Razquin, CristinaToledo, EstefaníaClish, Clary BRuiz-Canela, MiguelDennis, CourtneyCorella, DoloresPapandreou, ChristopherRos, EmilioEstruch, RamonGuasch-Ferré, MartaGómez-Gracia, EnriqueFitó, MontserratYu, EdwardLapetra, JoséWang, DongRomaguera, DoraLiang, LimingAlonso-Gómez, AngelDeik, AmyBullo, MónicaSerra-Majem, LluisSalas-Salvadó, JordiHu, Frank BMartínez-González, Miguel A2023-01-252023-01-252018-10-16http://hdl.handle.net/10668/13096Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend ≤0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another profile composed of TAGs, DAGs, and PEs was associated with higher T2D risk.enAgedAged, 80 and overCardiovascular DiseasesCase-Control StudiesCohort StudiesDiabetes Mellitus, Type 2FemaleHumansIncidenceLipid MetabolismLipidsMaleMetabolomicsMiddle AgedRisk Factorsresearch article30327364open access10.2337/dc18-08401935-5548PMC6245212https://europepmc.org/articles/pmc6245212?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245212/pdf