Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy

Abstract

Context: Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium–derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. Objective: Here, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication. Methods: Baseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese individuals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis. Results: Among these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P < .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28; 95% CI, 1.05-1.55; P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P < .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline. Conclusion: Among the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.