Leucine-rich α-2-glycoprotein predicts proliferative diabetic retinopathy in type 2 diabetes

We aim to examine the association of plasma leucine-rich-α-2-glycoprotein 1 (LRG1) with diabetic retinopathy (DR) in type 2 diabetes. At baseline visit, plasma LRG1 levels were assessed using ELISA. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV). At follow-up visit (median = 3.2 years), digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). DR was diagnosed in 396 (32.8%) of 1206 patients. DR has higher LRG1 than non-DR (19.5 ± 11.3vs.16.9 ± 8.9 μg/ml, p ≪ 0.001). After adjustment, LRG1 was not associated with DR (OR = 1.2, [95% CI, 0.96–1.30], p = 0.16). LRG1 was higher in PDR (n = 107) than NPDR (n = 270) (23.2 ± 15.4vs.18.1 ± 8.9 μg/ml, n = 270, p ≪ 0.001). After adjustment, with 1-SD increase in LRG1, the relative risk of NPDR and PDR was 0.99 ([0.83–1.18], p = 0.91) and 1.42 ([95% CI, 1.14–1.76], p = 0.002) (p-trend = 0.01), respectively. We didn't observe significant improvement in AUC after adding LRG1 into the model. Baseline PWV mediated 12.0% of the association between LRG1 and PDR (p = 0.03). Baseline plasma LRG1 is associated with PDR, suggesting it maybe a promising biomarker for prediction for advanced proliferative stages of DR. The mediation result indicates the potential benefit of ameliorating central arterial stiffness to prevent PDR.