Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance

Jørgensen, Nils B.; Jacobsen, Stine; Dirksen, Carsten; Bojsen‐Møller, Kirstine N.; Navér, Lars; Hvolris, Lisbeth E.; Clausen, T.; Wulff, Birgitte S.; Worm, Dorte; Hansen, Dorte L.; Madsbad, Sten; Holst, Jens J.

doi:10.1152/ajpendo.00073.2012

Cited by 281 publications

(297 citation statements)

References 49 publications

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“…Most short-term studies (< 2 months after surgery) report unchanged or decreased levels of total BAs [26][27][28], while most studies reporting data from several months and years after surgery report increased concentrations [18,20,[29][30][31][32]. Our findings are in accordance with the existent literature, and extend the current knowledge by showing that the BA levels apparently continue to increase up to 5 years after RYGB.…”

Section: Discussionsupporting

confidence: 91%

“…These observations must be considered as explorative and no conclusions about a causal relationship between these variables and bile acid concentrations can be done. As in several other studies, we were not able to demonstrate any correlation between BAs and markers of glucose metabolism and insulin resistance [18,20,27,28]. We found large variations in fasting BA concentrations both within and between individuals, as depicted in Figure 1.…”

Section: Discussionsupporting

confidence: 48%

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Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Risstad

Kristinsson

Fagerland

et al. 2017

Surgery for Obesity and Related Diseases

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(2017). Bile acid profiles over 5 years following gastric bypass and duodenal switch -Results from a randomized clinical trial. Surgery for obesity and related diseases. https://doi.org/10.1016/j.soard.2017.05.024Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 48%

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Risstad

Kristinsson

Fagerland

et al. 2017

Surgery for Obesity and Related Diseases

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“…Second, we previously demonstrated, using a pancreatic clamp, that the effects of the GLP-1 receptor agonist on the CNS responses to food stimuli were independent of changes in insulin levels (5). Third, although others have shown that insulin levels may increase at 3 months after RYGB, this was not observed 1 week after RYGB (38). It also could be suggested that changes in glucose levels after RYGB may affect our observed findings.…”

Section: Discussionmentioning

confidence: 57%

Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues

et al. 2017

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OBJECTIVEIt has been suggested that weight reduction and improvements in satiety after Rouxen-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS. RESEARCH DESIGN AND METHODSEffects of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus placebo before and after RYGB. RESULTSAfter RYGB, CNS activation was reduced in the rolandic operculum and caudate nucleus in response to viewing food pictures (P = 0.03) and in the insula in response to consumption of palatable food (P = 0.003). GLP-1 levels were significantly elevated postoperatively (P < 0.001). After RYGB, GLP-1 receptor blockade resulted in a larger increase in activation in the caudate nucleus in response to food pictures (P = 0.02) and in the insula in response to palatable food consumption (P = 0.002). CONCLUSIONSWe conclude that the effects of RYGB on CNS activation in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB.Bariatric surgery is currently the most effective therapeutic modality for severe obesity in terms of substantial weight loss and long-term efficacy (1). The most commonly performed procedure is Roux-en-Y gastric bypass surgery (RYGB), which comprises the formation of a small gastric pouch, which is connected to the midjejunum, bypassing the duodenum and proximal jejunum. This may lead to reduced ingestive capacity and

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“…Human studies report improved b-cell function after RYGB in T2D patients and nondiabetic controls (15,16). Studies aiming to uncover the mechanism have been performed in rodents (17).…”

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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Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance

Cited by 281 publications

References 49 publications

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues

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

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