Context: Gastric bypass (GBP) and sleeve gastrectomy (SG) are both effective bariatric treatments that cause sustained weight loss as well as improvement of type 2 diabetes mellitus (T2DM). The underlying mechanisms are under investigation, including the contribution of alterations in bile acids (BAs) in achieving or maintaining the beneficial metabolic effects after bariatric surgery.
Aims: The aim of this study is to investigate the acute and short-term effects of GBP and SG on BA compositions and fibroblast growth factor 19 (FGF19) in obese individuals with T2DM and to evaluate any correlations between changes in these measures with glucose metabolic improvements.
Methods: The levels of both fasting and postprandial plasma BA compositions after oral glucose tolerance test (OGTT), fasting FGF19 and various metabolic indices were measured 1 day before and at 3 days and 3 months after GBP and SG in 19 obese patients (GBP = 8, SG = 11) with T2DM.
Results: Body weight loss was observed after both GBP and SG 3 months post-operatively, with no significant difference between the two intervention groups (15.0 ± 3.1% vs. 13.9 ± 5.2%, P = 0.761). At 3 days post-operation, FGF19 levels increased significantly in both surgery groups (GBP, 118.3 ± 57.3 vs. 363.6 ± 131.0 pg mL-1, post-operation P = 0.008; SG, 173.2 ± 127.8 vs. 422.0 ± 243.6 pg mL-1, post-operation P = 0.001). Fasting and postprandial increases from pre-operative values in secondary (r = 0.57, P = 0.02; r = 0.58, P = 0.01), conjugated (r = 0.50, P = 0.01; r = 0.48, P = 0.04), glycine-conjugated (r = 0.52, P = 0.05; r = 0.46, P = 0.05) and secondary-conjugated (r = 0.53, P = 0.02; r = 0.60, P = 0.01) BAs correlated with decreases in the postprandial states of glucose (defined by area under the curve (AUC) over 120 min (AUC0-120min)). Increases in postprandial primary-conjugated BAs were found to be associated with decreases in HOMA-IR (r = 0.45, P = 0.05). However, increases in fasting and postprandial taurine-conjugated BA correlated with decreases in both basal insulin secretion rate (r = 0.47, P = 0.04; r = 0.48, P = 0.04) and C-peptide level (r = 0.45, P = 0.05; r = 0.47, P = 0.04). After 3 months, fasting and postprandial increases in secondary (r = 0.51, P = 0.03; r = 0.48, P = 0.04), secondary-conjugated (r = 0.52, P = 0.02; r = 0.51, P = 0.03) and non-12α-OH (r = 0.51, P = 0.02; r = 0.58, P = 0.01) BAs were found to correlate with increases in Stumvoll Insulin Sensitivity Index. Increases in both fasting and postprandial 12α-OH BAs were correlated with the decreases in glucose AUC (r = 0.46, P = 0.05; r = 0.41, P = 0.04).
Conclusions: Both GBP and SG achieve increases in many BA species as early as 3 days post-operation, which are sustained at 3 months post-operation. Rises in secondary BA and conjugated forms are correlated with early improvements in glucose metabolism at 3 days post-operation. These along with 12α-OH BA correlated with improved glucose metabolism at 3 months post-operation, suggesting they may contribute to the observed T2DM remission after bariatric surgery.
Keywords: Bile acids; Diabetes; FGF19; Gastric bypass; Sleeve gastrectomy.