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

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Biological: Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)

• Registration Number: NCT00716170
• Lead Sponsor: Herlev Hospital

Brief 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.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-07-10
• Study First Submitted QC: 2008-07-14
• Study First Posted: 2008-07-16
• Status Verified: 2009-04
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Last Update Submitted: 2013-11-27
• Last Update Posted: 2013-11-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Caucasians with diet and/or tablet treated T2DM of at least 3 months duration (diagnosed according to the criterias of the World Health Organization (WHO))
• Normal Hemoglobin
• Prior Informed Consent

Exclusion Criteria

• Liver disease (ALAT/ASAT > 2 x upper normal value)
• Diabetic nephropathy (se-creatinin > 130 um and/or albuminuria
• Treatment with drugs that cannot be discontinued for 12 hours

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
A:	Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)	Patients with type 2 diabetes mellitus

Primary Outcome Measures

Name	Time	Method
Plasma glucagon responses	3 hours

Trial Locations

Locations (1)

Department of Endocrinology J, Herlev Hospital; 🇩🇰 Herlev, Denmark