High-Coverage Serum Metabolomics Reveals Metabolic Pathway Dysregulation in Diabetic Retinopathy: A Propensity Score-Matched Study

Chengnan Guo; Depeng Jiang; Yixi Xu; Fang Peng; Shuzhen Zhao; Huihui Li; Dongzhen Jin; Xin Xu; Zhezheng Xia; Mingzhu Che; Mengyuan Lai; Ruogu Huang; Hui Wang; Chao Zheng; Guangyun Mao

doi:10.3389/fmolb.2022.822647

High-Coverage Serum Metabolomics Reveals Metabolic Pathway Dysregulation in Diabetic Retinopathy: A Propensity Score-Matched Study

Front Mol Biosci. 2022 Mar 17:9:822647. doi: 10.3389/fmolb.2022.822647. eCollection 2022.

Authors

Chengnan Guo^{1

2}, Depeng Jiang³, Yixi Xu^{1

2}, Fang Peng^{1

2}, Shuzhen Zhao^{1

2}, Huihui Li^{1

2}, Dongzhen Jin^{1

2}, Xin Xu⁴, Zhezheng Xia^{1

2}, Mingzhu Che^{1

2}, Mengyuan Lai^{1

2}, Ruogu Huang^{1

2}, Hui Wang^{1

2}, Chao Zheng⁵, Guangyun Mao^{1

2

6}

Affiliations

¹ Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
² Center on Evidence-Based Medicine and Clinical Epidemiological Research, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
³ Department of Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁴ Department of Nursing, School of Nursing, Wenzhou Medical University, Wenzhou, China.
⁵ The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁶ Center on Clinical Research, The Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Background: Diabetic retinopathy (DR) is a major diabetes-related disease linked to metabolism. However, the cognition of metabolic pathway alterations in DR remains scarce. We aimed to corroborate alterations of metabolic pathways identified in prior studies and investigate novel metabolic dysregulations that may lead to new prevention and treatment strategies for DR. Methods: In this case-control study, we tested 613 serum metabolites in 69 pairs of type 2 diabetic patients (T2DM) with DR and propensity score-matched T2DM without DR via ultra-performance liquid chromatography-tandem mass spectrometry system. Metabolic pathway dysregulation in DR was thoroughly investigated by metabolic pathway analysis, chemical similarity enrichment analysis (ChemRICH), and integrated pathway analysis. The associations of ChemRICH-screened key metabolites with DR were further estimated with restricted cubic spline analyses. Results: A total of 89 differentially expressed metabolites were identified by paired univariate analysis and partial least squares discriminant analysis. We corroborated biosynthesis of unsaturated fatty acids, glycine, serine and threonine metabolism, glutamate and cysteine-related pathways, and nucleotide-related pathways were significantly perturbed in DR, which were identified in prior studies. We also found some novel metabolic alterations associated with DR, including the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives in DR. Conclusions: The results suggest that the metabolism disorder in DR can be better understood through integrating multiple biological knowledge databases. The progression of DR is associated with the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives.

Keywords: diabetic retinopathy; integrated pathway analysis; metabolic pathway dysregulation; metabolomics study; propensity score matching.