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
Information source: University Hospital, Gentofte, Copenhagen
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes Mellitus
Intervention: Infusion of native hormones from the pancreas and gut (GLP-1) (Other)
Status: Active, not recruiting
Sponsored by: University Hospital, Gentofte, Copenhagen
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 we
will be able to enlighten the effect of GLP-1 on the increase in glucose turn-over it
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.
Official title: Influence of Glucagon Inhibition in Relation to the Anti-Diabetic Effect of GLP-1 in Patients With Type 2 Diabetes Mellitus.
Study design: Basic Science, Randomized, Single Blind (Subject), Active Control, Single Group Assignment
Primary outcome: Glucose turn-over
Secondary outcome: 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.
Minimum age: 18 Years.
Maximum age: 70 Years.
- 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
- BMI < 23
- BMI > 35
- HbA1c > 10%
Locations and Contacts
Starting date: March 2008
Ending date: December 2008
Last updated: April 4, 2008