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, type 2 diabetes cases=536; median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentration in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-gamma-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). Delta-5 desaturase (D5D) activity was estimated as 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. SNPs in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes.

Conclusion: Plasma n-6 PUFA were associated differently with type 2 diabetes depending on fatty acid and the lipid class.