Suvitaival T, et al. - The physicians embraced this study to examine whether the plasma molecular lipidome had biomarker potential to predict the onset of type 2 diabetes mellitus (T2DM). They demonstrated that a lipid signature characteristic of T2DM was present years before the diagnosis and improved prediction of progression to T2DM. Also, in a high-risk group, molecular lipid biomarkers were shown to have predictive power, where standard risk factors were not helpful at distinguishing progressors from non-progressors.

• Global lipidomic profiling was applied on plasma samples from well-phenotyped men (107 cases, 216 controls) participating in the longitudinal METSIM study at baseline and at five-year follow-up.
• Besides, an additional study with a representative sample of adult male population (n = 631) was performed to validate the lipid markers.
• Using the lipidomics platform based on ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry, 277 plasma lipids were analyzed.
• For the development of T2DM, lipids with the highest predictive power were computationally selected, validated and compared to standard risk models without lipids.

• The physicians observed a persistent lipid signature with higher levels of triacylglycerols and diacyl-phospholipids as well as lower levels of alkylacyl phosphatidylcholines in progressors to T2DM.
• They selected lysophosphatidylcholine acyl C18:2 (LysoPC(18:2)), phosphatidylcholines PC(32:1), PC(34:2e) and PC(36:1), and triacylglycerol TG(17:1/18:1/18:2) to the full model that included metabolic risk factors and FINDRISC variables.
• For progression to T2DM, these lipids had respective odds ratios of 0.32, 2.4, 0.50, 2.2 and 0.31 (all p < 0.05), when further adjusting for BMI and age.
• In this study, the independently-validated predictive power improved in all pairwise comparisons among the lipid model and the respective standard risk model without the lipids (integrated discrimination improvement IDI > 0; p < 0.05).
• Prominently, in the fasting plasma glucose-matched subset of the validation study, the lipid models remained predictive of the development of T2DM.