Novel Visceral Obesity Indicators and Associated Metabolic Fingerprint in Incident Diabetic Retinopathy

Evidence on the association between visceral obesity and diabetic retinopathy (DR) remains sparse and debatable. We aimed to use three novel indicators, body roundness index (BRI), lipid accumulation product (LAP), and visceral adiposity index (VAI), to investigate the longitudinal relationship between visceral obesity and DR, and explore the potential metabolic mechanisms. In this prospective study based on the UK Biobank (UKB), 14,738 individuals with diabetes free of DR at baseline were included. Cox proportional hazards regression models were adopted to explore the association among the three indices and DR. Based on nuclear magnetic resonance (NMR) metabolomics of 168 plasma metabolites, we performed elastic net regression to select metabolites associated with visceral obesity and DR. Enrichment and pathway analyses were used to investigate biological pathways and network analysis was performed to discover the metabolic interactions. Over a 10-year follow-up, 1594 subjects developed DR. In the fully adjusted models, the three indices were significantly correlated with a high risk of DR, especially in Caucasians. Furthermore, we identified a metabolic fingerprint comprising 12 biomarkers associated with visceral obesity and DR, including 3-hydroxybutyrate, acetone, alanine, albumin, citrate, intermediate-density lipoprotein particles, creatinine, glucose, glycine, glycoprotein acetyls, pyruvate, and tyrosine. These metabolites were mainly enriched in alanine metabolism and their interaction was partly through succinic acid. Visceral obesity indices (BRI, LAP, and VAI) were positively associated with DR onset in patients with DM, and the potential mechanism involves alanine and energy metabolism. Our findings may promote early detection and precision prevention of DR.