Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery
Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery
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DOI：
10.2337/dc16-0145
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发表时间：
2016-06-01
期刊：
影响因子：
16.2
通讯作者：
Cummings, David E.
中科院分区：
文献类型：
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作者：
Batterham, Rachel L.;Cummings, David E.
20多年前，Pories等人发表了一篇开创性的文章《谁会想到？》手术被证明是治疗成人糖尿病最有效的方法。这是基于他们的观察，减肥手术使肥胖的2型糖尿病（T2DM）患者的血糖水平迅速正常化，10年后，几乎90%的人没有糖尿病。Pories等人认为热量限制发挥了关键作用，近端肠道营养物质排除、远端肠道营养物质快速输送以及肠道激素的作用等因素的相对作用需要进一步研究。这些减肥手术后T2DM改善/缓解的发现已被广泛复制，同时减肥手术可预防或延迟T2DM的发生。在随后的二十年中，胃肠道（GI）的重要血糖调节作用已经得到了牢固的确立。然而，减肥手术有益降血糖作用的生理和分子机制仍不完全清楚。除了Pories等人提出的机制外，胆汁酸代谢、胃肠道营养感知和葡萄糖利用、肠促胰岛素、可能的抗肠促胰岛素和肠道微生物组的变化也涉及其中。这些变化通过外周和/或中枢途径起作用，导致肝脏葡萄糖生成减少，组织葡萄糖摄取增加，胰岛素敏感性改善，细胞功能增强。多种因素，而不是单一的总体机制，可能介导术后血糖改善，影响因素因手术方式而异。因此，不同的减肥/代谢程序为我们提供了探索胃肠道生理学的实验工具。通过应用详细的表型、基因组学、代谢组学和肠道微生物组研究，采用这种方法将增强我们对代谢调节的理解，并有助于确定新的治疗靶点。
More than 20 years ago, Pories et al. published a seminal article, Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus. This was based on their observation that bariatric surgery rapidly normalized blood glucose levels in obese people with type 2 diabetes mellitus (T2DM), and 10 years later, almost 90% remained diabetes free. Pories et al. suggested that caloric restriction played a key role and that the relative contributions of proximal intestinal nutrient exclusion, rapid distal gut nutrient delivery, and the role of gut hormones required further investigation. These findings of T2DM improvement/remission after bariatric surgery have been widely replicated, together with the observation that bariatric surgery prevents or delays incident T2DM. Over the ensuing two decades, important glucoregulatory roles of the gastrointestinal (GI) tract have been firmly established. However, the physiological and molecular mechanisms underlying the beneficial glycemic effects of bariatric surgery remain incompletely understood. In addition to the mechanisms proposed by Pories et al., changes in bile acid metabolism, GI tract nutrient sensing and glucose utilization, incretins, possible anti-incretin(s), and the intestinal microbiome are implicated. These changes, acting through peripheral and/or central pathways, lead to reduced hepatic glucose production, increased tissue glucose uptake, improved insulin sensitivity, and enhanced -cell function. A constellation of factors, rather than a single overarching mechanism, likely mediate postoperative glycemic improvement, with the contributing factors varying according to the surgical procedure. Thus, different bariatric/metabolic procedures provide us with experimental tools to probe GI tract physiology. Embracing this approach through the application of detailed phenotyping, genomics, metabolomics, and gut microbiome studies will enhance our understanding of metabolic regulation and help identify novel therapeutic targets.