Insulinotropic Effect of GLP-1 and GIP After Dexamethasone

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

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.

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

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