Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.

The decreased postprandial bile acid response in obese subjects compared with normal weight subjects may partly explain the suboptimal GLP-1 and PYY responses and could affect appetite, glycaemic control and energy expenditure.

Summary Background  Gut hormones peptide YY (PYY) and glucagon‐like peptide‐1 (GLP‐1) play an integral role in appetite control and energy homeostasis. Entero‐endocrine L‐cells can be stimulated by nutrients and or bile acids to co‐secrete PYY and GLP‐1. The aim of this study was to determine the response of bile acids, PYY, GLP‐1 and ghrelin after a test meal. Design  Twelve subjects with a BMI of 22·8 (0·52) kg/m2 [mean (SEM)] received a 400 kcal test meal after which blood samples were taken every 30 min from 0 to 180 min. PYY, GLP‐1 and ghrelin were measured by radioimmunoassays. Fractionated bile acids were measured by HPLC‐MSMS. Results  PYY positively correlated with glycochenodeoxycholic acid (GCDCA) (rs = 0·23, P = 0·03) and taurochenodeoxycholic acid (TCDCA) (rs = 0·26, P = 0·02). GLP‐1 positively correlated with GCDCA (rs = 0·22, P = 0·047) and glycodeoxycholic acid (GDCA) (rs = 0·3, P = 0·005). Ghrelin negatively correlated with GDCA (rs = −0·45, P≤ 0·0001), TCDCA (rs = −0·23, P = 0·034) and taurodeoxycholic acid (TDCA) (rs = −0·44, P≤ 0·0001). Conclusion  PYY and GLP‐1 responses correlated with chenodeoxycholic acid (CDCA) counterparts, whereas ghrelin negatively correlated with deoxycholic acid (DCA) counterparts. Specific bile acids may thus differentially affect entero‐endocrine cells.

Association of serial measurements of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults deFilippi CR, de Lemos JA, Christenson RH, et al.