Background

Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.

Methods and findings

We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991–1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19–0.29) adjusted for potential confounders and 0.37 (95% CI 0.27–0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.

Conclusions

A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

中文翻译：

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血浆磷脂脂肪酸的组合及其与2型糖尿病发病率的关系：EPIC-InterAct病例队列研究

背景

多种脂肪酸的组合可能比单一脂肪酸对心脏代谢风险的影响更大。尚未评估脂肪酸组合与2型糖尿病（T2D）的关联。

方法和发现

我们采用基线分析（1991-1998年）至2007年12月31日在欧洲8个国家的EPIC-InterAct中通过气相色谱法对27,296名成年人（包括12,132例T2D事件）中的血浆磷脂脂肪酸进行了测量，这是一个嵌套案例，队列研究。主要暴露量是通过对27种单独脂肪酸（摩尔百分比）进行主成分分析得出的第一个主成分（随后称为脂肪酸模式评分[FA-pattern score]）。FA模式得分的部分特征是高浓度的亚油酸，硬脂酸，奇数链脂肪酸和超长链饱和脂肪酸，以及低浓度的γ-亚麻酸，棕榈酸和长链单不饱和脂肪酸脂肪酸，它解释了27种脂肪酸的总变异性的16.1％。基于特定国家/地区的Prentice加权Cox回归和随机效应荟萃分析，FA模式得分与较低的T2D事件相关。比较得分的最高和最低的五分之一，针对潜在混杂因素调整的事件T2D的风险比为0.23（95％CI 0.19-0.29），对于代谢风险因素进一步调整为0.37（95％CI 0.27-0.50）。在调整了个别脂肪酸或脂肪酸亚类后，该关联变化不大。在将FA模式评分与代谢，遗传和饮食因素相关的横断面分析中，FA模式评分与肥胖，甘油三酸酯，肝酶，C反应蛋白，代表胰岛素抵抗的遗传评分，p < 0.05）。局限性包括脂肪酸和其他模型协变量中潜在的测量误差以及可能的残留混杂。

结论

以高浓度的亚油酸，奇数链脂肪酸和长链脂肪酸为特征的单个脂肪酸的组合与T2D的发生率较低相关。特定的脂肪酸模式可能会受到代谢，遗传和饮食因素的影响。