Abstract

Type 2 diabetes mellitus (T2DM) intricately involves disrupted lipid metabolism. Exosomes emerge as carriers of biomarkers for early diagnosis and monitoring. This study aims to identify lipid metabolites in serum exosomes for T2DM diagnosis. Serum samples were collected from newly diagnosed T2DM patients and age and body mass index-matched healthy controls. Exosomes were isolated using exosome isolation reagent, and untargeted/targeted liquid chromatography-tandemmass spectrometry (LC-MS/MS) was used to identify and validate altered lipid metabolites. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of candidate lipid metabolites. Serum exosomes were successfully isolated from both groups, with untargeted LC-MS/MS revealing distinct lipid metabolite alterations. Notably, phosphatidylethanolamine (PE) (22:2(13Z,16Z)/14:0) showed stable elevation in T2DM-serum exosomes. Targeted LC-MS/MSconfirmed significant increase of PE (22:2(13Z,16Z)/14:0) in T2DM exosomes but not in serum. PE (22:2(13Z,16Z)/14:0) levels not only positively correlated with hemoglobin A1C levels and blood glucose levels, but also effectively distinguished T2DM patients from healthy individuals (area under the curve = 0.9141). Our research sheds light on the importance of serum exosome lipid metabolites in diagnosing T2DM, providing valuable insights into the complex lipid metabolism of diabetes.

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