title: Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts.
abstract: BACKGROUND
  Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH).
  
  
  METHODS
  Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function.
  
  
  RESULTS
  Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values.
  
  
  CONCLUSIONS
  The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research.
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, Denmark.|Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Pietzner
authors.affiliation: Bruker BioSpin, Rheinstetten, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Cannet
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, Denmark.
authors.forename: Betina H
authors.initials: BH
authors.lastname: Thuesen
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.|Private Practice Endocrinology, Erfurt, Germany.
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, Denmark.
authors.forename: Tea
authors.initials: T
authors.lastname: Skaaby
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Budde
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, Denmark.|Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003069:Coffee; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D013960:Thyroid Function Tests
chemical_list: D001786:Blood Glucose; D003069:Coffee