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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT00655603
• Other study ID #: H-C-2007-0072
• Status: Enrolling by invitation
• Phase: N/A
• First received: April 4, 2008
• Last updated: April 3, 2009
• Start date: March 2008
• Est. completion date: September 2009

Study information

• Verified date: April 2009
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: September 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Other:
• Infusion of native hormones from the pancreas and gut (GLP-1)
Glucose-clamps at fasting levels during infusion of hormones in different combinations.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	Glostrup University Hospital, Copenhagen, Hvidovre University Hospital, University of Copenhagen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucose turn-over		12 months	No
Secondary	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.		12 months	No