The U-shaped relationship between fibroblast growth factor 21 and microvascular complication in type 2 diabetes mellitus

Abstract

Aims: The aim of this study was to investigate the relationship between serum FGF21 level and all microvascular complication including cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Methods: A total 227 T2DM patients were enrolled and serum FGF21 levels were assessed. Diabetic retinopathy, nephropathy, peripheral neuropathy (DPN), and CAN were evaluated. Results: The prevalence of retinopathy and nephropathy among the FGF21 tertiles was significantly different (p = 0.001, p = 0.006, respectively), whereas no difference was found in the prevalence of DPN and CAN. In multivariate analysis, the odds ratio (OR) for the presence of retinopathy was 0.08 for the FGF21 second tertile when compared with the first tertile (p = 0.029). OR of retinopathy in third tertile group was lower than first tertile and higher than second tertile, but statistically insignificant. Crude OR for nephropathy was 0.34 for the second FGF21 tertile, when compared with the first tertile (p = 0.015). However, FGF21 level was not significantly associated with nephropathy after multivariable adjustment. Conclusions: In the present study, there was no association between diabetic nephropathy, DPN, and CAN and serum FGF21 levels. However, we found a U-shaped relationship between both lower and higher serum FGF21 levels and diabetic retinopathy. This result suggests that the very low serum FGF21 level itself may associate with diabetic retinopathy and also relatively elevated serum FGF21 level may be a compensatory increase to protect against microvascular injury. (C) 2017 Elsevier Inc. All rights reserved.