Influence of Glucagon Inhibition in Relation to the Anti-Diabetic Effect of Glucagon-Like Peptide-1 (GLP-1) in Patients With Type 2 Diabetes Mellitus

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
University of Copenhagen
Hvidovre University Hospital
Glostrup University Hospital, Copenhagen
Information provided by:
University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT00655603
First received: April 4, 2008
Last updated: April 3, 2009
Last verified: April 2009
  Purpose

Incretinbased treatment of patients with type 2 diabetes mellitus (T2DM) has increasing interest. The incretin glucagon-like peptide-1 (GLP-1) stimulates beta-cells to increased secretion and production of insulin. Glucose sensitivity is enhanced, apoptosis inhibited - progression in disease is potentially stopped. The alpha-cell is also influenced by GLP-1 as infusion lowers plasmaglucose (PG) levels in patients with type 1 diabetes mellitus (T1DM) (C-peptide negative) by inhibition of glucagon and thereby decreased hepatic glucoseproduction (HGP). Further Vilsboll et al has proved normalization of the glacgonostatic effect of glucose in patients with T2DM. As an attempt to elucidate glucose-intolerance in patients with T2DM further Knop et al investigated the glucagonresponse to both oral glucose tolerance test (OGTT) and a following iso-glycemic clamp. He saw a sufficient suppression of glucagon when glucose was introduced intravenously but the suppression of glucagon was attenuated and delayed when glucose was given orally.

The aim of this study is to elucidate the glucose intolerance further. Due to the complex interactions and mutual feed-back regulation between the pancreatic hormones and the PG level this protocol includes five days. All days include a euglycemic-clamp, patients with T2DM (n=10) are clamped at their fasting PG as are healthy control subjects (n=10). During the clamp either GLP-1 alone; GLP-1 in combination with somatostatin, insulin and glucagon; or somatostatin, insulin and glucagon are infused and blood samples are drawn.

The design of the study makes it possible to isolate the effect of each hormone. Further the investigators will be able to enlighten the effect of GLP-1 on the increase in glucose turn-over it induces.

The essential part in this design will be hormone concentrations and the response parameter the amount of glucose (AUC) it takes to create the euglycemic-clamp.


Condition Intervention
Type 2 Diabetes Mellitus
Other: Infusion of native hormones from the pancreas and gut (GLP-1)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Influence of Glucagon Inhibition in Relation to the Anti-Diabetic Effect of GLP-1 in Patients With Type 2 Diabetes Mellitus.

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • Glucose turn-over [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The inhibitory effect of GLP-1 on glucagon, and the role of this in its anti-diabetic potential, measured by looking at glucose turn-over. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: March 2008
Estimated Study Completion Date: September 2009
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
10 patients with Type 2 Diabetes Mellitus
Other: Infusion of native hormones from the pancreas and gut (GLP-1)
Glucose-clamps at fasting levels during infusion of hormones in different combinations.
Experimental: 2
10 healthy, matched control participants
Other: Infusion of native hormones from the pancreas and gut (GLP-1)
Glucose-clamps at fasting levels during infusion of hormones in different combinations.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Type 2 Diabetes Mellitus according to criteria from WHO
  • Normal hepatic and kidney function
  • No overt diabetic complications
  • Treatment with insulin or glitazones
  • Informed consent

Exclusion Criteria:

  • BMI < 23
  • BMI > 35
  • HbA1c > 10%
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Kristine Juul Hare/MD, Gentofte University Hospital, Copenhagen
ClinicalTrials.gov Identifier: NCT00655603     History of Changes
Other Study ID Numbers: H-C-2007-0072
Study First Received: April 4, 2008
Last Updated: April 3, 2009
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University Hospital, Gentofte, Copenhagen:
GLP-1
Glucagon secretion
Glucose turn-over

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hormones
Glucagon
Hypoglycemic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014