Lipidomic analysis of serum exosomes identifies a novel diagnostic marker for type 2 diabetes mellitus.

Ling Zhang, Ting Lu, Baocheng Zhou, Yaoxiang Sun, Liyun Wang, Guohong Qiao, Tingting Yang
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Abstract

Background: 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.

Methods: 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-tandem mass 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.

Results: 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/MS confirmed 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).

Conclusion: 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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血清外泌体的脂质体分析发现了一种新型的 2 型糖尿病诊断标记物。
背景:2 型糖尿病(T2DM)与脂质代谢紊乱密切相关。外泌体是早期诊断和监测的生物标志物载体。本研究旨在鉴定血清外泌体中的脂质代谢物,以用于 T2DM 诊断:方法:收集新诊断出的 T2DM 患者和年龄与体重指数相匹配的健康对照者的血清样本。使用外泌体分离试剂分离外泌体,并使用非靶向/靶向液相色谱-串联质谱法(LC-MS/MS)鉴定和验证改变的脂质代谢物。采用接收者操作特征曲线分析评估候选脂质代谢物的诊断价值:结果:成功从两组患者中分离出血清外泌体,非靶向 LC-MS/MS 发现了不同的脂质代谢物变化。值得注意的是,磷脂酰乙醇胺(PE)(22:2(13Z,16Z)/14:0)在T2DM血清外泌体中显示出稳定的升高。LC-MS/MS靶向检测证实,T2DM外泌体中的磷脂酰乙醇胺(22:2(13Z,16Z)/14:0)显著增加,而血清中则没有增加。PE(22:2(13Z,16Z)/14:0)水平不仅与血红蛋白 A1C 水平和血糖水平呈正相关,还能有效区分 T2DM 患者和健康人(曲线下面积 = 0.9141):我们的研究揭示了血清外泌体脂质代谢物在诊断 T2DM 中的重要性,为了解糖尿病复杂的脂质代谢提供了宝贵的信息。
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