Evaluation of various biomarkers as potential mediators of the association between Δ5 desaturase, Δ6 desaturase, and stearoyl-CoA desaturase activity and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition–Potsdam Study

Abstract

An association between desaturase activity and risk of type 2 diabetes (T2D) has been found in epidemiologic studies, but little is known about potential mediators of this association. We aimed to investigate the potential role of diabetes-related biomarkers as mediators of the association between estimated Δ5 desaturase (D5D), Δ6 desaturase (D6D), and stearoyl-CoA desaturase (SCD) activity and T2D risk. We analyzed a case-cohort study (subcohort: n = 1533; verified incident T2D cases: n = 400), nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam Study involving 27,548 middle-aged participants. We evaluated the impact of adjustment for several T2D-related biomarkers reflecting liver fat accumulation [reflected by γ-glutamyltransferase (GGT), alanine transaminase (ALT), fetuin-A, and the algorithm-based fatty liver index (FLI)], dyslipidemia (high-density lipoprotein cholesterol, triglycerides), inflammation [C-reactive protein (CRP)], and adiponectin on the association between D5D, D6D, and SCD activity, estimated with fatty acid product-to-precursor ratios derived from erythrocyte membrane proportions, and T2D risk. Estimated D5D activity was inversely associated with T2D risk, whereas D6D and SCD activities were positively associated with risk of T2D [HRs (95% CIs) (highest vs. lowest tertile): 0.51 (0.36, 0.73), 1.68 (1.18, 2.39), and 1.82 (1.29, 2.58), respectively]. The association between estimated D5D, D6D, and SCD activities and risk of T2D was statistically significantly and markedly attenuated after adjustment for the FLI and, to a lesser extent, after adjustment for triglycerides, whereas adjustment for other desaturase-associated biomarkers (CRP, fetuin-A, ALT, and GGT) did not lead to appreciable attenuations. Liver fat accumulation, as reflected by the FLI, and dyslipidemia, as reflected by triglycerides, may partly explain the association between estimated D5D, D6D, and SCD activity and T2D risk.