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

被引:218
作者
Kroeger, Janine [1 ,2 ]
Zietemann, Vera [4 ]
Enzenbach, Cornelia [4 ]
Weikert, Cornelia [2 ]
Jansen, Eugene H. J. M. [5 ]
Doering, Frank [6 ]
Joost, Hans-Georg [3 ]
Boeing, Heiner [2 ]
Schulze, Matthias B. [1 ,2 ,4 ]
机构
[1] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, D-14558 Nuthetal, Germany
[2] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, D-14558 Nuthetal, Germany
[3] German Inst Human Nutr Potsdam Rehbrucke, Dept Pharmacol, D-14558 Nuthetal, Germany
[4] Tech Univ Munich, Publ Hlth Nutr Unit, D-8050 Freising Weihenstephan, Germany
[5] Natl Inst Publ Hlth & Environm, Lab Hlth Protect Res, NL-3720 BA Bilthoven, Netherlands
[6] Univ Kiel, Inst Human Nutr & Food Sci, Dept Mol Nutr, Kiel, Germany
关键词
STEAROYL-COA DESATURASE; IMPAIRED GLUCOSE-TOLERANCE; FADS1-FADS2; GENE-CLUSTER; TOTAL-ENERGY INTAKE; INSULIN SENSITIVITY; MENDELIAN RANDOMIZATION; EPIC PROJECT; METABOLIC SYNDROME; LINOLEIC-ACID; GERMAN PART;
D O I
10.3945/ajcn.110.005447
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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 Delta(5) desaturase (D5D) and Delta(6) 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 16:1n27 and 18:3n26 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: 16:1n27, 2.11 (1.46, 3.05); 18:3n26, 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. Am J Clin Nutr 2011;93:127-42.
引用
收藏
页码:127 / 142
页数:16
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