The effect of pioglitazone and fish oils on the regulation of fat transport in subjects with the metabolic syndrome

INTERVENTION: 4 parellel groups. Pioglitazone and Fish oils (Omacor) alone will be compared with a no treatment group and a combined Pioglitazone and Fish oils (Omacor) group. Group 1. Pioglitazone alone 45mg oral tablets daily for a total of 12 weeks Group 2. Fish oils (Omacor) alone 4 1000mg oral capsules daily for a total of 12 weeks Group 3. Combined Pioglitazone 45mg oral tablets daily and Fish oils (Omacor) 4 1000mg oral capsules daily for a total of 12 weeks Group 4. No treatment group CONDITION: Metabolic syndrome PRIMARY OUTCOME: To examine the independent and combined effects of Pioglitazone and Fish Oils (Omacor) on Very Low Density Lipoprotein (VLDL) transport in metabolic syndrome subjects. VLDL transport will be used as an assessment tool of triglyceride transport. VLDL transport will be determined and compared between groups. All analysis will be carreid out using Statistical Package for the Social Sciences(SPSS). Differences between the four groups prior to randomization will be determined by one‐way Analysis of Variance(ANOVA), after logarithmic transformation of skewed variables. Main and interactive treatment effects will be examined using general linear modelling adjusted for baseline covariates. Associations between kinetic estimates of lipid and lipoprotein, liver fat and other metabolic variables will be examined using simple and multiple linear regression methods. Compartmental analysis will be used to develop and fit models to lipid and lipoprotein tracer data. To examine the independent and combined effects of Pioglitazone and Fish Oils (Omacor) on VLDL‐apolipoprotein B (apoB) production in metabolic syndrome subjects. VLDL‐apoB production will be used as an assessment tool of apoB transport. VLDL‐apoB production will be determined and compared between groups. All analysis will be carreid out using SPSS. Differences between the four groups prior to randomization will be determined by one‐way ANOVA, after logarithmic transformation of skewed variables. Main and interactive treatment effects will be examined using general linear modelling adjusted for baseline covariates. Associations between kinetic estimates of lipid and lipoprotein, liver fat and other metabolic variables will be examined using simple and multiple linear regression methods. Compartmental analysis will be used to develop and fit models to lipid and lipoprotein tracer data. INCLUSION CRITERIA: Non‐smoking men aged 18‐75 years and post menopausal women aged =75 years will be recruited. In this study we will define the metabolic syndrome on a composite of published criteria: waist circumference >94cm for men and >80cm for women, triglycerides >1.7mmol/L and/or High Density Lipoprotein (HDL)‐cholesterol <1.0mmol/L, and Homeostais assessment (HOMA) score >2.5 (>75th percentile of a reference range). To define hepatic steatosis, we will select only metatbolic syndrome subjects with Alanine transaminase (ALT) levels >20U/L. SECONDARY OUTCOME: To examine the independent and combined effects of Pioglitazone and Fish Oils (Omacor) on liver fat in metabolic syndrome subjects. Liver fat content will be used as an assessment tool of fat storage in the liver. Liver fat will be determined and compared between groups. All analysis will be carreid out using SPSS. Differences between the four groups prior to randomization will be determined by one‐way ANOVA, after logarithmic transformation of skewed variables. Main and interactive treatment effects will be examined using general linear modelling adjusted for baseline covariates. Associations between kinetic estimates of lipid and lipoprotein, liver fat and other metabolic variables will be examined using simple and multiple linear regression methods. Compartmental analysis will be used to develop and fit models to lipid and lipoprotein tracer data.