Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus

Xinyun Gu; Mohammed Al Dubayee; Awad Alshahrani; Afshan Masood; Hicham Benabdelkamel; Mahmoud Zahra; Liang Li; Anas M Abdel Rahman; Ahmad Aljada

doi:10.3389/fmolb.2020.609806

Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus

Front Mol Biosci. 2020 Dec 14:7:609806. doi: 10.3389/fmolb.2020.609806. eCollection 2020.

Authors

Affiliations

¹ Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
² Department of Medicine, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
³ Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁴ Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁵ Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁶ Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, Canada.

Abstract

Obesity is associated with an increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) which is a multi-factorial disease associated with a dysregulated metabolism and can be prevented in pre-diabetic individuals with impaired glucose tolerance. A metabolomic approach emphasizing metabolic pathways is critical to our understanding of this heterogeneous disease. This study aimed to characterize the serum metabolomic fingerprint and multi-metabolite signatures associated with IR and T2DM. Here, we have used untargeted high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) to identify candidate biomarkers of IR and T2DM in sera from 30 adults of normal weight, 26 obese adults, and 16 adults newly diagnosed with T2DM. Among the 3633 peak pairs detected, 62% were either identified or matched. A group of 78 metabolites were up-regulated and 111 metabolites were down-regulated comparing obese to lean group while 459 metabolites were up-regulated and 166 metabolites were down-regulated comparing T2DM to obese groups. Several metabolites were identified as IR potential biomarkers, including amino acids (Asn, Gln, and His), methionine (Met) sulfoxide, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, serotonin, L-2-amino-3-oxobutanoic acid, and 4,6-dihydroxyquinoline. T2DM was associated with dysregulation of 42 metabolites, including amino acids, amino acids metabolites, and dipeptides. In conclusion, these pilot data have identified IR and T2DM metabolomics panels as potential novel biomarkers of IR and identified metabolites associated with T2DM, with possible diagnostic and therapeutic applications. Further studies to confirm these associations in prospective cohorts are warranted.

Keywords: chemical isotope labeling liquid chromatography; clinical metabolic panel; insulin resistance; obesity; type 2 diabetes mellitus; untargeted metabolomics profiling.