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Sex differences in urine metabolites related with risk of diabetes using NMR spectroscopy: results of the study of health in pomerania

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Abstract

Recently research provides evidence that blood metabolite profiles predicted type 2 diabetes. We aimed to assess the relation of urine metabolites measured via nuclear magnetic resonance spectroscopy with incident type 2 diabetes in a sample of 1353 men and 1356 women. Within 5 years, 87 men and 50 women developed diabetes. Five and 16 urine metabolites were associated with incident diabetes in men and women, respectively. Only three of these metabolites (glucose, lactate and glycine) were found in both sexes. In women, e.g. acetate, carnitine, N,N-dimethylglycine, trigonelline, 3-hydroxyisovalerate, alanine, formate, glycolate, trimethylamine N-oxide and tau-methylhistidine were positively related with diabetes. Receiver operating characteristic (ROC) analysis revealed that compared with a standard model, a model additionally adjusted for urine glucose, trigonelline and trimethylamine N-oxide levels showed a better discrimination between incident diabetes cases and non-cases in women (AUC = 0.874 and 0.903, p = 0.019). In men, valine and 4-hydroxyphenylacetate were found as markers of diabetes. However, ROC analysis did not reveal any improvement in discrimination based on urine metabolites. In conclusion, we confirmed the potential of metabolomics to assess the risk of type 2 diabetes and detected pronounced sex differences. Moreover, we demonstrated the practicability of spot urine samples as potential non-invasive diabetes screening approach.

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Acknowledgments

SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (Grant Nos. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Preparation and NMR measurement was supported by Bruker BioSpin GmbH Rheinstetten, Germany. This work is also part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg—West Pomerania (03IS2061A).

Conflict of interest

The authors declare that they have no conflict of interest.

Compliance with ethical requirements

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. NK, 17475, Greifswald, Germany

    Nele Friedrich, Kathrin Budde, Matthias Nauck & Henri Wallaschofski

  2. DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany

    Nele Friedrich, Uwe Völker, Stephan B. Felix, Matthias Nauck & Henri Wallaschofski

  3. Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Karsten Suhre

  4. Department of Physiology and Biophysics, Weill Cornell Medical College, Ar-Rayyan, Qatar

    Karsten Suhre

  5. Institute of Functional Genomics, University Medicine Greifswald, Greifswald, Germany

    Uwe Völker

  6. Institute of Epidemiology and Social Medicine, University Medicine Greifswald, Greifswald, Germany

    Ulrich John

  7. Department of Cardiology, University Medicine Greifswald, Greifswald, Germany

    Stephan B. Felix

  8. Georg-August University, University Medicine Göttingen, Göttingen, Germany

    Heyo K. Kroemer

  9. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Greifswald, Germany

    Hans J. Grabe

  10. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    Henry Völzke

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  1. Nele Friedrich
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Correspondence to Nele Friedrich.

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Friedrich, N., Budde, K., Suhre, K. et al. Sex differences in urine metabolites related with risk of diabetes using NMR spectroscopy: results of the study of health in pomerania. Metabolomics 11, 1405–1415 (2015). https://doi.org/10.1007/s11306-015-0795-6

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