AUTHOR=Wang Xinyu , Yang Shu , Yang Guangyan , Lin Jialong , Zhao Pengfei , Ding Jingyun , Sun Hongyan , Meng Ting , Yang Ming Ming , Kang Lin , Liang Zhen 

TITLE=Novel risk score model for non-proliferative diabetic retinopathy based on untargeted metabolomics of venous blood

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1180415

DOI=10.3389/fendo.2023.1180415

ISSN=1664-2392

ABSTRACT=Background and Purpose: Nonproliferative diabetic retinopathy (NPDR) occurs in the early stages of Diabetic retinopathy (DR), and the study of its metabolic markers will help to prevent DR. Hence, we aimed to establish a risk score based on multiple metabolites through untargeted metabolomic analysis of venous blood from NPDR patients and diabetic non-DR patients.
Experimental Approach: Untargeted metabolomics of venous blood samples from patients with NPDR, diabetes melitus without DR were performed using high-performance liquid chromatography-mass spectrometry.
Results: Detailed metabolomic evaluation showed distinct clusters of metabolites in plasma samples from patients with NPDR and diabetic non-DR patients. NPDR patients had significantly higher levels of phenylacetylglycine, L-aspartic acid, tiglylglycine, and 3-sulfinato-L-alaninate, and lower level of indolelactic acid, threonic acid, L-arginine (Arg), and 4-dodecylbenzenesulfonic acid compared to control. The expression profiles of these eight NPDR risk-related characteristic metabolites were analyzed using Cox regression to establish a risk score model. Subsequently, univariate and multivariate Cox regression analyses were used to determine that this risk score model was a predictor of independent prognosis for NPDR. 
Conclusions: Untargeted metabolome analysis of blood metabolites revealed unreported metabolic alterations in NPDR patients compared with those in diabetic non-DR patients or MH. In the venous blood, we identified depleted metabolites thA and Arg, indicating that they might play a role in NPDR development.