血浆n-6多不饱和脂肪酸（PUFA）和2型糖尿病风险的证据不一致。我们检查了脂质类特定PUFA浓度与2型糖尿病风险的关联。在前瞻性欧洲癌症和营养调查（EPIC）-波茨坦队列（嵌套病例-队列研究：亚队列1084名参与者，536名2型糖尿病患者，中位随访6.5年），我们测量了12种脂质（亚）类中的血浆18:2、20:3和20:4浓度，可能反映了亚油酸（18：2n-6）、二十二碳六烯酸（20：3n-6）和花生四烯酸（20：4n-6）的血浆浓度。 Δ-5脱饱和酶（D5D）活性估计为20：4 / 20：3比率。使用Cox比例风险模型估计了与糖尿病的相关性。 18：2的浓度较高与2型糖尿病的风险呈负相关，尤其是在去甲磷酸酰胆碱（每1个标准偏差的风险比[HR]为0.53；95％CI 0.23-1.26）和单酰基甘油（HR 0.59; 0.38-0.92）中。磷脂酰胆碱中20：3的浓度较高与糖脂糖尿病的发病率有关，特别是磷脂酰胆碱（HR 1.63; 1.23-2.14），磷脂酰乙醇胺（HR 1.87; 1.32-2.65）和磷脂酰肌醇（HR 1.40; 1.05-1.87）；游离脂肪酸（HR 1.44; 1.10-1.90）和胆固醇酯（HR 1.47; 1.09-1.98），这些关联在多重测试校正后仍然具有统计学显着性。 20：4的浓度较高与风险无关。磷脂和胆固醇酯中估计的D5D活性与2型糖尿病风险降低有关。在这些脂质类中，D5D编码FADS基因中的单核苷酸多态性解释了估计的D5D活性的相对较高比例。 血浆n-6 PUFA与2型糖尿病的关联因脂肪酸和脂质类而异。

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.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.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.Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.© 2023 by the American Diabetes Association.