The Role of Small Intestinal Endocrine Cells in Type 2 Diabetic Hyperglucagonemia

Completed

• Conditions: Type 2 Diabetes
• Interventions: Procedure: Double-balloon enteroscopy; Other: Standard meal test

• Registration Number: NCT00639613
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

The purpose of this study is to determine whether excessive secretion of glucagon in type 2 diabetes originates from the pancreatic alpha-cells or endocrine cells in the mucosa of the small intestinal.

Detailed Description

Hyperglucagonemia contributes significantly to the hyperglycemia characterizing patients with Type 2 diabetes. Fasting hyperglucagonemia induces hepatic glucose release resulting in elevated fasting levels of plasma glucose. Furthermore, lack of postprandial suppression of glucagon secretion - exchanged for a paradoxical postprandial hypersecretion of glucagon - results in increased levels of postprandial plasma glucose. Additionally, type 2 diabetes is characterized by decreased postprandial responses of the insulinotropic (and glucagonostatic) peptide hormone glucagon-like peptide-1 (GLP-1). Recent studies from our group suggest that the intestines are involved in the diminshed suppression of glucagon following ingestion of nutrients. Thus, suppression of glucagon during oral glucose ingestion diminishes and reverses to stimulation while suppression during intravenous administered glucose sustains along with development of glucose intolerance. In the small intestines mucosal endocrine L-cells secrete GLP-1, which is processed from its precursor, proglucagon, by prohormone convertase 1 (PC1). In the pancreatic alpha-cells proglucagon is processed to glucagon via prohormone convertase 2 (PC2). We plan to examine biopsies from the mucosa of the small intestines from patients with type 2 diabetes and from healthy subjects for glucagon production. Furthermore, the volunteers will be subjected to a standard meal test in order to correlate the gene expression studies with the level of postprandial hyperglucagonemia of the subjects.

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2008-03-12
• Study First Submitted QC: 2008-03-12
• Study First Posted: 2008-03-20
• Status Verified: 2015-06
• Primary Completion: 2015-06
• Last Update Submitted: 2015-06-25
• Last Update Posted: 2015-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Diagnosed with type 2 diabetes for at least 3 months
• Normal hemoglobin
• Informed consent

Exclusion Criteria

• Liver disease (ALAT/ASAT > 2 x normal range)
• Diabetic nephropathy (se-creatinin > 130 µM and/or albuminuriu)
• Treatment with medication that can not be stopped for12 hours

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
2	Standard meal test	Healthy subjects
1	Double-balloon enteroscopy	Patients with type 2 diabetes
1	Standard meal test	Patients with type 2 diabetes
2	Double-balloon enteroscopy	Healthy subjects

Trial Locations

Locations (1)

Department of Internal Medicine F' laboratory; 🇩🇰 Hellerup, Copenhagen County, Denmark