Role of the Gut on Glucose Homeostasis: Lesson Learned from Metabolic Surgery

Current Atherosclerosis Reports, Feb 2017

Purpose of Review Bariatric surgery was initially intended to reduce weight, and only subsequently was the remission of type two diabetes (T2D) observed as a collateral event. At the moment, the term “metabolic surgery” is used to underline the fact that this type of surgery is performed specifically to treat diabetes and its metabolic complications, such as hyperlipidemia. Recent Findings Randomized, controlled studies have recently supported the use of bariatric surgery, and in particular of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) as an effective treatment for decompensated T2D. The lesson learned from these randomized and many other non-randomized clinical studies is that the stomach and the small intestine play a central role in glucose homeostasis. Bypassing the duodenum and parts of the jejunum exerts a substantial effect on insulin sensitivity and secretion. In fact, with BPD, nutrient transit bypasses duodenum, the entire jejunum and a small portion of the ileum, resulting in reversal of insulin sensitivity back to normal and reduction of insulin secretion, whereas RYGB has little effect on insulin resistance but increases insulin secretion. Hypotheses concerning the mechanism of action of metabolic surgery for diabetes remission vary from theories focusing on jejunal nutrient sensing, to incretin action, to the blunted secretion of putative insulin resistance hormone(s), to changes in the microbiota. Summary Whatever the mechanism, metabolic surgery has the undoubted merit of exposing the central role of the small intestine in insulin sensitivity and glucose homeostasis.

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Role of the Gut on Glucose Homeostasis: Lesson Learned from Metabolic Surgery

Curr Atheroscler Rep Role of the Gut on Glucose Homeostasis: Lesson Learned from Metabolic Surgery V. Kamvissi-Lorenz 0 1 2 3 M. Raffaelli 0 1 2 3 S. Bornstein 0 1 2 3 G. Mingrone 0 1 2 3 0 Department of Surgery, Catholic University , Rome , Italy 1 Diabetes and Nutritional Sciences, King's College London , Henr. Rahp. R. 3.6, Guy's Campus, 19 Newcomen Street, London SE1 1UL , UK 2 Department of Medicine 3, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden , Dresden , Germany 3 Department of Internal Medicine, Catholic University , Rome , Italy Purpose of Review Bariatric surgery was initially intended to reduce weight, and only subsequently was the remission of type two diabetes (T2D) observed as a collateral event. At the moment, the term “metabolic surgery” is used to underline the fact that this type of surgery is performed specifically to treat d i a b e t e s a n d i t s m e t a b o l i c c o m p l i c a t i o n s , s u c h as hyperlipidemia. Recent Findings Randomized, controlled studies have recently supported the use of bariatric surgery, and in particular of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) as an effective treatment for decompensated T2D. The lesson learned from these randomized and many other non-randomized clinical studies is that the stomach and the small intestine play a central role in glucose homeostasis. Bypassing the duodenum and parts of the jejunum exerts a substantial effect on insulin sensitivity and secretion. In fact, with BPD, nutrient transit bypasses duodenum, the entire jejunum and a small portion of the ileum, resulting in reversal of insulin sensitivity back to normal and reduction of insulin secretion, whereas RYGB has little effect on insulin resistance but increases insulin secretion. Hypotheses concerning the mechanism of action of metabolic surgery for diabetes remission vary from theories focusing on jejunal nutrient sensing, to incretin action, to the blunted secretion of putative insulin resistance hormone(s), to changes in the microbiota. Summary Whatever the mechanism, metabolic surgery has the undoubted merit of exposing the central role of the small intestine in insulin sensitivity and glucose homeostasis. Bariatric surgery; Gastric bypass; Biliopancreatic bypass; Sleeve gastrectomy; Diabetes mellitus; Obesity - In the last few years, a great deal of attention has been focused on the effects of bariatric surgery on diabetes remission and changes in glucose homeostasis. In fact, a foremost achievement of bariatric surgery has been to uncover the role of the small intestine in glucose metabolism. The term “bariatric” derives from the Greek word “baros”, meaning weight. Bariatric surgery was in fact developed to cure morbidly obese subjects. The idea of a surgical treatment of obesity developed in the early 1950s fortuitously from the observation that patients that underwent gastrointestinal resections for various reasons were likely to lose weight. An international consensus conference held in Rome in 2007 - the “Diabetes Surgery Summit”—underlined the need to use the adjective “metabolic” instead of “bariatric” in order to highlight the efficacy of bariatric surgery from the metabolic point of view even in the absence of weight reduction [1]. Indeed, the designation of “metabolic surgery” was previously used by Buchwald and Varco [2] for some operations like the portal diversion to improve glycogen storage diseases or the partial ileal bypass for hyperlipidemia. In view of the weight independent effects of some types of gastrointestinal surgery for obesity, Rubino [3] proposed to use metabolic surgery not only for uncontrolled T2D, but also for patients with the metabolic syndrome, non-alcoholic steatohepatitis (NASH), and increased cardiovascular risk, presuming a neuroendocrine mechanism of action for this surgery. Here, we seek to briefly summarize recent findings from randomized trials on the impact of bariatric surgery on metabolic outcomes, and devote the remainder this article to presenting a new perspective on the role played by the small intestine in driving the changes in insulin sensitivity and secretion and glycemic control that occur after some types of bariatric surgery. A better understanding of gut function in glucose disposal might help to develop, in the near future, a medical treatment for T2D that mimics the effects of gastrointestinal surgery. Review of Recent Randomized Trials Randomized controlled trials (RCT) have shown that bariatric/metabolic surgery is effective in treating type 2 diabetes mellitus. An extensive review of the literature at this regard is behind our scope; therefore, we have summarized only the results of some relevant RCTs. The first evidence of the efficacy of bariatric surgery on T2DM is that from Dixon et al.’s [4] RCT showing that T2DM remission was present in 73% of the patients who underwent LAGB and in 13% of those in the conventional therapy (...truncated)


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V. Kamvissi-Lorenz, M. Raffaelli, S. Bornstein, G. Mingrone. Role of the Gut on Glucose Homeostasis: Lesson Learned from Metabolic Surgery, Current Atherosclerosis Reports, 2017, pp. 9, Volume 19, Issue 2, DOI: 10.1007/s11883-017-0642-5