NCT00716170

GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia

The Role of GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 10 (actual)
• Sponsor: Herlev Hospital · Academic / Other
• Sex: All
• Age: 35 Years
• Healthy volunteers: Not accepted

Summary

In order to investigate the mechanisms underlying the hyperglucagonemia characterizing patients with type 2 diabetes mellitus (T2DM) we wish to test the following hypothesis: Do pancreatic alpha-cells exhibit inappropriate glucagon responses to substances released from the small intestine (GIP, GLP-2 and GLP-2) in patients with T2DM?

Detailed description

Patients with T2DM are not able to suppress their secretion of glucagon after a meal or after oral ingestion of glucose. Patients actually respond with pathological high plasmaglucagon concentrations to these stimuli. Previous studies have shown that postprandial hyperglucagonemia results in increased hepatic glucose production and therefore contributes significantly to the hyperglycemia characterizing these patients. Recently we have shown that patients with T2DM exhibit a normal suppression of glucagon secretion following an adjustable intravenous (iv) glucose challenge mimicking the glucose excursion following a 50-g oral glucose tolerance test (OGTT) with the latter resulting in lack of glucagon suppression. Why this difference? A possible explanation could be that the oral administration stimulates intestinal factors resulting in a differentially glucagon response to the two similar glucose excursions. We wish to establish whether GIP, GLP-1 and/or GLP-2 are responsible for the inappropriate glucagon suppression following OGTT and meals in patients with T2DM.

Conditions

• Type 2 Diabetes Mellitus

Interventions

Type	Name	Description
BIOLOGICAL	Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)	Day A: Oral glucose tolerance test (50g glucose) Day B: Isoglycemic intravenous (iv) glucose infusion Day C: Isoglycemic iv glucose infusion + iv GIP infusion (0-20 min: 4 pmol/kg body weight/min; 20-50 min: 2 pmol/kg body weight/min) Day D: Isoglycemic iv glucose infusion + iv GLP-1 infusion (0-20 min: 0,6 pmol/kg body weight/min; 20-50 min: 0,3 pmol/kg body weight/min) Day E: Isoglycemic iv glucose infusion + iv GLP-2 infusion (0-20 min: 1 pmol/kg body weight/min; 20-50 min: 0,5 pmol/kg body wight/min) Day F: Isoglycemic iv glucose infusion + iv infusion of GIP, GLP-1 and GLP-2 in doses as Day C, D and E.

Timeline

• Start date: 2008-07-01
• Primary completion: 2009-07-01
• Completion: 2009-07-01
• First posted: 2008-07-16
• Last updated: 2013-11-28

Locations

1 site across 1 country: Denmark