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
1 other identifier
interventional
20
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable type-2-diabetes-mellitus
Started Mar 2008
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2008
CompletedFirst Submitted
Initial submission to the registry
April 4, 2008
CompletedFirst Posted
Study publicly available on registry
April 10, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2009
CompletedApril 6, 2009
April 1, 2009
1.2 years
April 4, 2008
April 3, 2009
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Glucose turn-over
12 months
Secondary Outcomes (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.
12 months
Study Arms (2)
1
EXPERIMENTAL10 patients with Type 2 Diabetes Mellitus
2
EXPERIMENTAL10 healthy, matched control participants
Interventions
Glucose-clamps at fasting levels during infusion of hormones in different combinations.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- BMI \< 23
- BMI \> 35
- HbA1c \> 10%
- Pregnancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital, Gentofte, Copenhagenlead
- University of Copenhagencollaborator
- Hvidovre University Hospitalcollaborator
- Glostrup University Hospital, Copenhagencollaborator
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
April 4, 2008
First Posted
April 10, 2008
Study Start
March 1, 2008
Primary Completion
May 1, 2009
Study Completion
September 1, 2009
Last Updated
April 6, 2009
Record last verified: 2009-04