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
AMERICAN JOURNAL OF CLINICAL NUTRITION
Authors: Kroeger, Janine; Zietemann, Vera; Enzenbach, Cornelia; Weikert, Cornelia; Jansen, Eugene H. J. M.; Doering, Frank; Joost, Hans-Georg; Boeing, Heiner; Schulze, Matthias B.
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 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.
Plasma fatty acids as predictors of glycaemia and type 2 diabetes
DIABETOLOGIA
Authors: Lankinen, Maria A.; Stancakova, Alena; Uusitupa, Matti; Agren, Jyrki; Pihlajamaki, Jussi; Kuusisto, Johanna; Schwab, Ursula; Laakso, Markku
Abstract
Aims/hypothesis Our aim was to investigate the fasting proportions of fatty acids and estimated desaturase and elongase activities in three different lipid fractions in plasma, phospholipids (PLs), cholesteryl esters (CEs) and triacylglycerols (TGs), as predictors for the worsening of glycaemia (area under the glucose curve in an OGTT [glucose AUC]) and incident type 2 diabetes in a 5.9 year follow-up of the Metabolic Syndrome in Men population-based cohort. Methods Fatty acid proportions were measured in plasma PL, CE and TG fractions in 1,364 Finnish men aged 45-68 years at baseline. The prospective follow-up study included only men who were non-diabetic at baseline and had data available at follow-up (n = 1,302). A total of 71 participants developed new type 2 diabetes during follow-up. Results After adjusting for confounding factors, total saturated fatty acids, palmitoleic acid (16:1n-7), dihomo-gamma-linolenic acid (20:3n-6) and estimated stearoyl-CoA desaturase 1 and Delta(6)-desaturase (D6D) enzyme activities significantly predicted the worsening of glycaemia whereas total polyunsaturated fatty acid, linoleic acid (18:2n-6) and elongase activity predicted a decrease in the glucose AUC. Estimated D6D activity and dihomo-gamma-linolenic acid (20:3n-6) were associated with an increased risk of incident type 2 diabetes. Results were consistent across the three different lipid fractions. However, fatty acid proportions in the PL and CE fractions were stronger predictors for glycaemia and incident type 2 diabetes compared with fatty acid proportions in the TG fraction. Conclusions/interpretation Selected fatty acid proportions of plasma lipid fractions and their ratios, which reflect desaturase and elongase enzyme activities, may be good biomarkers for the worsening of glycaemia and incident type 2 diabetes.