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

This study has been completed.
Sponsor:
Collaborators:
University of Copenhagen
The Danish Medical Research Council
The Danish Diabetes Association
Information provided by:
Herlev Hospital
ClinicalTrials.gov Identifier:
NCT00716170
First received: July 10, 2008
Last updated: February 24, 2010
Last verified: April 2009

July 10, 2008
February 24, 2010
July 2008
July 2009   (final data collection date for primary outcome measure)
Plasma glucagon responses [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00716170 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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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

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?

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.

Observational
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Not Provided
Retention:   Samples With DNA
Description:

Blood plasma and leucocytes

Non-Probability Sample

The patients will be recruted from the outpatient clinic of Department of Endocrinology, Herlev Hospital.

Type 2 Diabetes Mellitus
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.

Other Names:
  • Human GIP (glucose-dependent insulinotropic polypeptide)
  • Human GLP-1 (glucagon-like peptide-1)
  • Human GLP-2 (glucagon-like peptide-2)
A:
Patients with type 2 diabetes mellitus
Intervention: Biological: Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
July 2009
July 2009   (final data collection date for primary outcome measure)

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
Both
35 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00716170
1301831410
Yes
Tina Vilsbøll/ MD DMSc, Herlev Hospital
Herlev Hospital
  • University of Copenhagen
  • The Danish Medical Research Council
  • The Danish Diabetes Association
Study Chair: Tina Vilsbøll, MD DMSc Herlev Hospital
Study Director: Filip K Knop, MD PhD Gentofte Hospital
Herlev Hospital
April 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP