Clinical trial NCT00497133: Alpha-Cell Sensitivity to GLP-1 in Patients With Type 2 Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Keywords: glucoseintolerance
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: The Danish Diabetes Association
First posted: 2007-07-06
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Study population: Patients with type 2 diabetes mellitus and matched control subjects.

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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Gentofte Hostital, Dep. og Internal Medicin F
state: Hellerup
Study officials:
affiliation: University of Copenhagen, Department of Biomedical Sciences
name: Jens Juul Holst, Professor, MD,MMSc
role: STUDY_DIRECTOR
References: