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

NCT ID: NCT00784745

Last Updated: 2014-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2009-09-30

Brief 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.

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.

Conditions

Insulin Resistance; Glucose Intolerance

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

Dexamethasone

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

2mg morning and night for 5 days.

Interventions

Dexamethasone

2mg morning and night for 5 days.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Kasper Aaboe

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thure Krarup, dr. med.

Role: PRINCIPAL_INVESTIGATOR

Bispebjerg Hospital

Locations

Bispebjerg Hospital

Copenhagen, , Denmark

Countries

Denmark

References

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. doi: 10.1007/s001250050847.

Reference Type: BACKGROUND

PMID: 9447952 (View on PubMed)

Jensen DH, Aaboe K, Henriksen JE, Volund A, Holst JJ, Madsbad S, Krarup T. Steroid-induced insulin resistance and impaired glucose tolerance are both associated with a progressive decline of incretin effect in first-degree relatives of patients with type 2 diabetes. Diabetologia. 2012 May;55(5):1406-16. doi: 10.1007/s00125-012-2459-7.

Reference Type: DERIVED

PMID: 22286551 (View on PubMed)

Other Identifiers

H-D-2008-087

Identifier Type: -

Identifier Source: org_study_id