Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass

Dirksen, Carsten; Jørgensen, Nils B.; Bojsen‐Møller, Kirstine N.; Jacobsen, Siv H.; Hansen, Dorte L.; Worm, Dorte; Holst, Jens J.; Madsbad, Sten

doi:10.1007/s00125-012-2556-7

Cited by 211 publications

(173 citation statements)

References 105 publications

(56 reference statements)

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“…The mechanism underlying this rapid remission remains unknown. A body of evidence shows increased insulin secretion and levels of GLP-1 after RYGB (15). However, it is not known how b-cell mass is affected by RYGB.…”

Section: Discussionmentioning

confidence: 99%

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

et al. 2014

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The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on b-cell function and b-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in b-cell mass, islet number, and number of extraislet b-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved b-cell function and b-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical.Roux-en-Y gastric bypass surgery (RYGB) leads to remission of type 2 diabetes (T2D) in most patients within days after surgery (1). Importantly, this occurs long before any substantial weight loss has occurred (2). The reason for this remains a controversy, as studies have shown that the beneficial effects of RYGB on T2D are weight loss independent (e.g., [3]), while others suggest that they result from reduced food intake (4). Clinical studies have shown that RYGB has greater effect on remission of T2D than, for example, vertical sleeve gastrectomy, despite similar weight loss (5). This is in support of weight-independent factors underlying the resolution of T2D upon RYGB. One factor, accounting for the beneficial metabolic effects of RYGB, may be changes in circulating levels of gut hormones and their effects on the islets. In particular, increased levels of the incretin hormone glucagon-like peptide 1 (GLP-1) have been implicated as a factor contributing to remission of T2D (2,6). The effect of RYGB on glucose-dependent insulinotropic peptide (GIP) is less clear (6,7). Other factors, including gut microbiota (8), intestinal glucose sensing (9), and bile acids (10), may also contribute. Nevertheless, it is of great clinical importance to resolve this issue, as it will have a strong impact on how treatment for a large group of patients is devised. In fact, if a specific mechanism were to be identified, it could be used as the basis for a new treatment modality.One problem in the dissection of effects of RYGB on glucose metabolism is that studies on b-cell mass in humans are lacking, and it is extremely difficult to generalize from data in rodents (11) because of huge differences in pancreatic anatomy and physiology between the species. To circumvent these problems, we devel...

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Section: Discussionmentioning

confidence: 99%

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

et al. 2014

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“…Indeed, glucagon-like peptide-1 (GLP-1) analogs and inhibitors of GLP-1 degradation are now widely prescribed for the treatment of type 2 diabetes, offering additional beneficial effects on body weight compared with conventional insulin secretagogues (5,6). As increasing evidence implicates enteroendocrine L-cells, which secrete GLP-1 together with the anorectic peptides oxyntomodulin and peptideYY (PYY), as substantial players in postbariatric physiology (7), a question that has raised considerable interest is whether L-cells or their close relatives (8,9) produce additional peptides of therapeutic significance.…”

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confidence: 99%

Insulin-like peptide 5 is an orexigenic gastrointestinal hormone

Grosse

Heffron

Burling

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

126

205

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The gut endocrine system is emerging as a central player in the control of appetite and glucose homeostasis, and as a rich source of peptides with therapeutic potential in the field of diabetes and obesity. In this study we have explored the physiology of insulin-like peptide 5 (Insl5), which we identified as a product of colonic enteroendocrine L-cells, better known for their secretion of glucagon-like peptide-1 and peptideYY. i.p. Insl5 increased food intake in wild-type mice but not mice lacking the cognate receptor Rxfp4. Plasma Insl5 levels were elevated by fasting or prolonged calorie restriction, and declined with feeding. We conclude that Insl5 is an orexigenic hormone released from colonic L-cells, which promotes appetite during conditions of energy deprivation.

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“…Changes in the postprandial secretory pattern of incretins, such as glucagon-like peptide 1, are generally suggested as the major component of this effect, although alterations in dietary habits, gastric emptying, bile acids, and/or microbiota have also been put forward as possible mechanisms that could explain this phenomenon (19). Indeed, remission of type 2 diabetes has been reported within days to weeks after GBP surgery, before substantial weight reduction has occurred (20,21).…”

mentioning

confidence: 99%

Weight Change–Adjusted Effects of Gastric Bypass Surgery on Glucose Metabolism: 2- and 10-Year Results From the Swedish Obese Subjects (SOS) Study

et al. 2015

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OBJECTIVEIt has been suggested that weight change-independent effects on fasting insulin and glucose levels are present after gastric bypass (GBP) but not after banding and vertical banded gastroplasty (VBG). We therefore evaluated weight change-adjusted effects of GBP, compared with restrictive surgical procedures, on long-term changes in fasting levels of glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in the Swedish Obese Subjects (SOS) study. RESEARCH DESIGN AND METHODSParticipants who completed the 2-year (n = 1,762) and/or the 10-year (n = 1,216) follow-up were divided into three weight change classes (weight loss >30%, 20-30%, or £20%), and by surgical method (banding, VBG, or GBP). Glucose, insulin, and HOMA-IR changes were analyzed in relation to weight change over 2 and 10 years. Analyses were performed in the full cohort and also in subgroups based on baseline glucose status. RESULTSWithin weight change classes, reductions in glucose, insulin, and HOMA-IR were similar in the three surgery groups both at 2 and at 10 years. Reductions in glucose, insulin, and HOMA-IR increased with increasing weight loss, and changes were typically related to weight change within each surgery group. Moreover, the association between weight change and change in glucose, insulin, or HOMA-IR did not differ between the surgery groups at 2 and 10 years. When patients were subdivided also by baseline glucose status, similar relationships between weight changes and changes in glucose, insulin, and HOMA-IR were observed. CONCLUSIONSEven though weight loss-independent effects are important for short-term diabetes remission, our results suggest that degree of weight loss is more important for long-term reductions in fasting insulin and glucose than choice of bariatric surgery procedure.

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Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass

Cited by 211 publications

References 105 publications

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

Insulin-like peptide 5 is an orexigenic gastrointestinal hormone

Weight Change–Adjusted Effects of Gastric Bypass Surgery on Glucose Metabolism: 2- and 10-Year Results From the Swedish Obese Subjects (SOS) Study

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