Altered bile acid kinetics contribute to postprandial hypoglycaemia after Roux-en-Y gastric bypass surgery

• Published in: International Journal of Obesity Vol. 45; no. 3; pp. 619 - 630
• Main Authors: van den Broek, Merel, de Heide, Loek J. M., Sips, Fianne L. P., Koehorst, Martijn, van Zutphen, Tim, Emous, Marloes, van Faassen, Martijn, Groen, Albert K., van Riel, Natal A. W., de Boer, Jan F., van Beek, André P., Kuipers, Folkert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2021; Nature Publishing Group
• Subjects: 631/443/319/1642; 631/45/72/1201; Adult; Bile; Bile acids; Bile Acids and Salts - metabolism; Case-Control Studies; Cholecystectomy; Complications and side effects; Detergents; Development and progression; Eating (Physiology); Epidemiology; Female; Fibroblast growth factors; Gallbladder; Gastric bypass; Gastric Bypass - adverse effects; Gastric Bypass - statistics & numerical data; Gastrointestinal surgery; Glucose; Growth factors; Health aspects; Health Promotion and Disease Prevention; Heart surgery; Humans; Hypoglycemia; Hypoglycemia - metabolism; Ingestion; Insulin; Internal Medicine; Intestinal bypass; Intestine; Kinetics; Male; Mathematical models; Meals; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic rate; Middle Aged; Modulators; Obesity - surgery; Plasma; Postprandial Period - physiology; Public Health; Risk factors; Surgery; Netherlands
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-020-00726-w

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), 7α-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.