Update publication. Objective: This study aimed to explore the mechanisms of early-onset T2DM by analyzing proteomic changes at different stages of glucose metabolism. Methods: A total of 40 individuals undergoing routine physical health examinations between December 2016 and April 2017 were enrolled. Subjects were divided into four groups based on fasting blood glucose (FPG) levels: 10 cases with FPG <5.6 mmol/L (group A); 10 cases with FPG ≥5.6 mmol/L and <6.1 mmol/L (group B); 10 cases with FPG ≥6.1 mmol/L and <7.0 mmol/L (group C); and 10 cases with FPG ≥7.0 mmol/L (group D). Results of differential proteomic analysis performed by label-free quantification were compared with metabolites determined by metabolomics. Results: A total of 277 differentially expressed proteins were screened and were identified as mainly secreted proteins. Comparing group A with group B, 32 proteins were up-regulated (fold change >1.2; p <0.05) and 18 proteins were down-regulated (fold change <-1.2; p <0.05). Comparing group B with group C, 3 pro