Incretin Physiology Associated With Steroid Hormone Treatment

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Type 2 Diabetes Mellitus, Steroids

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>10 healthy Caucasian subjects without family history of diabetes | Other: Oral glucose test (OGTT); isoglycaemic iv. clamp; liquid meal test; Gastric Emptying Rate; Prednisolone; Paracetamol<br>* 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<br>* Other names: Paracetamol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GLP-1 and GIP response curves |  | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incretin Effect, Steroids, Glucagon-Like Peptide 1, Gastric Inhibitory Peptide, Glucose-dependent Insulinotropic Polypeptide, Insulin, C-peptide, Glucagon