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 (Responsible Party):
Asger Lund, Herlev Hospital
ClinicalTrials.gov Identifier:
NCT00716170
First received: July 10, 2008
Last updated: November 27, 2013
Last verified: April 2009
  Purpose

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?


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

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: The Role of GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia

Resource links provided by NLM:


Further study details as provided by Herlev Hospital:

Primary Outcome Measures:
  • Plasma glucagon responses [ Time Frame: 3 hours ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood plasma and leucocytes


Enrollment: 10
Study Start Date: July 2008
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
A:
Patients with 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)

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.

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00716170

Locations
Denmark
Department of Endocrinology J, Herlev Hospital
Herlev, Denmark, 2730
Sponsors and Collaborators
Herlev Hospital
University of Copenhagen
The Danish Medical Research Council
The Danish Diabetes Association
Investigators
Study Chair: Tina Vilsbøll, MD DMSc Herlev Hospital
Study Director: Filip K Knop, MD PhD Gentofte Hospital
  More Information

Publications:

Responsible Party: Asger Lund, MD, Herlev Hospital
ClinicalTrials.gov Identifier: NCT00716170     History of Changes
Other Study ID Numbers: 1301831410
Study First Received: July 10, 2008
Last Updated: November 27, 2013
Health Authority: Denmark: National Board of Health
Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency

Keywords provided by Herlev Hospital:
Diabetes Mellitus
Glucagon
Insulin
Incretin hormones
Glucose-dependent insulinotropic polypeptide
Glucagon-like peptide-1
Glucagon-like peptide-2

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Gastric Inhibitory Polypeptide
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014