Diabetes Mellitus, Type 2 Clinical Trial
Accumulating evidence suggests that bile acids in our intestines may constitute essential
components in the complex mechanisms regulating gut hormone secretion and glucose
homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile
acids can lead to changes in gut hormone secretion and consequently affect glucose
homeostasis.
The current study is a human interventional randomized controlled cross-over study including
four study days for each participant. Metformin will be applied as a tool to reduce bile
acid reuptake in the small intestine; thereby increasing bile acid concentration in the more
distal parts of the gut where GLP-1-secreting L cell are abundant. Interestingly, metformin
has been shown to reduce the active reabsorption of bile acids in the ileum and cause
increased faecal elimination of bile acids. Clinical data has suggested that metformin
causes an increase in the postprandial secretion of GLP-1 in humans including patients with
type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder
contraction and emptying. The aim is to examine how (and if) modification of bile acid
reabsorption can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and
glucose homeostasis in patients with type 2 diabetes.
The investigators hypothesize that higher luminal concentrations of bile acids in the distal
gut will elicit changes in gut hormone secretion. 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 and glucose metabolism.
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