Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study

OBJECTIVE Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class–specific PUFA concentrations with type 2 diabetes risk. RESEARCH DESIGN AND METHODS In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study: subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The Δ-5 desaturase (D5D) activity was estimated as the 20:4/20:3 ratio. Associations with diabetes were estimated with Cox proportional hazards models. RESULTS Higher concentrations of 18:2 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio [HR] per 1 SD 0.53; 95% CI 0.23–1.26) and monoacylglycerols (HR 0.59; 0.38–0.92). Higher concentrations of 20:3 in phospholipid classes phosphatidylcholines (HR 1.63; 1.23–2.14), phosphatidylethanolamines (HR 1.87; 1.32–2.65), and phosphatidylinositol (HR 1.40; 1.05–1.87); free fatty acids (HR 1.44; 1.10–1.90); and cholesteryl esters (HR 1.47; 1.09–1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 20:4 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. CONCLUSIONS Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.