Metabolic Biomarkers for Prognostic Prediction of Pre-diabetes: results from a longitudinal cohort study

To investigate the metabolic biomarkers of predicting the transition from pre-diabetes (pre-DM) to normal glucose regulation (NGR) and diabetes (DM) in a longitudinal cohort study. 108 participants with pre-DM were followed up for ten years and divided into 3 groups according to different glycemic outcomes. 20 participants progressed to DM, 20 regressed to NGR, and 68 remained at pre-DM. Alterations in plasma metabolites in these groups were evaluated by untargeted ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Twenty three metabolites related to glycerophospholipid metabolism, oxidation and antioxidation were associated with the process from pre-DM to NGR, while twenty two metabolites related to amino acid metabolism, glycerophospholipid metabolism and mitochondrial β-oxidation played important roles in the progression to DM. Results from stepwise logistic regression analysis showed that five biomarkers (20-Hydroxy-leukotriene E4, Lysopc(20:4), 5-methoxytryptamine, Endomorphin-1, Lysopc(20:3)) were good prediction for the restoration to NGR, and five biomarkers (Iso-valeraldehyde, linoleic acid, Lysopc(18:1), 2-Pyrroloylglycine, Dityrosine) for the development of DM. The findings suggest that the combination of these potential metabolites may be used for the prognosis of pre-DM. Targeting the pathways that involved in these prognostic biomarkers would be beneficial for the regression to NGR and the early prevention of DM among pre-DM.