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

April 3, 2009 updated by: University Hospital, Gentofte, Copenhagen

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Glucose turn-over
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Gentofte, Copenhagen

Collaborators

University of Copenhagen
Hvidovre University Hospital
Glostrup University Hospital, Copenhagen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Anticipated)

May 1, 2009

Study Completion (Anticipated)

September 1, 2009

Study Registration Dates

First Submitted

April 4, 2008

First Submitted That Met QC Criteria

April 4, 2008

First Posted (Estimate)

April 10, 2008

Study Record Updates

Last Update Posted (Estimate)

April 6, 2009

Last Update Submitted That Met QC Criteria

April 3, 2009

Last Verified

April 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-C-2007-0072

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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