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

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Insulin Resistance; Glucose Intolerance

Treatments: Drug: Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT00784745

H-D-2008-087

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 20 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

21 participants in 1 patient group

Dexamethasone

Experimental group

Treatment:

Drug: Dexamethasone