The effects of dietary fat and genotype on insulin sensitivity : the LIPGENE Dietary Intervention Study

Abstract

The Metabolic Syndrome (MetS) is characterised by hyperinsulinaemia, low glucose tolerance, dyslipidaemia (increased triacylglycerol, (TAG) and non-esterified fatty acids (NEFA) and reduced high density lipoprotein (HDL)-cholesterol concentrations), hypertension and obesity. This cluster of factors has been recognised for many years and was formally labelled in 1988 by Gerald Reaven who suggested that insulin resistance is the key metabolic perturbation. Given recent evidence that dietary interventions have been more effective than pharmacological agents in preventing the development of the MetS and T2DM in high-risk individuals, exploration of the concept that altered dietary fat intake may attenuate the impact of the MetS warrants investigation. The objective of this thesis was to examine the relationship between dietary and plasma fatty acids and insulin sensitivity at baseline and after a 12-week dietary intervention in subjects with the MetS. It also served to determine if the IRS-1 genetic polymorphism Gly972R associated with increased risk of the MetS played a causal role in determining an individual’s responsiveness to dietary fat modification.