Metabolomics Based Mediating Role of Non-lipid Metabolites in the Relationship between Obesity and Diabetic Retinopathy: a Mendelian Randomization Study
摘要
Background Obesity can influence the occurrence and progression of diabetic retinopathy (DR) through various pathways, however there are limited studies on the mediation of DR by obesity through non-lipid metabolic pathways. Objective To investigate the mediating role of non-lipid metabolites in the relationship between obesity and DR. Methods In August 2023, we utilized genome-wide association study (GWAS) data and conducted Mendelian randomization (MR) analysis to explore the mediating role of non-lipid metabolites in the association between obesity and DR. Results BMI (OR=1.78, P=5.3E-12) and waist-to-hip ratio (WHR) (OR=1.91, P=1.3E-10) was associated with increased risk of DR, respectively. Lower levels of isoleucine (OR=0.62, P=0.039) , pyruvate (OR=0.60, P=0.039) , albumin (OR=0.65, P=0.002) , glycoprotein (OR=0.92, P=0.002) , and decreased ratio of dienes to double bonds (OR=0.93, P=0.048) was associated with increased risk of DR, respectively. Positive causal associations were observed between BMI and isoleucine (OR=1.21, P=1.0E-08) , glycoprotein (OR=1.33, P=3.2E-14) , pyruvate (OR=1.08, P=0.03) , and negative causal associations with albumin (OR=0.93, P=0.04) and the ratio of dienes to double bonds (OR=0.82, P=2.8E-05) . Positive causal associations were also found between WHR and isoleucine (OR=1.34, P=3.4E-08) and glycoprotein (OR=1.26, P=1.2E-04) . Isoleucine (β=-0.16, P=0.019) , glycoprotein (β=-0.05, P=0.029) , pyruvate (β=-0.07, P=0.027) , and the ratio of dienes to double bonds (β=0.02, P=0.036) mediated the causal association between BMI and DR, while isoleucine (β=-0.21, P=7.2E-04) and glycoprotein (β=-0.03, P=0.031) mediated the causal association between WHR and DR. Conclusion Obesity has a positive causal association with DR, with BMI's association with DR mediated by isoleucine, glycoprotein, pyruvate, and the ratio of dienes to double bonds, and WHR's association with DR mediated by isoleuc