title: A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation - Education City, PO Box 24144, Doha, Qatar.
authors.forename: Noha A
authors.initials: NA
authors.lastname: Yousri
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Mook-Kanamori
authors.forename: Mohammed M El-Din
authors.initials: MM
authors.lastname: Selim
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Takiddin
authors.forename: Hala
authors.initials: H
authors.lastname: Al-Homsi
authors.forename: Khoulood A S
authors.initials: KA
authors.lastname: Al-Mahmoud
authors.forename: Edward D
authors.initials: ED
authors.lastname: Karoly
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.forename: Kieu Trinh
authors.initials: KT
authors.lastname: Do
authors.forename: Kieu Thinh
authors.initials: KT
authors.lastname: Do
authors.forename: Ulrich
authors.initials: U
authors.lastname: Neumaier
authors.forename: Marjonneke J
authors.initials: MJ
authors.lastname: Mook-Kanamori
authors.forename: Jillian
authors.initials: J
authors.lastname: Rowe
authors.forename: Omar M
authors.initials: OM
authors.lastname: Chidiac
authors.forename: Cindy
authors.initials: C
authors.lastname: McKeon
authors.forename: Wadha A
authors.initials: WA
authors.lastname: Al Muftah
authors.forename: Sara Abdul
authors.initials: SA
authors.lastname: Kader
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose