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van CCT (UK)

van CCT (UK)

The role of free fatty acids in the glucose-lowering effects of thiazolidinediones.

- candidate number1898
- NTR NumberNTR551
- Date ISRCTN created14-feb-2006
- date ISRCTN requested13-jan-2006
- Date Registered NTR18-dec-2005
- Secondary IDsN/A 
- Public TitleThe role of free fatty acids in the glucose-lowering effects of thiazolidinediones.
- Scientific TitleThe role of free fatty acids in the glucose-lowering effects of thiazolidinediones.
- hypothesisThiazolidinediones (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.
- Healt Condition(s) or Problem(s) studiedDiabetes Mellitus Type 2 (DM type II)
- Inclusion criteria1. 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 criteria1. 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.
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingSingle
- controlPlacebo
- groupParallel
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-sep-2002
- planned closingdate31-mei-2005
- Target number of participants13
- Interventions1. 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.
- Primary outcomeBasal glucose production and plasma FFA peripheral insulin sensitivity insulin-mediated suppression of FFA (=insulin sensitivity of adipose tissue).
- Secondary outcomeChanges in concentrations of ceramide and glycosphingolipids in skeletal muscle.
- TimepointsN/A
- Trial web siteN/A
- statusstopped: trial finished
- Sponsor/Initiator Academic Medical Center (AMC), Department of Endocrinology and Metabolism
- Funding
(Source(s) of Monetary or Material Support)
Eli Lilly Nederland B.V., Fellowship award from the European Society of Parenteral and Enteral Nutrition
- PublicationsJ Clin Endocrinol Metab. 2007 Jan;92(1):166-71. Epub 2006 Oct 24.
- Brief summaryThe 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 TZDís on IR induced by a high fat diet or acutely elevation of plasma FFA, but this protecting effect by TZDís 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 TZDís 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.
- Main changes (audit trail)
- RECORD18-dec-2005 - 14-aug-2008

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