红细胞膜磷脂脂肪酸、去饱和酶活性与膳食脂肪酸与欧洲癌症前瞻性调查与营养（EPIC）-波茨坦研究中 2 型糖尿病风险的关系。

Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.

机构信息

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.

出版信息

Am J Clin Nutr. 2011 Jan;93(1):127-42. doi: 10.3945/ajcn.110.005447. Epub 2010 Oct 27.

DOI:10.3945/ajcn.110.005447

PMID:20980488

Abstract

BACKGROUND

The long-term role of fatty acids (FAs) in the cause of diabetes remains largely unclear.

OBJECTIVE

We aimed to investigate erythrocyte membrane FAs, desaturase activity, and dietary FAs in relation to the incidence of type 2 diabetes.

DESIGN

We applied a nested case-cohort design (n = 2724, including 673 incident diabetes cases) within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, which involves 27,548 middle-aged subjects. Thirty erythrocyte membrane FAs (percentage of total FAs) and FA intake (percentage of total fat) were measured at baseline, and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 y. We evaluated Δ⁵ desaturase (D5D) and Δ⁶ desaturase (D6D) activity by using FA product-to-precursor ratios (traditional approach) and by investigating variants in FADS1 and FADS2 genes that encode these desaturases (Mendelian randomization approach).

RESULTS

As a main finding, erythrocyte 16:1n-7 and 18:3n-6 and FA ratios, which reflect stearoyl coenzyme A desaturase (SCD) and D6D activity, were directly related to diabetes risk in multivariable-adjusted models [relative risks (95% CIs) comparing extreme quintiles: 16:1n-7, 2.11 (1.46, 3.05); 18:3n-6, 2.00 (1.38, 2.88); SCD, 2.61 (1.75, 3.89); and D6D, 2.46 (1.67, 3.63)], whereas the FA ratio that reflects D5D activity was inversely associated with risk [0.46 (0.31, 0.70)]. The Mendelian randomization approach corroborated the direct relation for D6D activity and tended to support the inverse relation for D5D activity. Proportions of dietary FAs showed only modest to low correlations with erythrocyte FAs and were not significantly associated with risk.

CONCLUSION

The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes.

摘要

背景

脂肪酸（FAs）在糖尿病发病中的长期作用在很大程度上仍不清楚。

目的

我们旨在研究红细胞膜 FAs、去饱和酶活性和膳食 FAs 与 2 型糖尿病发病的关系。

设计

我们在欧洲癌症前瞻性调查与营养研究（EPIC）-波茨坦研究中应用了巢式病例对照设计（n = 2724，包括 673 例新发糖尿病病例），该研究涉及 27548 名中年受试者。在基线时测量了 30 种红细胞膜 FAs（总 FAs 的百分比）和 FA 摄入量（总脂肪的百分比），并在平均 7.0 年的随访期间评估了经医生确诊的新发糖尿病。我们通过使用 FA 产物与前体的比值（传统方法）和通过研究编码这些去饱和酶的 FADS1 和 FADS2 基因中的变异（孟德尔随机化方法）来评估 Δ⁵去饱和酶（D5D）和 Δ⁶去饱和酶（D6D）活性。

结果

作为主要发现，红细胞 16:1n-7 和 18:3n-6 以及反映硬脂酰辅酶 A 去饱和酶（SCD）和 D6D 活性的 FA 比值与多变量调整模型中的糖尿病风险直接相关[比较极端五分位数的相对风险（95%置信区间）：16:1n-7，2.11（1.46，3.05）；18:3n-6，2.00（1.38，2.88）；SCD，2.61（1.75，3.89）；D6D，2.46（1.67，3.63）]，而反映 D5D 活性的 FA 比值与风险呈负相关[0.46（0.31，0.70）]。孟德尔随机化方法证实了 D6D 活性的直接关系，并倾向于支持 D5D 活性的反比关系。膳食 FAs 的比例与红细胞 FAs 只有适度到低度的相关性，且与风险无显著相关性。