Plasma Lipidomic Profiling and Risk of Type 2 Diabetes in the PREDIMED Trial

Identifier:  imarina:4098950

Handle: https://hdl.handle.net/20.500.11797/imarina4098950

Authors:  Razquin, Cristina; Toledo, Estefania; Clish, Clary B; Ruiz-Canela, Miguel; Dennis, Courtney; Corella, Dolores; Papandreou, Christopher; Ros, Emilio; Estruch, Ramon; Guasch-Ferre, Marta; Gomez-Gracia, Enrique; Fito, Montserrat; Yu, Edward; Lapetra, Jose; Wang, Dong; Romaguera, Dora; Liang, Liming; Alonso-Gomez, Angel; Deik, Amy; Bullo, Monica; Serra-Majem, Lluis; Salas-Salvado, Jordi; Hu, Frank B; Martinez-Gonzalez, Miguel A

Abstract:
© 2018 by the American Diabetes Association. 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.