Impaired Glucose Tolerance, Metabolic Syndrome
Conditions
Keywords
11ß-hydroxysteroid dehydrogenase, rosiglitazone, insulin sensitivity, Impaired glucose tolerance
Brief summary
The purpose of this study is to determine whether the insulin sensitizing effects of rosiglitazone were accompanied by changes in 11ß-HSD1 expression and activity in different tissues. Furthermore the metabolic and hormonal effects of PPAR gamma stimulation by rosiglitazone will be analysed in several tissues.
Detailed description
The PPARgamma agonist rosiglitazone (R) increases insulin sensitivity, which is comparable to the effects of a reduction in 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in animal models. We therefore aimed to investigate whether rosiglitazone-induced insulin sensitivity is associated with changes in 11β-HSD1 activity in different tissues in subjects suffering from impaired glucose tolerance. Furthermore the metabolic and hormonal effects of PPAR gamma stimulation by rosiglitazone will be analysed in those tissue samples.
Interventions
DRUGrosiglitazone
89 mg BID for 8 weeks, orally
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Impaired glucose tolerance
Exclusion criteria
* Treatment with insulin * Orally taken antidiabetic medication, glucocorticoids or vitamin K-antagonists * Heart failure * Impaired hepatic or renal function * Anaemia * Disturbed coagulation * Any other endocrine disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| changes of 11ß-HSD1 expression in adipose tissue and skeletal muscle during 8 weeks of rosiglitazone treatment | 8 weeks | 11ß-HSD1 expression will be measured in adipose tissue and skeletal muscle |
| changes of hepatic 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment | 8 weeks | 11ß-HSD1 activity will be assessed by measuring conversion of cortisone to cortisol (ratio will be calculated) |
| changes of whole body 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment | 8 weeks | whole body 11ß-HSD1 activity will be assessed by measuring the ratio of urinary tetrahydrocortisol (THF) + alpha-tetrahydrocortisol (THF) / tetrahydrocortisone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in insulin sensitivity during 8 weeks of rosiglitazone treatment | 8 weeks | Measurement of whole body and myocellular insulin sensitivity (mg•kg-1•min-1/(mU•L-1)) before and after treatment |
| Hormonal and metabolic changes induced by the intervention | 3 months | Whole body as well as tissue specific (skeletal muscle and different adipose tissue compartment) changes in hormonal circuits and metabolism will be analyzed |
| changes of FGF-21 induced by the intervention | 8 weeks | FGF-21 (ng/ml) will be assessed in plasma samples |
| changes of free fatty acids (FFA) induced by the intervention | 8 weeks | FFA (mmol/l) will be assessed in plasma samples |
| changes of myocellular SCD1 expression induced by the intervention | 8 weeks | myocellular SCD1 mRNA expression will be assessed |
| changes of myocellular long chain fatty acids (LC-FA) expression induced by the intervention | 8 weeks | myocellular LC-FA mRNA expression will be assessed |
Countries
Germany
Outcome results
None listed