Background: Diabetic macular edema (DME), a sight-threatening retinopathy, is a leading cause of vision loss in persons with diabetes mellitus. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop DME, suggesting the existence of other potential pathogenic factors underlying DME. This study aimed to investigate the plasma metabotype of patients with DME and to identify novel metabolite markers for DME. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of DME.

Methods: To match clinical parameters between case and control subjects, patients with DME (DME, n=30) or those with diabetes but without DME (Control, n=30) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS).

Results: A total of 188 distinct metabolites between DME and Control groups were identified (VIP > 1, Fold Change > 1.5 or < 0.5, and P < 0.05). These metabolites mainly included Lipids and lipid-like molecules (71%), organic acids and derivatives (17%), Organic oxygen compounds (8%) and others. The distinct metabolites between DME and Control groups were enriched in 5 KEGG pathways, namely, lysine degradation, arachidonic acid metabolism, riboflavin metabolism, sulfur relay system, and thyroid hormone synthesis. Finally, 4 metabolites were selected as candidate biomarkers for DME, namely, Violaxanthin, uridine, D-Glucopyranuronic acid, and Capryloylglycine. The area under the curve for these biomarkers were 0.89, 0.85, 0.86, and 0.82, respectively.

Conclusions: This study suggested that impairment in the metabolism and 4 potential metabolites were identified as metabolic dysregulation associated with DME, which might provide insights into potential new pathogenic pathways for DME.


X. Zhu: None.


National Key Research and Development Program of China (2017YFC0909600)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at