A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control

Noha A. Yousri, Dennis O. Mook-Kanamori, Mohammed M.El Din Selim, Ahmed H. Takiddin, Hala Al-Homsi, Khoulood A.S. Al-Mahmoud, Edward D. Karoly, Jan Krumsiek, Kieu Thinh Do, Ulrich Neumaier, Marjonneke J. Mook-Kanamori, Jillian Rowe, Omar M. Chidiac, Cindy McKeon, Wadha A. Al Muftah, Sara Abdul Kader, Gabi Kastenmüller, Karsten Suhre

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaemic control is still lacking. Methods: Here we report a broad metabolomics study in a clinical setting, covering 2,178 metabolite measures in saliva, blood plasma and urine from 188 individuals with diabetes and 181 controls of Arab and Asian descent. Using multivariate linear regression we identified metabolites associated with diabetes and markers of acute, short-term and long-term glycaemic control. Results: Ninety-four metabolite associations with diabetes were identified at a Bonferroni level of significance (p < 2.3 × 10−5), 16 of which have never been reported. Sixty-five of these diabetes-associated metabolites were associated with at least one marker of glycaemic control in the diabetes group. Using Gaussian graphical modelling, we constructed a metabolic network that links diabetes-associated metabolites from three biofluids across three different timescales of glycaemic control. Conclusions/interpretation: Our study reveals a complex network of biochemical dysregulation involving metabolites from different pathways of diabetes pathology, and provides a reference framework for future diabetes studies with metabolic endpoints.

Original languageEnglish (US)
Pages (from-to)1855-1867
Number of pages13
JournalDiabetologia
Volume58
Issue number8
DOIs
StatePublished - Aug 23 2015

Keywords

  • Arab population
  • Asian population
  • Blood metabolomics
  • Gaussian graphical modelling
  • Glycaemic control
  • Metabolic dysregulation
  • Partial correlation
  • Saliva metabolomics
  • Systems biology
  • Type 2 diabetes
  • Urine metabolomics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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