Glucagon-Like Peptide-1 (GLP-1) Suppression of Alpha Cell Secretion in Type 2 Diabetes Mellitus (T2DM)

NCT ID: NCT00862589

Last Updated: 2009-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2007-03-31

Brief Summary

The incretin hormone glucagon-like peptide-1 (GLP-1) has known insulinotrophic and glucagonostatic properties. However, inpatients with type 2 diabetes mellitus (T2DM)it is shown, that the beta cell sensitivity towards GLP-1 is decreased, when comparing to healthy controls. Further, these patients have decreased GLP-1 response to a meal.

The aim of this study is to elucidate if the diabetic hyperglucagonemia, seen in these patients both during fasting and in a postprandial condition, is coursed by a decreased sensitivity to GLP-1 in the diabetic alpha cell.

Ten T2DM patients and ten matched healthy control subjects will be examined on two separate days. Day 1: increasing GLP-1 infusions and Day 2: saline. During both days plasma glucose (PG) will be clamped at fasting level (FPG).

Patients with T2DM will be submitted til a Day 3, here PG will be normalized over-night by an adjustable insulin infusion, on the following day the GLP-1 infusion of Day 1 will be repeated.

The hypothesis is that these patients have decreased alpha cell sensitivity to GLP-1 as is the case with the beta cell sensitivity. This decreased sensitivity, the investigators speculate, contributes the defect suppression og glucagon and thereby to the increased PG levels seen in T2DM. Further the investigators will elucidate if this sensitivity can be increased by normalizing the diabetic PG to a normal FPG level.

Conditions

Hyperglycemia; Hyperglucagonemia; Glucose Intolerance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: SINGLE

Interventions

GLP-1 infusion

physiological effect of GLP-1

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• T2DM according to WHO criteria
• Written consent
• Age > 18 years

Exclusion Criteria

• Kidney or hepatic disease
• Treatment with insulin or glitazone

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

University Hospital, Gentofte, Copenhagen

References

Hare KJ, Knop FK, Asmar M, Madsbad S, Deacon CF, Holst JJ, Vilsboll T. Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009 Dec;94(12):4679-87. doi: 10.1210/jc.2009-0921. Epub 2009 Oct 16.

Reference Type: DERIVED

PMID: 19837930 (View on PubMed)

Other Identifiers

H-KA-20070023

Identifier Type: -

Identifier Source: org_study_id