Effect of Bile Acid Sequestration on Postprandial GLP-1 Secretion, Glucose Homeostasis and Gut Microbiota
Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
Participant gender:
Summary
Accumulating evidence suggests that bile acids and bacteria in our intestines may constitute
essential components in the complex mechanisms regulating gut hormone secretion and glucose
homeostasis. At the same time, bile acids and gut bacteria are interdependent. Thus, it is
likely that modification of the enterohepatic circulation of bile acids can lead to changes
in gut hormone secretion or gut bacteria composition and consequently affect glucose
homeostasis.
The current study is a human interventional study with 7-day ingestion of a bile acid
sequestrant or placebo, preceded and followed by meal tests and faecal sampling. The aim is
to examine how (and if) bile acid sequestration can influence postprandial glucagon-like
peptide-1 (GLP-1) secretion, gut microbiota and glucose homeostasis in patients with type 2
diabetes and healthy individuals. As a tool to sequester bile acids we will use sevelamer, a
phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with
chronic kidney disease. Surprisingly, sevelamer was recently shown to improve glycaemic
control in patients with chronic kidney disease and type 2 diabetes.
The investigators hypothesize that higher luminal concentrations of bile acids in the distal
gut will elicit changes in the postprandial gut hormone secretion and gut bacteria
composition. The current study will help to clarify this hypothesis and improve our general
understanding of the association between bile acid circulation and signalling, gut hormone
secretion, gut bacteria and glucose metabolism.