Insulinotropic Effect of GLP-1 and GIP After Dexamethasone

Study Overview
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Brief Summary
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In this study we examine whether inducing insulin resistance by dexamethasone in healthy volunteers will lead to a decreased insulinotropic effect of the hormones GLP-1 and GIP.

Detailed Description
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In this study we are going to examine the insulinotropic properties of GLP-1 and GIP before and after the development of insulin resistance and/or glucose intolerance.The insulinotropic properties of GLP-1 and GIP are 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 insulinotropic properties of GLP-1 and GIP 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. Subjects are studied on 4 different days in randomized order, with an oral glucose tolerance test (OGTT) and glucose clamps + infusions of GLP-1, GIP and NaCl before and immediately after 5 days treatment with dexamethasone, 2mg bid. On day 1, 2 and 3 after the 5 days of dexamethasone, 2mg dexamethasone was given in the afternoon after the tests to ensure unchanged insulin resistance

Official Title
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Loss of Insulinotropic Properties of Glucagon-like Peptide-1 (GLP-1) and Glucose-dependent Insulinotropic Peptide (GIP) After Glucocorticoid Induced Insulin Resistance

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasians above 20 and below 45 years of age 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone<br>This is a before-after study. All subjects are administered dexamethasone 2mg BID for 5 days. | Drug: Dexamethasone<br>* Dexamethasone are given dexamethasone tablets of 2mg twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The potentiating effects of GLP-1 on second phase insulin response when clamped at at bloodsugar of 7 mmol/l | After dexamethasone treatment subjects are tested with infusion of GLP-1 during a clamped blood-sugar of 7mmol/l. Their increase in the second phase insulin response is the primary endpoint. | 1-3 days after dexamethasone treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First phase insulin response to GLP-1 infusion at 7mmol/l |  | 1-3 days after dexamethasone | 
| First phase insulin response to GIP infusion at 7mmol/l |  | 1-3 days after dexamethasone | 
| Second phase insulin response to GIP infusion at 7mmol/l |  | 1-3 days after dexamethasone treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GIP, Incretin hormones, GLP-1, Dexamethasone