Integrated Biomarker Profiling Of The Metabolome Associated With Impaired Fasting Glucose And Type 2 Diabetes Mellitus In Large-Scale Chinese Patients

Background: In view of a lack of consensus regarding the biomarkers of pre-diabetes and type 2 diabetes mellitus (T2DM), we sought to develop integrated biomarker profiling (IBP) of the metabolome. Methods: We studied 1,705 subjects including normal glucose tolerance, impaired fasting glucose (IFG), T2DM, and hyperlipidemia at five clinical centers in China. We aimed to construct the IBPs of IFG and T2DM, designed discovery, test, and validation phases. The discovery and test phases were employed to identify the potential serum biomarkers for IFG and T2DM. In the validation phase, the potential biomarkers were screened using Gini impurity to construct the IBP of IFG and T2DM based on the eXtreme Gradient Boosting (XGBoost) model, and individuals with hyperlipidemia were set as an interference group to evaluate the diagnostic accuracy of the IBP. Findings: Forty-one potential biomarkers were identified, in which 16 potential biomarkers were quantitatively analyzed. The IBP, which holistically reflected a mutually correlated bio-network, was constructed based on the XGBoost (AUC=0·823) model and Gini impurity (Top 10), and consisted of lysophosphatidylcholine (P-16:0), L-isoleucine, L-arginine, L-carnitine, L-phenylalanine, L-glutamic acid, L-lysine, L-methionine, L-leucine, and acetyl-L-carnitine. Besides, the service website ( http://pdm.lin-group.cn/) of the IBPs for IFG and T2DM was established to serve the public. Interpretation: IBP of the metabolome provides more consolidated evidence than isolated biomarkers, and might improve auxiliary diagnostic value in IFG and T2DM. Trial Registration: Chinese Clinical Trial Registry (ChiCTR1800014301). Funding Statement: This work was supported by the National Natural Science Foundation of China (grant number 81773891, 82073741), the National Great New Drugs Development Project of China (grant number 2017ZX09301-040), the National Key R&D Program of China (grant number 2020YFF01014606), and the Beijing Excellent Talent Project (grant number DFL20190702, 2018000021223TD09). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study protocols were approved by the Scientific Research Ethics Committee of Capital Medical University Affiliated Beijing Shijitan Hospital (2017-035) and registered on the Chinese Clinical Trial Registry (ChiCTR1800014301). All the participants provided their written informed consent.