Plasma lipidomic profiling and risk of type 2 diabetes in the PREDIMED trial. Academic Article uri icon


  • OBJECTIVE:Specific 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. RESEARCH DESIGN AND METHODS: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. RESULTS: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 <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs. CONCLUSIONS: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.


  • Razquin, Cristina
  • Toledo, Estefanía
  • Clish, Clary B
  • Ruiz-Canela, Miguel
  • Dennis, Courtney
  • Corella, Dolores
  • Papandreou, Christopher
  • Ros, Emilio
  • Estruch, Ramon
  • Guasch-Ferré, Marta
  • Gómez-Gracia, Enrique
  • Fitó, Montserrat
  • Yu, Edward
  • Lapetra, José
  • Wang, Dong
  • Romaguera, Dora
  • Liang, Liming
  • Alonso-Gómez, Angel
  • Deik, Amy
  • Bullo, Mónica
  • Serra-Majem, Lluis
  • Salas-Salvadó, Jordi
  • Hu, Frank B
  • Martinez-Gonzalez, Miguel A

publication date

  • 2018