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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Purpose
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 | Intervention |
|---|---|
|
Type 2 Diabetes Mellitus |
Other: Infusion of native hormones from the pancreas and gut (GLP-1) |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Single Group Assignment Masking: Single Blind (Subject) 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. |
- Glucose turn-over [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | March 2008 |
| Estimated Study Completion Date: | September 2009 |
| Estimated Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations More Information
No publications provided
| 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 |
| Study First Received: | April 4, 2008 |
| Last Updated: | April 3, 2009 |
| Health Authority: | Denmark: The Regional Committee on Biomedical Research Ethics |
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 Glucagon Glucagon-Like Peptide 1 Hormones |
Hypoglycemic Agents Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Gastrointestinal Agents Therapeutic Uses Incretins |
ClinicalTrials.gov processed this record on May 16, 2013