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Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes

Allison L. O’Kell, Timothy J. Garrett, Clive Wasserfall, Mark A. Atkinson
doi: https://doi.org/10.1101/139113
Allison L. O’Kell
aDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Florida, Gainesville, Florida, USA
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Timothy J. Garrett
bDepartment of Pathology, Immunology, and Laboratory Medicine, The University of Florida, Gainesville, Florida, USA
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Clive Wasserfall
bDepartment of Pathology, Immunology, and Laboratory Medicine, The University of Florida, Gainesville, Florida, USA
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Mark A. Atkinson
bDepartment of Pathology, Immunology, and Laboratory Medicine, The University of Florida, Gainesville, Florida, USA
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Abstract

While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n=6) and healthy (n=6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of known and unknown metabolites. Random forest classification identified 5/6 dogs per group correctly with overall out of bag error rate=16.7%. Diabetic dogs demonstrated significant upregulation of glycolysis/gluconeogenesis intermediates (e.g., glucose/fructose, C6H12O6, keto-hexose, deoxy-hexose, (P<0.01)), with significant downregulation of tryptophan metabolism metabolites (e.g., picolinic acid, indoxyl sulfate, anthranilate, (P<0.01)). Multiple amino acids (AA), AA metabolites, and bile acids were also significantly lower in diabetic versus healthy dogs (P<0.05) with the exception of the branched chain AA valine, which was elevated in diabetic animals (P<0.05). Metabolomic profiles in diabetic versus healthy dogs shared similarities with those reported in human T1D (e.g., alterations in glycolysis/gluconeogensis metabolites, bile acids, and elevated branched chain AA). Further studies are warranted to evaluate the utility of canine diabetes to provide novel mechanistic insights to the human disorder.

AA
(amino acid)
AAb
(autoantibody)
FA
(fatty acid)
HILIC
(hydrophilic interaction liquid interaction chromatography)
LC-MS
(liquid chromatography mass spectrometry)
OOB
(out of bag)
T1D
(type 1 diabetes)
T2D
(type 2 diabetes)
UF
(University of Florida)
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 17, 2017.
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Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes
Allison L. O’Kell, Timothy J. Garrett, Clive Wasserfall, Mark A. Atkinson
bioRxiv 139113; doi: https://doi.org/10.1101/139113
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Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes
Allison L. O’Kell, Timothy J. Garrett, Clive Wasserfall, Mark A. Atkinson
bioRxiv 139113; doi: https://doi.org/10.1101/139113

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