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

July 5, 2007
June 3, 2008
July 2007
March 2008   (final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00497133 on ClinicalTrials.gov Archive Site
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Alpha-Cell Sensitivity to GLP-1 in Patients With Type 2 Diabetes
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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.

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.

Observational
Observational Model: Case Control
Time Perspective: Prospective
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Retention:   Samples With DNA
Description:

Blood for further analyzes and buffy coat

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Patients with type 2 diabetes mellitus and matched control subjects.

Type 2 Diabetes Mellitus
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
March 2008
March 2008   (final data collection date for primary outcome measure)

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
Both
40 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00497133
H-KA-20070023
No
K. J. Hare, Gentofte University Hospital, University of Copenhagen.
University of Copenhagen
  • Novo Nordisk A/S
  • The Danish Diabetes Association
Study Director: Jens Juul Holst, Professor, MD,MMSc University of Copenhagen, Department of Biomedical Sciences
University of Copenhagen
June 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP