Integrated biomarker profiling of the metabolome associated with impaired fasting glucose and type 2 diabetes mellitus in large‐scale Chinese patients

Abstract

Type 2 diabetes mellitus (T2DM) is an important cause of diabetes complications and mortality. 1 The prevalence of prediabetes including impaired fasting glucose (IFG) is approximately one-third of the population in China, 2 but comprehensive early risk evaluation is weak. Thus, it is important to identify diagnostic biomarkers of prediabetes and T2DM and improve the disease risk prediction ability. We created the validated integrated biomarker profiling (IBP) related to the development of IFG and T2DM. Moreover , the established service website of the IBP implied potential clinical application. To construct the IBPs of IFG (fasting blood glucose (FBG), 6.1 ≤ FBG < 7.0 mmol/L) and T2DM (FBG ≥ 7.0 mmol/L), 1705 participants (BMI < 30) from five centers in China recruited randomly assigned into the discovery (n = 153), test (n = 420), and validation phases (n = 1132, 146 hyperlipidemia patients as an interference group, training set of 792 [69.96%], test set of 340 [30.04%]) (Figures 1A and B), which were homogeneous (Table 1). The nontargeted metabolomics analysis was performed in the discovery and test phases to identify potential biomarkers of IFG and T2DM; in the validation phase, the potential biomarkers were quantified based on targeted metabolomics. In the discovery, after peak pretreat-ment using the 80% rule (Figures S1A-S1G in Supporting Information), 3 the quality control samples clustered together (Figures S2A-S2B), which indicated that the analysis was stable and reliable. Furthermore, there were significant differences in metabolites among the normal glucose tolerance (NGT), IFG, and T2DM groups (Figures S2A-S2F) with not overfitting (Figure S1H). After screening and identification, 31 and 42 biomarker candidates were identified in the fasted serum of IFG and T2DM patients, respectively (Tables S1-S2 in Supporting Information). In the test phase, P < .05 was regarded as significant within similar retention time ranges. Basis on the results of logistic regression (LR) and receiver operating characteristic This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.