Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
复制标题
DOI：
10.1371/journal.pmed.1002094
复制
发表时间：
2016-07
期刊：
影响因子：
15.8
通讯作者：
Wareham NJ
中科院分区：
文献类型：
--
作者：
Forouhi NG;Imamura F;Sharp SJ;Koulman A;Schulze MB;Zheng J;Ye Z;Sluijs I;Guevara M;Huerta JM;Kröger J;Wang LY;Summerhill K;Griffin JL;Feskens EJ;Affret A;Amiano P;Boeing H;Dow C;Fagherazzi G;Franks PW;Gonzalez C;Kaaks R;Key TJ;Khaw KT;Kühn T;Mortensen LM;Nilsson PM;Overvad K;Pala V;Palli D;Panico S;Quirós JR;Rodriguez-Barranco M;Rolandsson O;Sacerdote C;Scalbert A;Slimani N;Spijkerman AM;Tjonneland A;Tormo MJ;Tumino R;van der A DL;van der Schouw YT;Langenberg C;Riboli E;Wareham NJ
n-3和n-6多不饱和脂肪酸（PUFA）是否以及如何与2型糖尿病（T2 D）相关仍有争议。客观测量的血浆PUFAs可以帮助澄清这些关联。在欧洲癌症与营养前瞻性研究（EPIC）-InterAct研究中，通过气相色谱法测量了8个欧洲国家的12，132例T2 D事件病例和15，919例亚队列参与者的血浆磷脂PUFA。使用Prentice加权考克斯回归估计国家特异性风险比（HR），并通过随机效应荟萃分析汇总。我们还系统地回顾了已发表的关于循环PUFA和T2 D风险的前瞻性研究，并汇总了定量证据，以与EPIC-InterAct的结果进行比较。在EPIC-InterAct中，在长链n-3 PUFA中，α-亚麻酸（ALA）与T2 D呈负相关（HR/标准差[SD] 0.93; 95% CI 0.88-0.98），但二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）无显著相关性。在n-6 PUFA中，亚油酸（LA）（0.80; 95% CI 0.77-0.83）和二十碳二烯酸（EDA）（0.89; 95%CI 0.85-0.94）呈负相关，花生四烯酸（AA）无显著相关性，而γ-亚麻酸（GLA）、二高-GLA、二十二碳四烯酸（DTA）、和二十二碳五烯酸（n6-DPA），HR在1.13至1.46/SD之间。EPIC-InterAct的这些结果与来自多达9项研究（包括71至2，499例T2 D病例）的汇总估计的比较结果大致相似。局限性包括潜在残留混杂和无法区分饮食和代谢对血浆磷脂PUFA的影响。这些大规模的研究结果表明，循环植物来源的n-3 PUFA（ALA）存在重要的负相关性，但海洋来源的n3 PUFA（EPA和DHA）与T2 D没有令人信服的关联。此外，他们强调，最丰富的n6-PUFA（LA）与T2 D呈负相关。与以前研究较少的PUFA的相关性的检测指出了考虑单个脂肪酸而不是关注脂肪酸类别的重要性。Nita Forouhi及其同事利用一个大型欧洲队列研究了血浆中多不饱和脂肪酸浓度与2型糖尿病风险之间的关系。大多数膳食指南建议消费多不饱和脂肪酸对心血管健康，但目前尚不清楚n-3和n-6型多不饱和脂肪酸是否或如何与2型糖尿病有关。以前曾有人对高亚油酸（n-6脂肪酸）饮食提出健康问题，但其与2型糖尿病的关系尚不清楚。以往研究的主要局限性包括：在评估膳食摄入量时，对多不饱和脂肪酸的习惯性消费进行了容易出错的主观评估，以及在测量多不饱和脂肪酸的客观生物标志物时，对少数2型糖尿病病例（n = 71至673）进行了评估。我们测量了来自欧洲八个国家的一项大型研究中个体血液样本中的循环个体多不饱和脂肪酸，其中参考样本为15，919名个体以及随后发展为糖尿病的12，132名个体。个体平均随访约10年。我们调查了个体多不饱和脂肪酸与未来2型糖尿病风险之间的关联，使用统计分析来解释可能是任何观察到的关联的潜在替代解释的因素。我们发现，血液中α-亚麻酸（一种植物来源的n-3脂肪酸）和n-6亚油酸（一种最丰富的多不饱和脂肪酸）水平较高，与未来患2型糖尿病的风险较低相关。相比之下，其他四种微量n-6脂肪酸的水平较高与2型糖尿病风险较高相关，而血液中海洋来源的n-3脂肪酸与未来的糖尿病无关。我们的研究结果表明，重要的是要考虑个人循环多不饱和脂肪酸与2型糖尿病风险的关联，而不是把重点放在循环多不饱和脂肪酸的类别。我们发现，血液中n-6亚油酸，最丰富的多不饱和脂肪酸，与2型糖尿病呈负相关。我们没有发现血液中总n-6多不饱和脂肪酸可能增加2型糖尿病的风险的证据，但几种单独的微量血液n-6多不饱和脂肪酸与2型糖尿病风险增加有关，突出了多不饱和脂肪酸代谢在2型糖尿病发展中的重要性。
Whether 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. Plasma 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. These 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. Using a large European cohort, Nita Forouhi and colleagues investigate the association between the concentration of polyunsaturated fatty acids measured in plasma and risk of developing type 2 diabetes. Most dietary guidelines recommend the consumption of polyunsaturated fatty acids for cardiovascular health, but it is unclear whether or how n-3 and n-6 types of polyunsaturated fatty acids are related to type 2 diabetes. Health concerns have been raised previously about a diet high in linoleic acid (n-6 fatty acid), but its association with type 2 diabetes is unclear. Major limitations in previous studies have included the error-prone subjective assessment of the habitual consumption of polyunsaturated fatty acids when dietary intakes were evaluated and a small number of type 2 diabetes cases (n = 71 to 673) when objective biomarkers of polyunsaturated fatty acids were measured. We measured circulating individual polyunsaturated fatty acids in the blood samples of individuals within a large study from across eight countries of Europe among a reference sample of 15,919 individuals as well as 12,132 individuals who subsequently developed diabetes. Individuals were followed up for an average of approximately 10 y. We investigated the association between individual polyunsaturated fatty acids and the risk of future type 2 diabetes using statistical analyses that accounted for factors that could be potential alternative explanations for any observed associations. We found that higher levels of blood alpha-linolenic acid, a plant-origin n-3 fatty acid, and n-6 linoleic acid, the most abundant type of polyunsaturated fatty acid, were associated with a lower risk of future type 2 diabetes. In contrast, higher levels of four other minor individual n-6 fatty acids were associated with higher type 2 diabetes risk, while the blood marine-origin n-3 fatty acids were not associated with future diabetes. Our findings show that it is important to consider individual circulating polyunsaturated fatty acids for association with type 2 diabetes risk, rather than placing emphasis on the class of circulating polyunsaturated fatty acids. We found that blood n-6 linoleic acid, the most abundant polyunsaturated fatty acid, is inversely associated with type 2 diabetes. We found no evidence that blood total n-6 polyunsaturated fatty acids may elevate the risk of type 2 diabetes, but several individual minor blood n-6 polyunsaturated fatty acids were associated with increased type 2 diabetes risk, highlighting the importance of polyunsaturated fatty acid metabolism in the development of type 2 diabetes.