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

Insulin Resistance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00784745
• Other study ID #: H-D-2008-087
• Status: Completed
• Phase: N/A
• First received: November 3, 2008
• Last updated: May 19, 2014
• Start date: November 2008
• Est. completion date: September 2009

Study information

• Verified date: May 2014
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: September 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Glucose Intolerance
• Insulin Resistance

Intervention

Drug:
• Dexamethasone
2mg morning and night for 5 days.

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Henriksen JE, Alford F, Ward GM, Beck-Nielsen H. Risk and mechanism of dexamethasone-induced deterioration of glucose tolerance in non-diabetic first-degree relatives of NIDDM patients. Diabetologia. 1997 Dec;40(12):1439-48. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incremental GLP-1 response during the mixed meal test. Assessed as AUC during the 4 hour test.		4 hours (during the mixed meal test)	No