Clinically relevant variability of the lipidome in people with type 2 diabetes

Background Besides hyperglycemia, type 2 diabetes (T2D) is characterized by dyslipidemia, which is typically assessed using traditional clinical lipid measurements. However, molecular plasma lipids beyond these traditional markers can provide additional information about an individuals health status. For molecular lipids to be used effectively, certain characteristics, such as their temporal variability, need to be determined. Methods We analyzed the plasma lipidome for three consecutive time points, each three months apart, of 51 individuals with T2D using targeted liquid chromatography coupled to mass spectrometry (LC-MS). 513 lipid species across 25 (sub)classes were quantified by this approach and the temporal variability were calculated. Moreover, to identify sex differences in the plasma lipidome, we analyzed 914 samples of a cross-sectional T2D cohort with the same approach. Results Neutral lipids and phosphatidylserine had the highest temporal variability which was independent of their platform-specific variability. In contrast, glycosphingolipids were found to be relatively stable over time in individuals with T2D. Acyl-chain analysis revealed generally similar variability in the acyl-chain groups but indicated a higher temporal variability in medium-length acyl-chains. Lipid-sex association analysis showed markedly higher sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines in women and higher acylcarnitines in men. Overall, approximately one-third of measured lipids showed significant sex differences independent of age, BMI, diabetes duration, glycemic control, and medication use. Conclusions Our findings provide insights into temporal variability of molecular lipids. This variability should be considered when assessing novel lipid biomarkers. Likewise, sex differences in these lipids need to be considered in precision medicine for diabetes management.