The metabolic syndrome incorporating obesity, hypertension, dyslipidemia and elevated plasma glucose has reached epidemic proportions in many countries leading to an increased prevalence of type 2 diabetes (T2D) and cardiovascular disease (CVD).  Dyslipidemia, as assessed by standard measures (raised plasma triglycerides and LDL-cholesterol, and decreased HDL-cholesterol) is an independent risk factor for T2D and CVD.  However, current risk prediction algorithms have limited accuracy.   Further to this, the mechanistic links between dyslipidemia, T2D and CVD are complex and not well understood.  Lipidomics presents a new set of tools to address these issues.

We have developed a targeted lipidomics platform using liquid chromatography electrospray ionization-tandem mass spectrometry to profile 300-400 lipids from 10 mL plasma.  We have applied this technology to multiple clinical and population based cohorts to define the plasma lipid profiles associated with T2D and CVD and evaluate the potential application of these profiles to diagnose, assess disease risk and inform on disease pathogenesis. 

Regression analysis adjusting for covariates (age, sex, systolic blood pressure and obesity) identified multiple lipid species that were significantly associated with prevalent and incident T2D or CVD. Multivariate analysis incorporating unsupervised feature correlation minimization and reliefF feature selection was employed to create and test multivariate classification and risk assessment models incorporating different numbers of lipids and other risk factors.   Models incorporating lipids performed better than models based solely on traditional risk factors. 

Plasmalogens, a class of lipids with anti-oxidative and anti-inflammatory properties, were negatively associated with prevalent and incident CVD. We subsequently investigated the potential of batyl alcohol (BA, metabolic precursor to plasmalogen) to modulate plasmalogen levels and attenuate the development of atherosclerosis in ApoE^-/- and ApoE^-/-GpX1^-/- mice fed a high-fat diet. The mice without BA developed extensive atherosclerotic plaques throughout the aorta. This was reduced by 70% (P<0.001) in the BA-treated mice.

Plasma lipid profiling can provide insight into disease pathogenesis and may contribute to a new approach to risk stratification and therapeutic intervention in T2D and CVD.