Abstract
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.
Highlights
Fatty acids play vital roles in metabolic homeostasis, serving as precursors of signalling molecules, energy sources, and constituents of membranes and functional lipids [1,2]
We found that incidence of type 2 diabetes was lower by 63% on average when comparing the 20% of adults with fatty acid profiles most consistent with this particular combination with the 20% of adults with fatty acid profiles least like this particular combination
We further examined the association of this combination of fatty acids with metabolic risk factors, genetic predisposition to obesity and insulin resistance, and dietary intakes in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct
Summary
Fatty acids play vital roles in metabolic homeostasis, serving as precursors of signalling molecules, energy sources, and constituents of membranes and functional lipids [1,2] Reflecting their diverse roles, fatty acids have been evaluated as markers of physiological homeostasis, metabolic disorders, and dietary exposure in biological, clinical, and population-based research [3,4,5]. Interventions of lipid-lowering drugs or dietary carbohydrates or fats, for example, alter blood concentrations of individual PUFAs and saturated fatty acids (SFAs) jointly [3,9,10,11]. These findings support the notion that combinations of fatty acids are important to study in relation to the aetiology of T2D and to predict T2D risk. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated
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