Abstract 568: Lipidomic Comparison of Hyperglycemic and Normal Subjects Using Absolute Quantitation of >700 Lipid Species

Abstract

The presence of diabetes mellitus in patients significantly increases the risk of cardiovascular disease, among many negative health outcomes. Several research groups have reported lipid species anomalies in subjects showing insulin resistance, including higher concentrations of sphingomyelin species relative to normal controls. Advances in lipidomic methodologies has allowed for the profiling of numerous lipid species in a single extraction and analytical run. We used the SCIEX Lipidyzer platform to determine the absolute concentration of 770 distinct lipid species from 52 subjects categorized into hyperglycemic (n=30) and normal subjects (n=22). Lipid species were determined from the following classes: cholesterol esters (CE), ceramides (CER), diacylglycerols (DAG), dihydroceramide (DCER), free fatty acids (FFA), hexosylceramides (HCER), lactosylceramides (LCER), lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE), phosphatidylcholines (PC), phosphatidylethanolamines (LPE), sphingomyelins (SM), and triacylglycerols (TAG). After normalizing by the sum of total apolipoprotein A and apolipoprotein B (to account for the possibility of reduced particle number due to medicinal intervention), lipids both by class and species were compared using one way analysis of variance. On a class level, relative to normal subjects, hyperglycemic patients showed increased levels of CER and FFA. Individual lipid species of these classes that were higher in hyperglycemic patients include CER(18:0), CER(20:0), CER(24:1), FFA(16:0), FFA(16:1), FFA(18:0), FFA(18:1), FFA(18:2), FFA(18:3), and FFA(20:3) Differences were also found in SM concentrations between hyperglycemic and normal patients resulting in a higher the SM/PC ratio, indicating changes in the lipid fluidity of the shell in lipoprotein particles of hyperglycemic patients. On a species level, SM(16:0), SM(18:1), and SM(24.1), were elevated in hyperglycemic subjects relative to normal subjects. This finding of elevated unsaturated SM species in hyperglycemic patients is at odds with other studies where it was found that the saturated SM moieties were elevated in insulin resistant subjects.