Clinical trial NCT02235584: Insulinotropic Effect of GLP-1 and GIP After Dexamethasone
Official title: Loss of Insulinotropic Properties of Glucagon-like Peptide-1 (GLP-1) and Glucose-dependent Insulinotropic Peptide (GIP) After Glucocorticoid Induced Insulin Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Keywords: Incretin hormones
GLP-1
GIP
Dexamethasone
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2014-09-10
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: The potentiating effects of GLP-1 on second phase insulin response when clamped at at bloodsugar of 7 mmol/l
timeFrame: 1-3 days after dexamethasone treatment
Secondary outcomes:
measure: First phase insulin response to GLP-1 infusion at 7mmol/l
timeFrame: 1-3 days after dexamethasone
measure: First phase insulin response to GIP infusion at 7mmol/l
timeFrame: 1-3 days after dexamethasone
measure: Second phase insulin response to GIP infusion at 7mmol/l
timeFrame: 1-3 days after dexamethasone treatment
Other outcomes:
measure: Total insulin response to arginine infusion
timeFrame: 1-3 days after dexamethasone
Locations:
city: Copenhagen NV
country: Denmark
facility: Bispebjerg University Hospital
Study officials:
affiliation: Bispebjerg Hospital
name: Thure Krarup, dr. med.
role: STUDY_DIRECTOR
References:
citation: Eriksen M, Jensen DH, Tribler S, Holst JJ, Madsbad S, Krarup T. Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance. Diabetologia. 2015 May;58(5):920-8. doi: 10.1007/s00125-015-3522-y. Epub 2015 Mar 9.