GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia

November 27, 2013 updated by: Asger Lund, Herlev Hospital

The Role of GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia

In order to investigate the mechanisms underlying the hyperglucagonemia characterizing patients with type 2 diabetes mellitus (T2DM) we wish to test the following hypothesis: Do pancreatic alpha-cells exhibit inappropriate glucagon responses to substances released from the small intestine (GIP, GLP-2 and GLP-2) in patients with T2DM?

Study Overview

Detailed Description

Patients with T2DM are not able to suppress their secretion of glucagon after a meal or after oral ingestion of glucose. Patients actually respond with pathological high plasmaglucagon concentrations to these stimuli. Previous studies have shown that postprandial hyperglucagonemia results in increased hepatic glucose production and therefore contributes significantly to the hyperglycemia characterizing these patients.

Recently we have shown that patients with T2DM exhibit a normal suppression of glucagon secretion following an adjustable intravenous (iv) glucose challenge mimicking the glucose excursion following a 50-g oral glucose tolerance test (OGTT) with the latter resulting in lack of glucagon suppression. Why this difference? A possible explanation could be that the oral administration stimulates intestinal factors resulting in a differentially glucagon response to the two similar glucose excursions. We wish to establish whether GIP, GLP-1 and/or GLP-2 are responsible for the inappropriate glucagon suppression following OGTT and meals in patients with T2DM.

Study Type

Observational

Enrollment (Actual)

10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Herlev, Denmark, 2730
        • Department of Endocrinology J, Herlev Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

33 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The patients will be recruted from the outpatient clinic of Department of Endocrinology, Herlev Hospital.

Description

Inclusion Criteria:

  • Caucasians with diet and/or tablet treated T2DM of at least 3 months duration (diagnosed according to the criterias of the World Health Organization (WHO))
  • Normal Hemoglobin
  • Prior Informed Consent

Exclusion Criteria:

  • Liver disease (ALAT/ASAT > 2 x upper normal value)
  • Diabetic nephropathy (se-creatinin > 130 um and/or albuminuria
  • Treatment with drugs that cannot be discontinued for 12 hours

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
A:
Patients with type 2 diabetes mellitus

Day A: Oral glucose tolerance test (50g glucose)

Day B: Isoglycemic intravenous (iv) glucose infusion

Day C: Isoglycemic iv glucose infusion + iv GIP infusion (0-20 min: 4 pmol/kg body weight/min; 20-50 min: 2 pmol/kg body weight/min)

Day D: Isoglycemic iv glucose infusion + iv GLP-1 infusion (0-20 min: 0,6 pmol/kg body weight/min; 20-50 min: 0,3 pmol/kg body weight/min)

Day E: Isoglycemic iv glucose infusion + iv GLP-2 infusion (0-20 min: 1 pmol/kg body weight/min; 20-50 min: 0,5 pmol/kg body wight/min)

Day F: Isoglycemic iv glucose infusion + iv infusion of GIP, GLP-1 and GLP-2 in doses as Day C, D and E.

Other Names:
  • Human GIP (glucose-dependent insulinotropic polypeptide)
  • Human GLP-1 (glucagon-like peptide-1)
  • Human GLP-2 (glucagon-like peptide-2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Plasma glucagon responses
Time Frame: 3 hours
3 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: Tina Vilsbøll, MD DMSc, Herlev Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

July 10, 2008

First Submitted That Met QC Criteria

July 14, 2008

First Posted (Estimate)

July 16, 2008

Study Record Updates

Last Update Posted (Estimate)

November 28, 2013

Last Update Submitted That Met QC Criteria

November 27, 2013

Last Verified

April 1, 2009

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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