The peripheral effects of prednisolone on glucose metabolism, metabolic hormones, insulin sensitivity and insulin secretion in healthy young males and males with metabolic syndrome * two randomized, placebo controlled, double blind, dose-response, parallel group intervention studies.

Completed

Conditions: Metabole effecten van behandeling met prednisolon
metabolic effects of prednisolone
glucocorticoid-induced insulin resistance
10018424
10062915

Registration Number: NL-OMON31204

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 124

Inclusion Criteria

For all participants:
1. signed informed consent
2. caucasian male
3. normal day-and night rythm
For healthy volunteers:
1. Good health (from history, physical exams, blood tests)
2. fasting glucose < 5.6 mmol/L
3. 20 < BMI< 25.
4. 20 < age < 55 jaar.
For subjects with the metabolic syndrome:
1. metabolic syndrome (according to IDF criteria). Waist > 93 cm and at least 3 of the following criteria:
- triglycerides > 1.7 mmol/L
- HDL cholesterol < 1.03 mmol/L
- blood pressure > 130/85 mmHg
- disturbed glucose tolerance (definded as: fasting glucose between 5.6 en 6.1 mmol/L en 2 hr plasma glucose after oral glucose tolerance test < 11.0 mmol/L).

Exclusion Criteria

For all participants:
1. allergy for prednisolone
2. any other contra-indication for prednisolone use.
3. use of glucocorticoids in the past 3 months
4. Recent participation in a clinical trial
5. Blood donation in the past 3 months
6. (history of) alcohol or drugs abuse.
7. Not willing or able to sign the informed consent or not being able to understand the study information
8. smoking
for healthy males:
1. any present disorder
2. any medication use, except for incidental use of analgesic agents
3. 1ste degree relative with type 2 diabetes
4. intensive physical activity (sport) > 2x/week.
For males with the metabolic syndrome:
1. serious (pulmonary, liver, kidney) diseases
2. history of cardiovascular disease (such as MI or CVA)
3. psychiatric disorder
4. depression
5. any condition that interferes with the HPA axis
6. malignancy
7. other condition or usage of medication that may interfere with study endpoints of hypothesis. Eligibility will be assessed in each individual case by the research physician and internist.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>In PANTHEON-I, various aspects of beta-cell function will be studied after<br /><br>intravenous (combined eu- and hyperglycemic clamp with subsequent arginine<br /><br>stimulation) and orally (mixed-meal test) administered glucose.<br /><br><br /><br>In PANTHEON-II, GC-induced changes in hepatic and peripheral insulin<br /><br>sensitivity and subsequent changes in intermediary metabolism/metabolic fluxes,<br /><br>such as rate of endogenous glucose production, lipolysis and proteolysis, and<br /><br>the underlying molecular mechanism, will be studied. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secundary outcomes of PANTHEON-I:<br /><br>1. circulating biomarkers (plasma)<br /><br>2. Microvascular function<br /><br>3. Blood pressure<br /><br>4. Molecular mechanisms<br /><br><br /><br>Secundaire uitkomsten van PANTHEON-II betreffen de effecten van bovengenoemde<br /><br>interventie met prednisolon op:<br /><br>1. circulating biomarkers (plasma)<br /><br>2. Body composition<br /><br>3. Blood pressure<br /><br>4. body fat distribution<br /><br>5. Molecular mechanisms </p><br>