Background: Increased circulating bile acids may contribute to improved glucose control and augmented secretion of the gut hormones peptide tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1) observed post-prandially in patients following bariatric surgery. Oral bile acids could represent a non-surgical means of improving glucose tolerance after a meal.
Aim: To investigate the effects of a single oral dose of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on glucose homeostasis and gut hormone secretion post-prandially.
Methods: In a randomised placebo-controlled cross-over study, twelve healthy volunteers ingested no bile acid, UDCA or CDCA at 1316 mg/kg 60 min prior to consuming a milkshake meal (700 kcal). Peripheral blood samples were taken at intervals and gut hormones were assayed from plasma using radioimmunoassay or commercial ELISA kits. Area under the curve (AUC) was calculated using the trapezoid rule, with baseline as y=0, and compared with repeated measures one-way ANOVA with GeisserGreenhouse correction.
Results: Ingestion of either bile acid attenuated the post-prandial rise in insulin and was associated with an increase in PYY. CDCA was also associated with an increase in GLP-1 and a reduction in glucose dependent insulinotropic polypeptide (GIP).
|Glucose mmol/l·min||1487 (40.6)||1413 (52.5)||1453 (45.4)|
|Insulin μU/ml· min||9682 (1630)||7278 (1040)||6174 (883)*|
|Insulin: glucose ratio||1812 (273)||1406 (189)*||1228 (154)*|
|GLP-1 total pmol/l·min||1517 (243)||1596 (275)||2166 (332)**|
|PYY pmol/l·min||675.4 (131)||990.9 (176)*||1490 (299)*|
|GIP pmol/l·min||31693 (5000)||30774 (7320)||22128 (4460)*|
|Changes in Area Under the Curve (AUC) when compared with no bile acid; *P<0.05; **P<0.001|
Conclusions: Before a meal, oral exogenous CDCA improves indices of insulin sensitivity and increases levels of GLP-1 and PYY. CDCA is a possible adjunctive treatment of treatment of type 2 diabetes and further trials are required.