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

Abstract

<p><strong>Background: </strong>Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21) and pigment epithelium-derived factor (PEDF) are three diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. Here, we evaluated and compared their prospective associations with the development of sight-threatening diabetic retinopathy (STDR), another important diabetic micro-vascular complication.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Among these 4760 participants (mean diabetes duration of 11 years and ≥50% with non-proliferative diabetic retinopathy 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<0.001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (HR 1.28, 95%CI 1.05-1.55, p=0.013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria and baseline diabetic retinopathy status significantly improved the c-statistics (p<0.001), net reclassification index (p=0.0027) and integrated discrimination index (p=0.033) in predicting incident STDR among participants without DR or with mild DR at baseline.</p><p><strong>Conclusion: </strong>Among the three diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.</p>