Endocrine Abstracts

Background: Bariatric surgery, dietary restriction and gut hormones treatment for obesity, lead to distinctive changes in weight-loss maintenance and glycaemia. We previously showed that Roux-en-Y Gastric Bypass (RYGB) and Very-Low-Calorie-Diet (VLCD) were superior in weight-loss, compared to a tripeptide hormone infusion of G lucagon-like Peptide-1, O xyntomodulin and P eptide-YY over a month (GOP, infused at doses to replicate their peak post-prandial concentrations as seen at 1 month after RYGB). However, better glycaemic improvement with superior glucose variability attenuation were observed with GOP (1). Bile acids (BA) are important mediators of energy and glucose metabolism. The aims of this study are to investigate the acute and long-term changes in BA metabolism post-RYGB, relative to other weight-loss interventions and to correlate with metabolic improvement.

Methods: Obese participants with type 2 diabetes/pre-diabetes underwent RYGB or a VLCD or were randomised to GOP infusion. Fasted and post-prandial BA and FGF-19 were measured following a mixed meal test, at baseline and 1-month after all 3 interventions, and additionally at 2-3 years post-surgery. Fifteen plasma BA fractions were measured using a liquid chromatography-tandem mass spectrometry. A mixed-effects analysis with Bonferroni correction was applied for within-group comparison.

Results: Study subjects were well matched for baseline characteristics. Changes in weight, fructosamine and fasting BAs are described below:

At 1-month, fasting and post-prandial BA remained statistically unchanged after RYGB and VLCD, but there was a significant reduction in total and other BA parameters with GOP. Post-prandial FGF-19 concentrations decreased with GOP, but no significant change was noted from baseline after RYGB and VLCD at 1-month. However, at 2-3 years post-RYGB, there were significant increases in post-prandial total BAs and the 12 hydroxylated: 12 non-hydroxylated BA ratio, as well as an increase in post-prandial FGF-19 concentrations were observed.

Conclusion: Different weight-loss interventions have distinctive effects on the BA/FGF-19 axis. Despite its lowering effect on several BA fractions and FGF-19 concentrations, significant weight loss and improvement in glycaemia were still observed following a tripeptide gut hormone infusion. Total post-prandial BAs and FGF-19 were only increased at 2-3 years post-RYGB, suggesting a potential role in the long-term rather than short-term efficacy of RYGB.

1. doi: 10.2337/dc19-0449.