Abstract
BackgroundWhether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.Methods and FindingsPlasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88–0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77–0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85–0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.ConclusionsThese large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.
Highlights
Recognition of the importance of dietary fat quality rather than a focus on total fat intake has led to the promotion of dietary guidelines that encourage the consumption of polyunsaturated fatty acids (PUFAs) for cardiometabolic health [1]
In European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, among longchain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with type 2 diabetes (T2D) (HR per standard deviation [SD] 0.93; 95% confidence intervals (95% CI) 0.88–0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated
Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77–0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85–0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with hazard ratio (HR) between 1.13 to 1.46 per SD
Summary
Recognition of the importance of dietary fat quality rather than a focus on total fat intake has led to the promotion of dietary guidelines that encourage the consumption of polyunsaturated fatty acids (PUFAs) for cardiometabolic health [1]. Dietary n-3 (omega-3) PUFAs, including alpha-linolenic acid (ALA, 18:3n-3) from plant sources and eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and docosapentaenoic acid (DPA, 22:5n-3) from fish or seafood sources, are postulated to be beneficial for the prevention of type 2 diabetes (T2D), but there is inconclusive evidence from both intervention and observational studies. There has been an ongoing debate about whether dietary linoleic acid (LA; 18:2n6), the most abundant n-6 PUFA, has adverse health effects and whether its consumption should be limited in the population [14,15,16]. Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Measured plasma PUFAs can help to clarify these associations
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