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. 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 has been shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) bile acid sequestration 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
15
Center for Diabetes Research
Hellerup, Denmark
Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Blood analysis of paracetamol as an assessment of gastric emptying
Assessment of gastric emptying
Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Indirect calorimetry: Basal metabolic rate
Basal metabolic rate
Time frame: -30 min to 240 min
Gallbladder volume as assessed by Ultrasound measurements
Gallbladder volume
Time frame: -30 min to 240 min
Appetite as assessed by Visual analog scale score
Appetite
Time frame: -30 min to 240 min
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