title: Metabolic Fingerprints of Circulating IGF-1 and the IGF-1/IGFBP-3 Ratio: A Multifluid Metabolomics Study.
abstract: IGF-1 is known for its various physiological and severe pathophysiological effects on human metabolism; however, underlying molecular mechanisms still remain unsolved. To reveal possible molecular mechanisms mediating these effects, for the first time, we associated serum IGF-1 levels with multifluid untargeted metabolomics data.
  
  
  
  Plasma/urine samples of 995 nondiabetic participants of the Study of Health in Pomerania were characterized by mass spectrometry. Sex-specific linear regression analyses were performed to assess the association of IGF-1 and IGF-1/IGF binding protein 3 ratio with metabolites. Additionally, the predictive ability of the plasma and urine metabolome for IGF-1 was assessed by orthogonal partial least squares analyses.
  
  
  
  We revealed a multifaceted image of associated metabolites with large sex differences. Confirming previous reports, we detected relations between IGF-1 and steroid hormones or related intermediates. Furthermore, various associated metabolites were previously mentioned regarding IGF-1-associated diseases, eg, betaine and cortisol in cardiovascular disease and metabolic syndrome, lipid disorders, and diabetes, or have previously been found to associate with differentiation and proliferation or mitochondrial functionality, eg, phospholipids. bradykinin, fatty acid derivatives, and cortisol, which were inversely associated with IGF-1, might establish a link of IGF-1 with inflammation. For the first time, we showed an association between IGF-1 and pipecolate, a metabolite linked to amino acid metabolism. Our study demonstrates that IGF-1 action on metabolism is tractable, even in healthy subjects, and that the findings provide a solid basis for further experimental/clinical investigation, eg, searching for inflammatory or cardiovascular disease- or metabolic syndrome-associated biomarkers and therapeutic targets.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Henrike
authors.initials: H
authors.lastname: Knacke
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Maik
authors.initials: M
authors.lastname: Pietzner
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Kieu Trinh
authors.initials: KT
authors.lastname: Do
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Werner
authors.initials: W
authors.lastname: Römisch-Margl
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Artati
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine (H.K., M.P., H.W., M.N., N.F.) and Institute for Community Medicine (H.V.), University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine and Ernst-Moritz Arndt-University Greifswald, and German Center for Cardiovascular Research (M.N., N.F.), partner site Greifswald, 17475 Greifswald, Germany; Institute of Computational Biology (K.T.D., J.K., K.S.), Helmholtz-Zentrum München, and German Center for Diabetes Research (J.K.), and Institute of Bioinformatics and Systems Biology (W.R.-M., G.K.), Helmholtz Zentrum München, German Research Center for Environmental Health, and Institute of Experimental Genetics (A.A., J.A.), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany, and German Center for Diabetes Research (J.A.), 85764 München-Neuherberg, Germany; Schwerpunktpraxis für Diabetes und Hormonerkrankungen (H.W.), 99094 Erfurt, Germany; Weill Cornell Medical College in Qatar (K.S.), Education City, Qatar Foundation, Doha, Qatar; Lehrstuhl für Experimentelle Genetik (J.A.), Technische Universität München, 85350 Freising-Weihenstephan, Germany; Research Centre for Prevention and Health (N.F.), Capital Region of Denmark, 2600 Glostrup, Denmark.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D012042:Registries; D012737:Sex Factors; D055815:Young Adult
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I