Steroids, Type 2 Diabetes Mellitus
Conditions
Keywords
Incretin Effect, Steroids, Glucagon-Like Peptide 1, Gastric Inhibitory Peptide, Glucose-dependent Insulinotropic Polypeptide, Insulin, C-peptide, Glucagon
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
Interventions
OTHEROral glucose test (OGTT); isoglycaemic iv. clamp; liquid meal test; Gastric Emptying Rate; Prednisolone; Paracetamol
OGTT: The test is performed with 50 g of glucose deluded in 300 ml. of water. Isoglycaemic iv. clamp: Iv glucose infusion mimicking the glucose response curve of the OGTT. Liquid Meal Test: The test is performed with 100g of formula milk in 300 ml. of water. Gastric Emptying Rate: Paracetamol absorption test. Adrenocortical Steroids: Use of 37,5 mg./day of prednisolone during 10 days
Sponsors
Glostrup University Hospital, Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incretin effect before and after dysregulation of glucose homeostasis using high calorie diet, physical inactivity and administration of adrenocortical steroids. | One year |
Secondary
| Measure | Time frame |
|---|---|
| GLP-1 and GIP response curves | One year |
Countries
Denmark
Outcome results
None listed