title: Relationship of Serum Trimethylamine N-Oxide (TMAO) Levels with early Atherosclerosis in Humans.
abstract: Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.40, p < 0.0001), liver fat content (r = 0.23, p = 0.0005) and TMAO levels (r = 0.26, p < 0.0001) associated positively, and insulin sensitivity associated negatively (r = -0.18, p = 0.009) with carotid intima-media thickness (cIMT). Higher TMAO levels (std.-Beta 0.11, p = 0.03) predicted increased cIMT, independently of age, sex and visceral fat mass. While during the lifestyle intervention most cardiovascular risk parameters improved, mean TMAO levels did not change (p = 0.18). However, cIMT decreased significantly (p = 0.0056) only in subjects in the tertile with the largest decrease of TMAO levels (>20%). We provide novel information that increased serum TMAO levels associate with increased cIMT, independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention may be related to the decrease of TMAO levels.
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
authors.forename: Elko
authors.initials: E
authors.lastname: Randrianarisoa
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Lehn-Stefan
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hoene
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peter
authors.affiliation: German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.|Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Silke S
authors.initials: SS
authors.lastname: Heinzmann
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Tübingen, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Königsrainer
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Tübingen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Balletshofer
authors.affiliation: Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.affiliation: Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.|Section on Experimental Radiology, University of Tübingen, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehmann
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
mesh_terms: D050154:Adiposity; D000328:Adult; D050197:Atherosclerosis / Q000097:blood*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D008744:Methylamines; C005855:trimethyloxamine