ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
UHPLC-MS/MS-based plasma untargeted lipidomic analysis in patients with diabetes mellitus combined with hyperuricemia
Provisionally accepted
- 1The Affiliated Fuzhou Center for Disease Control and Prevention of Fujian Medical University, Fuzhou, China
- 2Fujian Medical University, Fuzhou, China
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Objective: To compare lipid metabolites among patients with diabetes mellitus and hyperuricemia (DH), diabetes mellitus (DM) alone, and healthy controls, and to identify perturbed lipid metabolic pathways in DH. Methods: In a cross-sectional study in Fuzhou, Fujian Province, China (June 2019–July 2020), we enrolled 17 DH and 17 DM patients and 17 age- and sex-matched healthy controls aged 18 years and older. Fasting blood samples were collected. Untargeted lipidomics was performed using ultra-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Differential lipids were screened using t-tests with fold change; multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) assessed group separation. Pathway analysis was conducted with MetaboAnalyst 5.0. Results: We detected 1361 lipid species across 30 subclasses. Multivariate analyses revealed clear separation among DH, DM, and NGT groups, indicating distinct lipidomic profiles. DH vs NGT identified 31 significantly altered lipid metabolites. Among the most pronounced changes, 13 triglycerides (TGs) including TG(16:0/18:1/18:2), 10 phosphatidylethanolamines (PEs) such as PE(18:0/20:4), and 7 phosphatidylcholines (PCs) including PC(36:1) were upregulated, while one phosphatidylinositol (PI) was downregulated. Pathway enrichment indicated involvement of six major lipid pathways, with glycerophospholipid metabolism (impact = 0.199) and glycerolipid metabolism (impact = 0.014) as the most perturbed in DH. In the DH vs DM comparison, 12 differential lipids were identified, largely mapping to the same core pathways, underscoring their role in the pathophysiology of diabetes with hyperuricemia. Conclusions: DH exhibits a markedly altered lipidome relative to DM and healthy controls. Thirty-one lipids differed significantly, and perturbations in glycerophospholipid and glycerolipid metabolism appear central to the metabolic derangements accompanying diabetes when complicated by hyperuricemia.
Keywords: Diabetes Mellitus, Hyperuricemia, Lipid Metabolism, lipidomics, Triglycerides, Phosphatidylethanolamine
Received: 30 Jun 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Xu, Zhu, Chen, Zhang, Fang, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Youqiong Xu, joancoco@126.com
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