UPLC-MS/MS-based targeted analysis of human serum revealed that aberrant arachidonic acid metabolism may contribute to the pathogenesis of type 2 diabetes mellitus.

The aberrant arachidonic acid (ARA) metabolism may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM), and some metabolites from ARA may have benefits for the differential diagnosis of T2DM. Thus, the aim of this study was to develop an ultra-high performance liquid phase coupled with mass spectrometry (UPLC-MS/MS) for determination of ARA and its 11 metabolites in the serum of patients with T2DM and explore the relation between ARA metabolites and T2DM pathogenesis. A cohort of 66 healthy individuals and 141 patients with T2DM enrolled from Suining People's Hospital Affiliated to Xuzhou Medical University was studied. The UPLC-MS/MS technique was developed and applied to obtain the serum ARA and its 11 metabolite profiles. Multivariate statistical analysis referring to metabolomics were applied for the metabolites data analysis and the differential metabolites screening. The results showed that a total number of 6 differential metabolites were presented between T2DM patients and healthy control subjects. Among these differential metabolites, (±)14(15)-epoxyeicosatrienoic acid (EET) presented the 1.64-fold elevation in T2DM patients versus healthy control subjects, significant correlation with biochemical index [fasting blood glucose (FBG) and glycated hemoglobin (HbA1c)] (P < 0.01), and Receiver Operating Characteristic (ROC) area under the curve (AUC) of 0.6063 with the sensitivity of 26.95% and specificity of 93.94% (95% confidence interval, 0.5280-0.6846) for the diagnosis of T2DM. This study advances previous findings by establishing eicosatetraenoic acids flux imbalance as a hallmark of early T2DM pathogenesis, while providing an analytical blueprint for clinical translation of lipid mediator biomarkers in type 2 diabetic patients.