title: Metabolomic Signature of Coronary Artery Disease in Type 2 Diabetes Mellitus.
abstract: Coronary artery disease (CAD) is a common complication of type 2 diabetes mellitus (T2D). This case-control study was done to identify metabolites with different concentrations between T2D patients with and without CAD and to characterise implicated metabolic mechanisms relating to CAD. Fasting serum samples of 57 T2D subjects, 26 with (cases) and 31 without CAD (controls), were targeted for metabolite profiling of 163 metabolites. To assess the association between metabolite levels and CAD, partial least squares (PLS) analysis and multivariate logistic regression analysis with adjustment for CAD risk factors and medications were performed. We observed a separation of cases and controls with two classes of metabolites being significantly associated with CAD, including phosphatidylcholines, and serine. Four metabolites being independent from the common CAD risk factors displaying best separation between cases and controls were further selected. Addition of the metabolite concentrations to risk factor analysis raised the area under the receiver-operating-characteristic curve from 0.72 to 0.88 (p= 0.020), providing improved sensitivity and specificity for CAD classification. Serum phospholipid and serine levels independently discriminate T2D patients with and without CAD. Oxidative stress and reduced antioxidative capacity lead to lower metabolite concentrations probably due to changes in membrane composition and accelerated phospholipid degradation.
authors.affiliation: Herz- und Diabeteszentrum NRW, Ruhr-Universitaet Bochum, Diabeteszentrum, 32545 Bad Oeynhausen, Germany.
authors.forename: Bernd
authors.identifier: 0000-0001-5777-3715
authors.initials: B
authors.lastname: Stratmann
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Richter
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Ruichao
authors.initials: R
authors.lastname: Wang
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Experimental Genetics, Life and Food Science Center Weihenstephan, Technische Universität München, 85354 Freising, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Thomas
authors.identifier: 0000-0003-4284-5389
authors.initials: T
authors.lastname: Illig
authors.affiliation: Herz- und Diabeteszentrum NRW, Ruhr-Universitaet Bochum, Diabeteszentrum, 32545 Bad Oeynhausen, Germany.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschoepe
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler