PMID- 33452416 OWN - NLM STAT- MEDLINE DCOM- 20220124 LR - 20220907 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 45 IP - 3 DP - 2021 Mar TI - Altered bile acid kinetics contribute to postprandial hypoglycaemia after Roux-en-Y gastric bypass surgery. PG - 619-630 LID - 10.1038/s41366-020-00726-w [doi] AB - BACKGROUND/OBJECTIVES: Bile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown. METHODS: Plasma BA, fibroblast growth factor 19 (FGF19), 7alpha-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = 22). RESULTS: Fasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects. CONCLUSION: Altered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release. FAU - van den Broek, Merel AU - van den Broek M AD - Center for Obesity North Netherlands (CON), Department of Surgery, MCL, Leeuwarden, The Netherlands. AD - Faculty Campus Fryslan, University of Groningen, Leeuwarden, The Netherlands. FAU - de Heide, Loek J M AU - de Heide LJM AD - Center for Obesity North Netherlands (CON), Department of Surgery, MCL, Leeuwarden, The Netherlands. FAU - Sips, Fianne L P AU - Sips FLP AD - Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. FAU - Koehorst, Martijn AU - Koehorst M AD - Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - van Zutphen, Tim AU - van Zutphen T AD - Faculty Campus Fryslan, University of Groningen, Leeuwarden, The Netherlands. AD - Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Emous, Marloes AU - Emous M AD - Center for Obesity North Netherlands (CON), Department of Surgery, MCL, Leeuwarden, The Netherlands. FAU - van Faassen, Martijn AU - van Faassen M AD - Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Groen, Albert K AU - Groen AK AD - Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. AD - Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands. FAU - van Riel, Natal A W AU - van Riel NAW AUID- ORCID: 0000-0001-9375-4730 AD - Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. AD - Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands. FAU - de Boer, Jan F AU - de Boer JF AD - Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. AD - Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - van Beek, Andre P AU - van Beek AP AD - Center for Obesity North Netherlands (CON), Department of Surgery, MCL, Leeuwarden, The Netherlands. AD - Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Kuipers, Folkert AU - Kuipers F AUID- ORCID: 0000-0003-2518-737X AD - Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. f.kuipers@umcg.nl. AD - Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. f.kuipers@umcg.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210115 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Bile Acids and Salts) SB - IM MH - Adult MH - Bile Acids and Salts/*metabolism MH - Case-Control Studies MH - Female MH - *Gastric Bypass/adverse effects/statistics & numerical data MH - Humans MH - Hypoglycemia/*metabolism MH - Kinetics MH - Male MH - Middle Aged MH - Obesity/surgery MH - Postprandial Period/*physiology PMC - PMC7906904 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/01/17 06:00 MHDA- 2022/01/27 06:00 PMCR- 2021/01/15 CRDT- 2021/01/16 05:37 PHST- 2020/06/15 00:00 [received] PHST- 2020/12/03 00:00 [accepted] PHST- 2020/10/16 00:00 [revised] PHST- 2021/01/17 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/01/16 05:37 [entrez] PHST- 2021/01/15 00:00 [pmc-release] AID - 10.1038/s41366-020-00726-w [pii] AID - 726 [pii] AID - 10.1038/s41366-020-00726-w [doi] PST - ppublish SO - Int J Obes (Lond). 2021 Mar;45(3):619-630. doi: 10.1038/s41366-020-00726-w. Epub 2021 Jan 15.