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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

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ClinicalTrials.gov Identifier: NCT00655603
Recruitment Status : Unknown
Verified April 2009 by University Hospital, Gentofte, Copenhagen.
Recruitment status was:  Enrolling by invitation
First Posted : April 10, 2008
Last Update Posted : April 6, 2009
Sponsor:
Collaborators:
University of Copenhagen
Hvidovre University Hospital
Glostrup University Hospital, Copenhagen
Information provided by:
University Hospital, Gentofte, Copenhagen

Brief Summary:

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 or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Other: Infusion of native hormones from the pancreas and gut (GLP-1) Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Participant)
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.
Study Start Date : March 2008
Estimated Primary Completion Date : May 2009
Estimated Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones
Drug Information available for: Glucagon
U.S. FDA Resources

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Glucose turn-over [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. 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 ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

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
First Posted: April 10, 2008    Key Record Dates
Last Update Posted: April 6, 2009
Last Verified: April 2009

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

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hormones
Glucagon
Glucagon-Like Peptide 1
Pancrelipase
Hypoglycemic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents
Incretins