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 1H NMR and mass spectroscopy (FIA-MS/MS and LC-MS/MS) techniques. The novel findings reported for the first time in a UAE population revealed significant differences in a number of metabolites in the T2DM cohort. Metabolic fingerprints identified by NMR included BCAAs, trimethylamine N-oxide, β-hydroxybutyrate, trimethyl uric acid, and alanine. A targeted MS approach showed significant differences 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 significant metabolites. Pearson’s correlation studies showed associations between these metabolites and the clinical chemistry parameters across both cohorts. This report identified differences 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.

A Preliminary Study Showing the Impact of Genetic and Dietary Factors on GC–MS-Based Plasma Metabolome of Patients with and without PROX1-Genetic Predisposition to T2DM up to 5 Years Prior to Prediabetes Appearance

“…Amino acids (AAs) are crucial biological compounds that play a key metabolic and physiological role in all living organisms [66]. It was confirmed that these metabolites are useful diagnostic markers because they are considerably altered in prediabetes state and continue to increase during T2DM progression [67]. The Framingham Offspring Study has shown that elevated AAs were able to predict an increased risk of T2DM up to 12 years prior to disease onset [68].…”

Prospective analysis of circulating metabolites and endometrial cancer risk

“…The potential positive association between SM C18:0 and endometrial cancer risk is in line with a recent report of a positive association of SM C18:0 with the endometrioid subtype of ovarian cancer in a prospective cohort [ 36 ]. Associations between sphingomyelins and diabetes and insulin resistance have also been observed and may partly explain their association with endometrial cancer [ 37 , 38 ]. Alterations of sphingolipid metabolism have been previously shown in endometrial cancer tissue compared to healthy endometrium [ 39 ] as well as in plasma of endometrial cancer patients compared to controls [ 19 ].…”

Evaluation of Changes in Metabolites of Saliva in Canine Obesity Using a Targeted Metabolomic Approach

“…Finally, the two ACs found in our study were increased in the saliva of obese dogs compared to normal dogs. The ACs were positively correlated with the fat-free mass index in a previous study in humans [ 21 ]; furthermore, they were increased in obesity development and T2DM during pregnancy in women [ 30 ] and situations of obesity-related insulin resistance [ 24 ].…”

“…Salivary sphingolipids were significantly increased in the obese group compared to the control. Sphingomyelin plays a role in cell apoptosis by its hydrolysis into ceramide, which is in turn responsible for the induction of apoptosis and involvement in inflammatory processes [ 24 ]. Ceramides are involved in insulin-mediated glucose uptake and are thought to play an essential role in the development of insulin resistance [ 25 ].…”

“…Furthermore, it has been shown that different phospholipids are increased in the serum of dogs with obesity [ 29 ]. Interestingly, decreased levels of PCs and their implication for the development of obesity-related T2DM in humans have also been reported [ 24 ]. Further studies are necessary to elucidate the cause of the different responses of PCs in the saliva of obese canines.…”