Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake

Kirstine Nyvold Bojsen-Møller*, Maria Saur Svane, Christoffer Martinussen, Carsten Dirksen, Nils Bruun Jørgensen, Jens Erik Beck Jensen, Christian Zinck Jensen, Signe Sørensen Torekov, Viggo Bjerregaard Kristiansen, Jens Frederik Rehfeld, Jette Bork-Jensen, Niels Grarup, Torben Hansen, Bolette Hartmann, Jens Juul Holst, Sten Madsbad

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Background/Objectives: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure. Subjects/Methods: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting. Results: On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (−1% [−13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]). Conclusions: Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.

OriginalsprogEngelsk
TidsskriftInternational Journal of Obesity
Vol/bind47
Udgave nummer11
Sider (fra-til)1143-1151
Antal sider9
ISSN0307-0565
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors are indebted to the patients for their willingness to participate in the study and are grateful for technical assistance from Alis Andersen and Sussi Polmann (Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Denmark) and Lene Albak (Dept. of Biomedical Sciences, University of Copenhagen, Denmark). This study was supported by a grant from the Danish Council for Independent Research, Denmark (DFF – 4092 – 00218). Further, this project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 695069-BYPASSWITHOUTSURGERY). KNBM is supported by a grant from the Novo Nordisk Foundation (NNF 18OC0032330).

Publisher Copyright:
© 2023, The Author(s).

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