Review Article: The Emerging Interplay Among the Gastrointestinal Tract, Bile Acids and Incretins in the Pathogenesis of Diabetes and Non-alcoholic Fatty Liver Disease

A. Zarrinpar; R. Loomba


Aliment Pharmacol Ther. 2012;36(10):909-921. 

In This Article

The Effects of Gastric Bypass Surgery on Glucose Homoeostasis

A majority of patients who undergo Roux-en-Y gastric bypass (RYGB) surgery are either completely cured of T2DM or have a large improvement despite initial negligible weight loss. A meta-analysis of 136 bariatric surgery studies reported that, of individuals who underwent gastric bypass, T2DM was resolved in 83.7%, and resolved or improved in 93.2%.[157] These patients achieve normal fasting plasma glucose and haemoglobin A1C levels.[158–161] These changes occur before the patient has lost significant amounts of weight,[160,161] suggesting that the improvements in glycaemic control following RYGB may be caused by effects other than weight loss. As the primary objective of these procedures is to manipulate and reorient the gut, it is presumed that this improvement is mediated or potentiated by the gut.

A potential explanation for the improvements in glycaemic control seen following RYGB is altered secretion of GLP-1 secondary to gastrointestinal manipulation and reorientation. Patients who have undergone RYGB have significantly increased postprandial GLP-1 and insulin secretion, compared with obese and lean controls, and patients who had lost an equivalent amount of weight by gastric banding.[162] This could be because more ingested material, especially fats and carbohydrates, are reaching the ileum and causing an increase in GLP-1 release from L cells.

Interestingly, altered gastrointestinal anatomy after RYGB may also affect enterohepatic recirculation of bile acids and contribute to improved glycaemic control. A study of patients who had undergone RYGB revealed that total fasting serum bile acids increased two-fold when compared with overweight or morbidly obese control participants.[163] A closer analysis showed that multiple bile acid subfractions, including both primary and secondary bile acids, reached statistical significance. Total serum bile acids were inversely correlated with 2-h postprandial glucose levels and positively correlated with GLP-1 levels. Similarly, in another study in Japanese adults who had undergone laparoscopic bariatric surgery, a positive correlation was observed between the changes in serum concentration of primary bile acids and plasma levels of GIP 1 month after surgery.[164] The mechanism by which bile acids in the enterohepatic circulation increase is not fully understood; Patti et al. proposed that their observation that both primary and secondary bile acid levels are increased in the systemic circulation suggests that this occurs via increased uptake of bile acids in the intestines.[163] This increase could mediate its effects on GLP-1 increases through TGR5 receptors.