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.
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.
Authors: Maria A Lankinen; Alena Stančáková; Matti Uusitupa; Jyrki Ågren; Jussi Pihlajamäki; Johanna Kuusisto; Ursula Schwab; Markku Laakso Journal: Diabetologia Date: 2015-08-16 Impact factor: 10.122
Authors: Jason H Y Wu; Renata Micha; Fumiaki Imamura; An Pan; Mary L Biggs; Owais Ajaz; Luc Djousse; Frank B Hu; Dariush Mozaffarian Journal: Br J Nutr Date: 2012-06 Impact factor: 3.718
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Authors: Markus J Takkunen; Ursula S Schwab; Vanessa D F de Mello; Johan G Eriksson; Jaana Lindström; Jaakko Tuomilehto; Matti I J Uusitupa Journal: Eur J Nutr Date: 2015-05-01 Impact factor: 5.614
Authors: S Jacobs; K Schiller; E Jansen; A Fritsche; C Weikert; R di Giuseppe; H Boeing; M B Schulze; J Kröger Journal: Eur J Clin Nutr Date: 2014-02-26 Impact factor: 4.016
Authors: Hemant Kulkarni; Peter J Meikle; Manju Mamtani; Jacquelyn M Weir; Christopher K Barlow; Jeremy B Jowett; Claire Bellis; Thomas D Dyer; Matthew P Johnson; David L Rainwater; Laura Almasy; Michael C Mahaney; Anthony G Comuzzie; John Blangero; Joanne E Curran Journal: Lipids Date: 2013-03-14 Impact factor: 1.880