Imamura, FumiakiSharp, Stephen JKoulman, AlbertSchulze, Matthias BKröger, JanineGriffin, Julian LHuerta, José MGuevara, MarcelaSluijs, IvonneAgudo, AntonioArdanaz, EvaBalkau, BeverleyBoeing, HeinerChajes, VeroniqueDahm, Christina CDow, CourtneyFagherazzi, GuyFeskens, Edith J MFranks, Paul WGavrila, DianaGunter, MarcKaaks, RudolfKey, Timothy JKhaw, Kay-TeeKühn, TilmanMelander, OlleMolina-Portillo, ElenaNilsson, Peter MOlsen, AnjaOvervad, KimPalli, DomenicoPanico, SalvatoreRolandsson, OlovSieri, SabinaSacerdote, CarlottaSlimani, NadiaSpijkerman, Annemieke M WTjønneland, AnneTumino, Rosariovan der Schouw, Yvonne TLangenberg, ClaudiaRiboli, ElioForouhi, Nita GWareham, Nick J2023-01-252023-01-252017-10-11http://hdl.handle.net/10668/11666Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/BiomarkersCase-Control StudiesCohort StudiesCross-Sectional StudiesDiabetes Mellitus, Type 2EuropeFatty AcidsFemaleHumansIncidenceInternationalityMaleMiddle AgedPhospholipidsPrincipal Component AnalysisProspective StudiesRandom Allocationresearch article29020051open access10.1371/journal.pmed.10024091549-1676PMC5636062https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002409&type=printablehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636062/pdf