• Fumiaki Imamura, Stephen J Sharp, Albert Koulman, Matthias B Schulze, Janine Kröger, Julian L Griffin, José M Huerta, Marcela Guevara, Ivonne Sluijs, Antonio Agudo, Eva Ardanaz, Beverley Balkau, Heiner Boeing, Veronique Chajes, Christina C Dahm, Courtney Dow, Guy Fagherazzi, FeskensEdith J MEJMDepartment of Agrotechnology and Food Sciences, Wageningen University, Wageningen, Netherlands., Paul W Franks, Diana Gavrila, Marc Gunter, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Tilman Kühn, Olle Melander, Elena Molina-Portillo, Peter M Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, Salvatore Panico, Olov Rolandsson, Sabina Sieri, Carlotta Sacerdote, Nadia Slimani, SpijkermanAnnemieke M WAMWNational Institute for Public Health and the Environment, Bilthoven, Netherlands., Anne Tjønneland, Rosario Tumino, Yvonne T van der Schouw, Claudia Langenberg, Elio Riboli, Nita G Forouhi, and Nick J Wareham.
• Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
• PLoS Med. 2017 Oct 1; 14 (10): e1002409e1002409.

BackgroundCombinations 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.Methods And FindingsWe 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 < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.ConclusionsA 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.

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