Dissection of the Gastrointestinal-mediated Glucose Disposal and Incretin Defect in Patients With Type 2 Diabetes
Status:
Completed
Trial end date:
2016-08-01
Target enrollment:
Participant gender:
Summary
In patients with type 2 diabetes, the incretin effect is markedly reduced contributing to the
relative insulin deficiency that characterizes these patients. This defect is believed to be
due to a decreased effect of GLP-1 and an almost ceased effect of GIP. Nevertheless, the
impact of the defect on glucose tolerance is not fully understood. The so-called
gastrointestinal-mediated glucose disposal (GIGD) is a measure of glucose handling, which
includes the incretin effect, but also other factors affecting glucose disposal (e.g.
glucagon secretion). Interestingly, patients with type 2 diabetes exhibit elevated plasma
glucagon levels in the fasting state, and glucagon concentrations fail to decrease
appropriately and may even increase in response to ingestion of glucose and show exaggerated
increases after a mixed meal. With the current project the investigators wish to elucidate
how this paradoxical glucagon response observed in patients with type 2 diabetes affects the
GIGD, the incretin effect and postprandial glucose excursions.
Ten patients with type 2 diabetes and 10 healthy matched control subjects will be enrolled in
this randomised, placebo-controlled, double-blinded study. The aim is to examine the effect
of a glucagon receptor antagonist (GRA) on gastrointestinal-mediated glucose disposal (GIGD),
incretin effect and postprandial glucose excursions in patients with type 2 diabetes and
healthy controls. Participants will attend two oral glucose tolerance tests (OGTT), two
isoglycaemic iv glucose infusion (IIGI) and two standardised liquid meals.