No registrations found.
ID
Source
Brief title
Health condition
Patients with DM II.
Sponsors and support
Intervention
Outcome measures
Primary outcome
Basal glucose production and plasma FFA
peripheral insulin sensitivity
insulin-mediated suppression of FFA (=insulin sensitivity of adipose tissue).
Secondary outcome
Changes in concentrations of ceramide and glycosphingolipids in skeletal muscle.
Background summary
The prevalence of Diabetes Mellitus Type II (DM II) is increasing in
line with the prevalence of obesity. Insulin resistance (IR) is a key
feature of DM II. The pathophysiological mechanism of IR is probably
multifactorial with an important role for free fatty acids (FFA).
Thiazolidinediones (TZD) increase peripheral insulin sensitivity via a
partially elucidated mechanism, one of them probably via lowering of
plasma FFA.
Several animal studies showed a protective effect of TZD’s on IR
induced by a high fat diet or acutely elevation of plasma FFA, but
this protecting effect by TZD’s was not seen in obese normal glucose
tolerant humans during infusion of lipid.
We conducted a single blinded placebo-controlled randomized study to
evaluate the protecting effect of TZD’s on FFA induced IR in obese
patients with DM II after treatment for 4 months with Pioglitazone.
We
hypothesized that treatment with Pioglitazone would not protect obese
patients with DM II from FFA-induced insulin resistance.
Study objective
Thiazolidinediones (TZD's, Pioglitazone) lower free fatty acids (FFA) in plasma via increased insulin sensitivity (=decreased lipolysis) in adipose tissue. The decrease in plasma FFA results in increased insulin sensitivity in skeletal muscle. Increasing plasma FFA to baseline levels while on TZD-treatment, will decrease peripheral insulin senstivity to pre-treatment levels indicating that the mechanism of action of Pioglitazone is not directly on muscle but via lowering of plasma FFA due to the beneficial effects on adipose tissue.
Study design
N/A
Intervention
1. Treatment with pioglitazone 30 mg once a day or placebo;
2. Infusion of a lipid emulsion on the third study day in the active treatment group.
P.O. Box 22660
M.J.M. Serlie
Meibergdreef 9
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5669111
m.j.serlie@amc.uva.nl
P.O. Box 22660
M.J.M. Serlie
Meibergdreef 9
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5669111
m.j.serlie@amc.uva.nl
Inclusion criteria
1. Obese patients with Diabetes Mellitus type II (DM II);
2. BMI > 25 kg/m2;
3. Treatment for DM II with oral medication only;
4. Moderatly regulated DM II.
Exclusion criteria
1. Use of insulin;
2. Use of fibrates;
3. Plasma creatinine > 150 umol/L;
4. Transaminases > 2x upper limit of reference value;
5. Impaired cardiac function or angina pectoris;
6. Familial lipid metabolism disorder;
7. Women in reproductive age;
8. Epilepsy;
9. Proliferative retinopathy.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL509 |
| NTR-old | NTR551 |
| Other | : N/A |
| ISRCTN | ISRCTN47118569 |