He Yingcheng, Zhou Jingxin, Wang Jiawei, Huang Shenyu, Li Huimin, Cao Jing, Ye Juan
Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology. Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, People's Republic of China.
Invest Ophthalmol Vis Sci. 2025 Sep 2;66(12):17. doi: 10.1167/iovs.66.12.17.
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.
关于内脏肥胖与糖尿病视网膜病变（DR）之间关联的证据仍然稀少且存在争议。我们旨在使用三个新指标，即身体圆润度指数（BRI）、脂质蓄积产物（LAP）和内脏脂肪指数（VAI），来研究内脏肥胖与DR之间的纵向关系，并探索潜在的代谢机制。
在这项基于英国生物银行（UKB）的前瞻性研究中，纳入了14738名基线时无DR的糖尿病患者。采用Cox比例风险回归模型来探讨这三个指标与DR之间的关联。基于168种血浆代谢物的核磁共振（NMR）代谢组学，我们进行弹性网络回归以选择与内脏肥胖和DR相关的代谢物。使用富集和通路分析来研究生物学通路，并进行网络分析以发现代谢相互作用。
在10年的随访中，1594名受试者发生了DR。在完全调整模型中，这三个指标与DR的高风险显著相关，尤其是在白种人中。此外，我们确定了一个由12种与内脏肥胖和DR相关的生物标志物组成的代谢指纹，包括3-羟基丁酸、丙酮、丙氨酸、白蛋白、柠檬酸盐、中密度脂蛋白颗粒、肌酐、葡萄糖、甘氨酸、糖蛋白乙酰化物、丙酮酸和酪氨酸。这些代谢物主要富集在丙氨酸代谢中，它们的相互作用部分通过琥珀酸。
内脏肥胖指标（BRI、LAP和VAI）与糖尿病患者DR的发病呈正相关，潜在机制涉及丙氨酸和能量代谢。我们的发现可能会促进DR的早期检测和精准预防。
