Type 2 Diabetes
Conditions
Keywords
diabetes, glitazones, HDL
Brief summary
HDL from patients with type 2 diabetes show a significant reduction of their endothelium-dependent vasodilatory effect. The primary objective of the study is to analyze whether treatment with glitazones (pioglitazone and rosiglitazone)may improve the endothelium-dependent vasodilatory effect of HDL lipoproteins in patients with type 2 diabetes. The secondary objectives are: * to analyze the effect of glitazone treatment on phospholipase A2 * to look for possible differences between the effects of pioglitazone and those of rosiglitazone * to analyze the glycemic response to glitazone therapy according to clinical and biological baseline characteristics.
Detailed description
The study will be performed as follows: At baseline, before initiating glitazone treatment, clinical data will be recorded and blood samples will be obtained for biological measurements (blood glucose, HbA1c, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, liver enzymes), phospholipase A2 measurement and the study of the vasodilatory effect of HDL particles.For this purpose, we will study,using rabbit aorta rings,the ability of HDL to suppress the inhibition of vasodilation that is induced by oxidised LDL. For all the patients included into the study, a treatment by pioglitazone (at an initial dose of 30 mg/day) or rosiglitazone (at an initial dose of 4 mg/day) will be given by randomization. A visit will be performed at week 12, in order to titrate the glitazone dose (up to 45 mg/day for pioglitazone, up to 8 mg/day for rosiglitazone)according to HbA1c level and values of self-monitoring blood glucose. At week 24, the last visit will take place. During this visit, clinical data will be recorded and blood samples will be obtained for biological measurements (blood glucose, HbA1c, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, liver enzymes), phospholipase A2 measurement and the study of the vasodilatory effect of HDL particles.
Interventions
DRUGpioglitazone
After randomization, patients will be treated by pioglitazone or rosiglitazone
DRUGrosiglitazone
treatment with rosiglitazone at a dose between 4mg and 8 mg/day
Sponsors
Centre Hospitalier Universitaire Dijon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients with type 2 diabetes treated by oral antidiabetic agents (except glitazones) and/or insulin * age\> 18 years * HbA1c \> 6.5%
Exclusion criteria
* renal failure * heart failure * primary hyperlipidemia * pregnancy * treatment that may modify lipid metabolism (glucocorticoids, oestrogens, retinoids, HIV antiviral drugs)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Action of glitazone on the endothelium-dependent vasodilatory effects of HDL lipoproteins | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Look for possible differences between pioglitazone and rosiglitazone for their effects on HDL lipoproteins and phospholipase A2 | 6 months |
| Effect of glitazone therapy on Phospholipase A2 level | 6 months |
| Analyze the glycemic response to glitazones according to baseline clinical and biological characteristics | 6 months |
Countries
France
Outcome results
None listed