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

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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Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Gentofte Hostital, Dep. og Internal Medicin F

Gentofte Municipality, Hellerup, DK-2900, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Sponsors and collaborators

Lead sponsor

University of Copenhagen

Other

Collaborators

Novo Nordisk A/S
The Danish Diabetes Association

Registry information

Important dates

Study start: 2007
Primary completion: 2008
Study completion: 2008
First posted: Jul 6, 2007
Registry last updated: Jun 4, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed