Untargeted and Targeted Lipidomics Unveil Dynamic Lipid Metabolism Alterations in Type 2 Diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a growing body of evidence suggesting the central role of lipid metabolism in its pathogenesis. However, the dynamic changes in lipid metabolism across different stages of T2DM remain understudied. OBJECTIVE: This study aimed to elucidate the temporal alterations in lipid metabolism in T2DM using an integrated lipidomics approach. METHOD: Serum samples from 155 subjects were analyzed using LC-MS-based lipidomics, including untargeted and targeted approaches. RESULTS: We identified significant alterations in 44 lipid metabolites in newly diagnosed T2DM patients and 29 in high-risk individuals, compared with healthy controls. Key metabolic pathways such as sphingomyelin, phosphatidylcholine, and sterol ester metabolism were disrupted, highlighting the involvement of insulin resistance and oxidative stress in T2DM progression. Moreover, 13 lipid metabolites exhibited diagnostic potential for T2DN, showing consistent trends of increase or decrease as the disease progressed. CONCLUSION: Our findings underscore the importance of lipid metabolism in T2D development and identify potential lipid biomarkers for early diagnosis and monitoring of disease progression, which contribute to paving the way for novel therapeutic strategies.