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

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00716170

Enrollment

Registered

2008-07-16

Start date

2008-07-31

Completion date

2009-07-31

Last updated

2013-11-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes Mellitus, Glucagon, Insulin, Incretin hormones, Glucose-dependent insulinotropic polypeptide, Glucagon-like peptide-1, Glucagon-like peptide-2

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.

Interventions

BIOLOGICALGlucose-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.

Study design

Observational model

CASE_ONLY

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

35 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame
Plasma glucagon responses	3 hours

Countries

Denmark

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026