Metabolic alterations in diabetic patients: aqueous humor profiling for biomarker discovery

Diabetic retinopathy, a leading cause of vision loss in working-age populations, is a severe complication of diabetes mellitus. Metabolomics, a key approach in systems biology, offers insights into the complex pathophysiology of diabetes by analyzing low-molecular-weight compounds in biological contexts. This study investigated metabolite alterations in the aqueous humor of diabetic and non-diabetic patients undergoing cataract surgery to identify potential biomarkers associated with diabetes. Aqueous humor samples from 191 patients (48 diabetic, 143 non-diabetic) were analyzed using targeted liquid chromatography-mass spectrometry. Metabolite data were normalized and statistically evaluated using univariate analysis, including fold change calculations, t-tests, and volcano plots. Pathway enrichment analysis was performed using KEGG, SMPDB, and RaMP-DP databases. Key findings revealed differential abundance of several metabolites, including upregulated 3-hydroxykynurenine, histamine, and octanoylcarnitine, and downregulated putrescine in diabetic patients. Although some metabolites exhibited low p-values (< 0.05), high FDR limited the statistical robustness of these findings. Quantitative enrichment analysis suggested potential involvement of the kynurenine pathway and tryptophan catabolism in diabetes-related metabolic changes. The study highlights the potential roles of these metabolites in diabetes-related ocular changes, supported by prior research linking them to oxidative stress, inflammation, and metabolic dysregulation. Antioxidative therapies targeting diabetes-associated metabolic alterations may offer potential for mitigating diabetes-related complications. High FDR underscores the need for cautious interpretation and further validation in larger cohorts. Future studies should focus on longitudinal analyses and mechanistic investigations to clarify the diagnostic and prognostic potential of these metabolites in diabetic retinopathy and other diabetes-related complications.