Incretin Physiology Associated With Steroid Hormone Treatment

Condition(s) targeted: Type 2 Diabetes Mellitus; Steroids

Intervention: Oral glucose test (OGTT); isoglycaemic iv. clamp; liquid meal test; Gastric Emptying Rate; Prednisolone; Paracetamol (Other)

Phase: N/A

Status: Recruiting

Sponsored by: Glostrup University Hospital,Copenhagen

Official(s) and/or principal investigator(s):
Filip K Knop, MD; Ph-D, Study Director, Affiliation: Gentofte University Hospital
Tina Vilsboll, MD; Ph-D, DMSc, Study Chair, Affiliation: Herlev University Hospital
Katrine B Hansen, MD, Principal Investigator, Affiliation: Glostrup University Hospital
Steen Larsen, MD; DMSc, Study Chair, Affiliation: Glostrup University Hospital
Jens J Holst, Professor: DMSc, Study Chair, Affiliation: University of Copenhagen

Overall contact:
Katrine B Hansen, MD, Phone: +45 40509942, Email: kabaha01@glo.regionh.dk

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.

Official title: Incretin Physiology and Beta-Cell Function Before and After Treatment With Steroid Hormone in Healthy Individuals

Study design: Other, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study

Primary outcome: Incretin effect before and after dysregulation of glucose homeostasis using high calorie diet, physical inactivity and administration of adrenocortical steroids.

Secondary outcome: GLP-1 and GIP response curves

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

Minimum age: 18 Years. Maximum age: 40 Years. Gender(s): Both.

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

Katrine B Hansen, MD, Phone: +45 40509942, Email: kabaha01@glo.regionh.dk

Clinical Physiology Department; Glostrup Univesity Hospital, Glostrup, Region Hovedstaden 2600, Denmark; Recruiting
Katrine B Hansen, MD, Phone: +45 405099042, Email: kabaha01@glo.regionh.dk

Starting date: July 2008
Ending date: July 2009
Last updated: July 9, 2008