Comprehensive metabolomics study to assess longitudinal biochemical changes and potential early biomarkers in nonobese diabetic mice that progress to diabetes

Peter Buchwald, Alejandro Tamayo-Garcia, Sivapriya Ramamoorthy, Marta Garcia-Contreras, Armando J Mendez, Camillo Ricordi

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

A global nontargeted longitudinal metabolomics study was carried out in male and female NOD mice to characterize the timeprofile of the changes in the metabolic signature caused by onset of type 1 diabetes (T1D) and identify possible early biomarkers in T1D progressors. Metabolomics profiling of samples collected at five different time-points identified 676 and 706 biochemicals in blood and feces, respectively. Several metabolites were expressed at significantly different levels in progressors at all time-points, and their proportion increased strongly following onset of hyperglycemia. At the last time-point, when all progressors were diabetic, a large percentage of metabolites had significantly different levels: 57.8% in blood and 27.8% in feces. Metabolic pathways most strongly affected included the carbohydrate, lipid, branched-chain amino acid, and oxidative ones. Several biochemicals showed considerable (>4×) change. Maltose, 3-hydroxybutyric acid, and kojibiose increased, while 1,5- anhydroglucitol decreased more than 10-fold. At the earliest time-point (6-week), differences between the metabolic signatures of progressors and nonprogressors were relatively modest. Nevertheless, several compounds had significantly different levels and show promise as possible early T1D biomarkers. They include fatty acid phosphocholine derivatives from the phosphatidylcholine subpathway (elevated in both blood and feces) as well as serotonin, ribose, and arabinose (increased) in blood plus 13-HODE, tocopherol (increased), diaminopimelate, valerate, hydroxymethylpyrimidine, and dulcitol (decreased) in feces. A combined metabolic signature based on these compounds might serve as an early predictor of T1D-progressors.

Original languageEnglish (US)
Pages (from-to)3873-3890
Number of pages18
JournalJournal of Proteome Research
Volume16
Issue number10
DOIs
StatePublished - Oct 6 2017

Keywords

  • 5-anhydroglucitol
  • Beta hydroxybutyric acid
  • Branched-chain amino acids
  • Diabetes mellitus
  • Gender differences
  • Hyperglycemia
  • Kojibiose
  • Metabolomics
  • Nonobese diabetic (nod) mice
  • Sorbitol

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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