Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes

Abstract

INTRODUCTION Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM. METHODS Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM. RESULTS A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found. CONCLUSIONS This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

“…Most short-term studies (< 2 months after surgery) report unchanged or decreased levels of total BAs [26][27][28], while most studies reporting data from several months and years after surgery report increased concentrations [18,20,[29][30][31][32]. Our findings are in accordance with the existent literature, and extend the current knowledge by showing that the BA levels apparently continue to increase up to 5 years after RYGB.…”

“…A study of patients with type 2 diabetes observed, contrary to their hypothesis, an increase in this ratio after RYGB [28]. Our study, which mostly included nondiabetic subjects, also demonstrated an increased ratio after both procedures at 5 years.…”

“…These observations must be considered as explorative and no conclusions about a causal relationship between these variables and bile acid concentrations can be done. As in several other studies, we were not able to demonstrate any correlation between BAs and markers of glucose metabolism and insulin resistance [18,20,27,28]. We found large variations in fasting BA concentrations both within and between individuals, as depicted in Figure 1.…”

“…Most studies report increased BA concentrations after RYGB [16,17], but studies exploring changes in BA fractions are inconsistent [18][19][20]. There are, to our knowledge, no reports of changes in BA profiles after BPD/DS, and there are no reports on BA profiles long term after bariatric surgery.…”

Obesity diabetes and the role of bile acids in metabolism

“…The authors concluded that the bile acids did not explain the rapid improvement in glucose and lipid metabolism or the stimulation of GLP-1. Temporal changes in bile acids and 12a-hydroxylation after Roux en Y operations have been recently reported by Dutia et al [43] They found that fasting bile acids were generally reduced at 1 month, but increased after 2 years, whereas postprandial bile acids were unchanged at 1 month, but there was an exaggerated peak at 2 years. The ratio of 12a-hydroxylated bile acids to non 12a bile acids was increased at 2 years, but not at 1 month, again suggesting that an early improvement in glucose metabolism is unrelated to the changes in bile acids.…”