Alpha-Cell Sensitivity to GLP-1 in Patients With Type 2 Diabetes
Study Details
Study Description
Brief Summary
Glucagon-like peptide 1 is known to improve sensitivity of the pancreatic beta-cell. Further it inhibit secretion from the pancreatic alpha-cell by mechanisms not fully understand. With this study we wish to elucidate the potential of GLP-1 to increase the sensitivity of the alpha-cell.
Type 2 diabetic patients and control subjects receive infusions of GLP-1 in increasing doses or saline, alpha- and beta-cell responses are measured in blood-samples. During the study plasma-glucose levels are clamped at fasting levels.
With this study we hope to elucidate the pathophysiology behind defect glucose tolerance in type 2 diabetes mellitus and further more the potential of GLP-1 in treatment of type 2 diabetes mellitus.
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Detailed Description
Background: Glucagon-like peptide-1 (GLP-1) possesses insulinotropic and glucagonostatic properties, and, therefore, GLP-based antidiabetic therapies have been developed. Even though the insulinotropic potency of GLP-1 has been shown to be reduced in patients with type 2 diabetes mellitus (T2DM), a small dose of GLP-1 is capable of normalizing the beta-cell responsiveness to glucose in these patients. The glucagonostatic potency of GLP-1 in patients with T2DM is not known, and, furthermore, the capability of GLP-1 to reestablish normal glucagon secretion in these patients remains to be elucidated.
Objective: To investigate the alpha-cell sensitivity to GLP-1 in patients with T2DM and to establish if GLP-1 is able to reestablish normal glucagon secretion in such patients.
Method: Ten patients with T2DM and ten healthy control subjects are clamped at their fasting blood glucose levels during GLP-1 infusions at increasing doses (0.25, 0.5, 1.0 and 2.0 pmol/kg/min) and placebo, respectively. Furthermore, the patients will be hospitalized overnight while receiving intravenous insulin and thereafter examined under normoglycaemic conditions. Blood are being drawn for analysis of plasma insulin, C-peptide, GLP-1 and glucagon.
Expected results and conclusions: We expect that GLP-1 will inhibit glucagon secretion in a dose dependent manner, leading too an increase in glucose turn-over. The results will potentially elucidate the interaction between GLP-1 and glucagon secretion and thereby broaden our knowledge on the pathophysiology of T2DM. Furthermore, the present study will determine the therapeutic impact of GLP-1 on the alpha-cell deficiency characterizing patients with T2DM.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
Inclusion Criteria:
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Informed oral and written consent
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Caucasians aged > 18 years diagnosed with T2DM due to WHO criteria.
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Normal haemoglobin
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HbA1c 6-10%
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BMI 23-35 kg/m2
Exclusion Criteria:
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Hepatic disease, ALAT > 2 x normal.
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Diabetic nephropathy, (S-creatinine >130μM or albuminuria).
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Diabetic neuropathy (reported)
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Proliferative diabetic retinopathy (reported)
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Medical treatment that cannot be paused for 12 hours
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Insulin- or glitazon treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
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| 1 | Gentofte Hostital, Dep. og Internal Medicin F | Gentofte | Hellerup | Denmark | DK-2900 |
Sponsors and Collaborators
- University of Copenhagen
- Novo Nordisk A/S
- The Danish Diabetes Association
Investigators
- Study Director: Jens Juul Holst, Professor, MD,MMSc, University of Copenhagen, Department of Biomedical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-KA-20070023