Is Insulin Resistance and/or Glucose Intolerance Pathogenetic in the Development of a Reduced Incretin Effect

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kasper Aaboe, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT00784745
First received: November 3, 2008
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to examine whether there is a causal relationship between insulin resistance and/or glucose intolerance in the development of a defect incretin effect.


Condition Intervention
Insulin Resistance
Glucose Intolerance
Drug: Dexamethasone

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Is Insulin Resistance and/or Glucose Intolerance Pathogenetic in the Development of a Reduced Incretin Effect

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • Incremental GLP-1 response during the mixed meal test. Assessed as AUC during the 4 hour test. [ Time Frame: 4 hours (during the mixed meal test) ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: November 2008
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexamethasone Drug: Dexamethasone
2mg morning and night for 5 days.

Detailed Description:

In this study we are going to examine the incretin effect before and after the development of insulin resistance and/or glucose intolerance. The incretin effect is the increased insulin response seen after an oral as apposed to an intravenous glucose challenge with identical plasma glucose profiles. This insulin enhancing effect is greatly reduced in type 2 diabetes.

Since the development of type 2 diabetes is preceded by insulin resistance and glucose intolerance we wanted to examine the incretin effect in the early stages of type 2 diabetes.

To do this, we want to induce insulin resistance and/or glucose intolerance. This is achieved by 5 days of treatment with dexamethasone.

The incretin effect in this study will be examined by 3 investigations prior to the treatment and 3 days following the treatment.

Day 1: Oral glucose challenge with 75 g of glucose.

The subject is asked to drink 75g of glucose suspended in 300mL of water. During the 4 hours of the test, we draw blood at various times during the study to determine the concentration of: Glucose, GLP-1, GIP, Glucagon, Insulin and c-peptide.

Day 2: Intravenous glucose

We duplicate the glucose curve obtained from day 1. We also draw blood during this test to the same end as in day 1.

Day 3: Mixed meal.

The subjects are served a mixed meal. During this 4 hour test, we draw blood to examine the response to a standardized meal. The test involves sampling blood as described for the other days.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Caucasians >20 years
  • Normal glucose tolerance as assessed by the WHO criteria
  • First degree relative and at least 1 second degree relative with type 2 diabetes
  • Normal haemoglobin
  • Informed consent

Exclusion Criteria:

  • Liver disease (ALAT/ASAT > 2 times normal value)
  • Kidney disease (S-creatinin > 130uM and/or albuminuria)
  • Heart disease (NYHA II, III or IV)
  • Treatment with medicine that cannot be paused
  • Pregnancy of breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784745

Locations
Denmark
Bispebjerg Hospital
Copenhagen, Denmark, 2300
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
Principal Investigator: Thure Krarup, dr. med. Bispebjerg Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kasper Aaboe, Doctor, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT00784745     History of Changes
Other Study ID Numbers: H-D-2008-087
Study First Received: November 3, 2008
Last Updated: May 19, 2014
Health Authority: Denmark: Ethics Committee

Keywords provided by University Hospital, Gentofte, Copenhagen:
incretin effect
type 2 diabetes
GLP-1
GIP
dexamethasone

Additional relevant MeSH terms:
Insulin Resistance
Glucose Intolerance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hyperglycemia
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Incretins
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014