Pre-diagnostic biomarkers of type 2 diabetes identified in the UAE's obese national population using targeted metabolomics

Abstract

Currently, type 2 diabetes mellitus (T2DM) and obesity are major global public health issues, and their prevalence in the United Arab Emirates (UAE) are among the highest in the world. In 2019, The UAE diabetes national prevalence was 15.4%. In recent years there has been a considerable investigation of predictive biomarkers associated with these conditions. This study analysed fasting (8 h) blood samples from an obese, normoglycemic cohort and an obese, T2DM cohort of UAE nationals, employing clinical chemistry analysis, 1D 1 H NMR and mass spectroscopy (FIA-MS/ MS and LC-MS/MS) techniques. The novel fndings reported for the frst time in a UAE population revealed signifcant diferences in a number of metabolites in the T2DM cohort. Metabolic fngerprints identifed by NMR included BCAAs, trimethylamine N-oxide, β-hydroxybutyrate, trimethyl uric acid, and alanine. A targeted MS approach showed signifcant diferences in lysophosphatidylcholines, phosphatidylcholines, acylcarnitine, amino acids and sphingomyelins; Lyso.PC.a.C18.0, PC.ae.C34.2, C3.DC..C4.OH, glutamine and SM.C16.1, being the most signifcant metabolites. Pearson’s correlation studies showed associations between these metabolites and the clinical chemistry parameters across both cohorts. This report identifed diferences in metabolites in response to T2DM in agreement with many published population studies. This contributes to the global search for a bank of metabolite biomarkers that can predict the advent of T2DM and give insight to its pathogenic mechanisms