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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00497133
Recruitment Status : Completed
First Posted : July 6, 2007
Last Update Posted : June 4, 2008
Novo Nordisk A/S
The Danish Diabetes Association
Information provided by:
University of Copenhagen

July 5, 2007
July 6, 2007
June 4, 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 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 Model: Case Control
Time Perspective: Prospective
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Retention:   Samples With DNA
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 Identifier (NCT Number) in Medline.
Same as current
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
Sexes Eligible for Study: All
40 Years to 75 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
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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