Type 2 Diabetes
Conditions
Keywords
Incretin hormones, GLP-1, GIP, Dexamethasone
Brief summary
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
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
Interventions
Dexamethasone are given dexamethasone tablets of 2mg twice daily.
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The potentiating effects of GLP-1 on second phase insulin response when clamped at at bloodsugar of 7 mmol/l | 1-3 days after dexamethasone treatment | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Second phase insulin response to GIP infusion at 7mmol/l | 1-3 days after dexamethasone treatment |
| 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 |
Other
| Measure | Time frame |
|---|---|
| Total insulin response to arginine infusion | 1-3 days after dexamethasone |
Countries
Denmark