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

Herlev Hospital

Status: Completed

Conditions: Type 2 Diabetes Mellitus

Treatments: Biological: Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)

Study type: Observational

Funder types: Other

Identifiers

NCT00716170

1301831410

Details and patient eligibility

About

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?

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 35+ years old

Volunteers: No Healthy Volunteers

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

Trial design

10 participants in 1 patient group

A:

Description:

Patients with type 2 diabetes mellitus

Treatment:

Biological: Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)