Alpha-Cell Sensitivity to GLP-1 in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborators:
Novo Nordisk A/S
The Danish Diabetes Association
Information provided by:
University of Copenhagen
ClinicalTrials.gov Identifier:
NCT00497133
First received: July 5, 2007
Last updated: June 3, 2008
Last verified: June 2008
  Purpose

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.


Condition
Type 2 Diabetes Mellitus

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Biospecimen Retention:   Samples With DNA

Blood for further analyzes and buffy coat


Estimated Enrollment: 20
Study Start Date: July 2007
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Study Population

Patients with type 2 diabetes mellitus and matched control subjects.

Criteria

Inclusion Criteria:

  • Informed oral and written consent
  • Caucasians aged > 18 years diagnosed with T2DM due to WHO criteria.
  • Normal haemoglobin
  • HbA1c 6-10%
  • BMI 23-35 kg/m2

Exclusion Criteria:

  • Hepatic disease, ALAT > 2 x normal.
  • Diabetic nephropathy, (S-creatinine >130μM or albuminuria).
  • Diabetic neuropathy (reported)
  • Proliferative diabetic retinopathy (reported)
  • Medical treatment that cannot be paused for 12 hours
  • Insulin- or glitazon treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00497133

Locations
Denmark
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
  More Information

No publications provided

Responsible Party: K. J. Hare, Gentofte University Hospital, University of Copenhagen.
ClinicalTrials.gov Identifier: NCT00497133     History of Changes
Other Study ID Numbers: H-KA-20070023
Study First Received: July 5, 2007
Last Updated: June 3, 2008
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University of Copenhagen:
glucoseintolerance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014