Clinical trial NCT00713440: Incretin Physiology Associated With Steroid Hormone Treatment
Official title: Incretin Physiology and Beta-Cell Function Before and After Treatment With Steroid Hormone in Healthy Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Steroids
Keywords: Incretin Effect
Steroids
Glucagon-Like Peptide 1
Gastric Inhibitory Peptide
Glucose-dependent Insulinotropic Polypeptide
Insulin
C-peptide
Glucagon
Lead sponsor: Glostrup University Hospital, Copenhagen
Sponsor class: OTHER
First posted: 2008-07-11
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this study is to evaluate whether the reduced incretin effect and the paradoxical glucagon responses during oral glucose ingestion and isoglycaemic iv glucose infusion observed in patients with type 2 diabetes are causes (non-inducible in lean healthy subjects without family history of diabetes) or consequences (inducible) of the diabetic state.

Detailed description: The incretin effect is severely reduced in patients with type 2 diabetes. This pathophysiological trait is accompanied by an almost abolished insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) and a reduced insulinotropic potency of the other incretin hormone glucagon-like peptide-1 (GLP-1). Furthermore, recent studies suggest that hypersecretion of glucagon during oral glucose ingestion, as opposed to a normal suppression of glucagon during isoglycaemic intravenous (iv) administered glucose, further attenuates the incretin effect in patients with type 2 diabetes.

However, it remains unclear whether the severely reduced incretin effect and its accompanying pathophysiological traits characterizing patients with type 2 diabetes can be induced temporarily in healthy subjects by a short period of glucose homeostatic dysregulation.

In this study the incretin effect will be measured using 50-g oral glucose tolerance test and isoglycaemic iv glucose infusion and meal test in 10 healthy Caucasian subjects without family history of diabetes before and after dysregulation of glucose homeostasis using high calorie diet, physical inactivity and administration of adrenocortical steroids

Eligibility criteria: Inclusion Criteria:

* Caucasians without Type 2 or Type 1 Diabetes
* Normal OGTT (75 g of glucose) according to WHO criteria
* Normal hemoglobin
* Normal blood pressure

Exclusion Criteria:

* Liver disease
* Kidney disease
* Relatives (parents/siblings) with type 2 diabetes
* Pregnancy
* Contra-indications to treatment with adrenocortical steroids

Primary outcomes:
measure: Incretin effect before and after dysregulation of glucose homeostasis using high calorie diet, physical inactivity and administration of adrenocortical steroids.
timeFrame: One year
Secondary outcomes:
measure: GLP-1 and GIP response curves
timeFrame: One year
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Clinical Physiology Department; Glostrup Univesity Hospital
state: Region Hovedstaden
Study officials:
affiliation: Gentofte University Hospital
name: Filip K Knop, MD; Ph-D
role: STUDY_DIRECTOR
affiliation: University of Copenhagen
name: Tina Vilsboll, MD; Ph-D, DMSc
role: STUDY_CHAIR
affiliation: Glostrup University Hospital
name: Katrine B Hansen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Glostrup University Hospital
name: Steen Larsen, MD; DMSc
role: STUDY_CHAIR
affiliation: University of Copenhagen
name: Jens J Holst, Professor: DMSc
role: STUDY_CHAIR
References:
citation: Hansen KB, Vilsboll T, Bagger JI, Holst JJ, Knop FK. Increased postprandial GIP and glucagon responses, but unaltered GLP-1 response after intervention with steroid hormone, relative physical inactivity, and high-calorie diet in healthy subjects. J Clin Endocrinol Metab. 2011 Feb;96(2):447-53. doi: 10.1210/jc.2010-1605. Epub 2010 Nov 3.