Changes of circulating neuregulin 4 and its relationship with 25-hydroxy vitamin D and other diabetic vascular complications in patients with diabetic peripheral neuropathy

Abstract

Background: Neuregulin 4 (Nrg4) is a novel neurotrophic adipokine associated with the development of diabetic peripheral neuropathy (DPN), however, the pathological mechanism remains poorly understood. The purpose of our study was to investigate the association of circulating Nrg4 with DPN and 25-hydroxy vitamin D [25(OH)D], a multifunctional secosteroid hormone that regulates other neurotrophic factors and adipokines gene expression, and other diabetic vascular complications. Methods: Circulating Nrg4 levels were measured with an ELISA kit in 164 newly diagnosed type 2 diabetes mellitus (nT2DM) patients. The relationship between circulating Nrg4 and DPN and other parameters was analyzed. Results: Circulating Nrg4 levels were significantly lower in nT2DM patients with DPN than those without, and subjects in the highest quartile of circulating Nrg4 had significantly lower vibration perception threshold (VPT), the prevalence of DPN, the proportion of persons with VPT > 25 V, and significantly higher circulating 25(OH)D (all P < 0.01). Moreover, circulating Nrg4 was positively and independently associated with 25(OH)D, and was negatively with VPT (P < 0.01 or P < 0.05), but showed no associations with the prevalence of peripheral arterial disease, diabetic nephropathy, and diabetic retinopathy (all P > 0.05). Additionally,the prevalence of DPN and risk of DPN development were progressively decreased with increasing circulating Nrg4 quartiles, independently of potential confounding factors. Conclusions: These data demonstrate that decreased levels of circulating Nrg4 might lead to the development of DPN through its close interaction with circulating 25(OH)D not with other diabetic vascular complications. Further prospective studies are needed to identify our findings in these populations.

Diagnostic Value of the Combined Measurement of Serum HCY and NRG4 in Type 2 Diabetes Mellitus with Early Complicating Diabetic Nephropathy

“…Some studies have found that the level of circulating NRG4 in patients with metabolic syndrome is lower than that in the healthy control group, and the concentration of NRG4 is negatively correlated with the risk of developing metabolic syndrome, and NRG4 concentration may be a protective factor [ 33 ]. However, studies have found no correlation between the circulating NRG4 level and the prevalence of diabetic nephropathy and diabetic retinopathy [ 34 ]. In our study, through the analysis of large sample data, it was found that NRG4 was closely related to the incidence of HCY and DN, and the combination of NRG and HCY had excellent predictive efficacy in predicting early DN of T2DM.…”

Vitamina D e neuropatia periférica diabética - uma revisão integrativa

“…A prevalência da NPD varia entre 50-70% em pacientes com diabetes de longa duração, chegando a 8% em pacientes recémdiagnosticados 3,9,11,13-,15,18-23,25,30 . Aproximadamente 20% dos pacientes diabéticos desenvolverão neuropatia clinicamente significativa dentro de 10 anos após o início do diabetes, e esta proporção pode aumentar para 50% após 10 ou 15 anos 23,27 .…”

The journey towards physiology and pathology: Tracing the path of neuregulin 4

“… 68 Moreover, circulating levels of Nrg4 are negatively associated with the severity of type 2 diabetic peripheral neuropathy. 69 , 70 However, a human study exhibits an opposite conclusion. In this study, it was found that serum NRG4 level was negatively correlated with insulin sensitivity and positively associated with the level of high-sensitivity C relative protein (hsCRP).…”