Plasma Metabolomics Analyses of Type 2 Diabetes Patients Diagnosed with Retinopathy

Abstract

Background: Diabetic retinopathy (DR) is an extremely debilitating microvascular complication of diabetes mellitus (DM), and changes in the internal physiological microenvironment can shape the progression of this disease. At present, few metabonomics studies have systematically studied the small and medium molecular metabolite changes during DR progression. Methods: Peripheral blood samples from 91 patients with DR (41 patients with proliferative diabetic retinopathy (PDR) and 50 patients with non-proliferative diabetic retinopathy (NPDR)), 91 gender- and age-matched non-DR type 2 diabetes mellitus (T2DM) patients, and 91 healthy controls were analyzed by gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). First, univariate and multivariate statistical analyses were used to identify metabolites with significant differences. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to analyze the significantly affected metabolic pathways among the groups, and Spearman correlation analyses were used to study the correlation between these different metabolites and clinical parameters. Finally, candidate biomarkers related to the progression of T2DM and DR were selected by K-means and logistic regression analyses. Results: The metabolism of amino acids, glucose, and phosphatidylinositol was revealed to be significantly abnormal in T2DM and DR patients (NPDR and PDR). While potential diagnostic markers of T2DM and PDR were identified, further validation is needed to elucidate how these differential metabolites and related metabolic pathways influence disease progression. Conclusions: In this study, a metabolomics approach was utilized in an effort to detect specific biomarkers of T2DM in patients with or without DR while exploring the potentially pathogenic roles that these metabolites may play in DR progression.