A combination of plasma phospholipid fatty acids and incidence of type 2 diabetes

Background: Combinations 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 findings: 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) to 2007 in eight European countries in EPIC-InterAct, a nested case-cohort study. Deriving the first principal component from 27 individual fatty acids (mol%) as the main exposure (subsequently described as the FA-pattern score), the FA-pattern score explained 16.1% of the overall variability of the 27 fatty acids, 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. 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 fifths of the score, the hazard ratio of incident T2D was 0.23 (95% confidence interval: 0.19-0.29) adjusted for potential confounders and 0.37 (0.27-0.50), further adjusted for cardiometabolic 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 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. Conclusions: 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.