的女性，与6例未接受手术且体重同样稳定的女性对照组。两组在年龄、脂肪百分比、体重指数、腰围和有氧能力方面相匹配。
结果
尽管两组患者在体重、年龄、脂肪百分比甚至有氧能力方面紧密匹配且两组体重均保持稳定，但与对照组相比，手术组的血清瘦素、空腹血浆胰岛素和空腹血糖水平显著更低。同样，手术组最小模型衍生的胰岛素敏感性显著更高。最后，手术组自我报告的食物摄入量显著更低。
结论
体重减轻不是胃旁路手术控制糖尿病的原因。相反，绕过前肠和减少食物摄入量会导致葡萄糖代谢和胰岛素作用发生深刻的长期改变。这些发现表明我们目前关于2型糖尿病的范式值得审视。关键病变可能在于来自肠道的异常信号。
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