Alteration of serum neuregulin 4 and neuregulin 1 in gestational diabetes mellitus

Abstract

Context: Neuregulin 4 (Nrg4) and neuregulin 1 (Nrg1) have been shown to play vital roles in several disorders of glucose metabolism. The pathophysiological role of Nrg4 and Nrg1 in gestational diabetes mellitus (GDM), however, remains poorly understood. We assessed the clinical relevance of the two cytokines in patients with GDM. Methods: The study recruited 36 GDM patients and 38 age-matched, gestational age (24–28 weeks of gestation)–matched, and BMI (during pregnancy)–matched controls in this study. Serum Nrg4 and Nrg1 were measured using ELISA. Inflammatory factors such as IL-6, IL-1β, leptin, TNF-α, and monocyte chemotactic protein 1 (MCP-1) were determined via Luminex technique. Results: Serum Nrg4 in GDM patients was significantly lower than that in the controls, while Nrg1 was significantly higher in the GDM group ( p < 0.01). Inflammatory factors such as IL-6, leptin, and TNF-α were significantly increased in GDM patients, while MCP-1 and IL-1β were not significantly different between the two groups. In addition, serum Nrg4 was negatively correlated with fasting glucose ( r = −0.438, p = 0.008), HOMA-IR ( r = −0.364, p = 0.029), IL-6 ( r = −0.384, p = 0.021), leptin ( r = −0.393, p = 0.018), TNF-α ( r = −0.346, p = 0.039), and MCP-1 ( r = −0.342, p = 0.041), and positively correlated with high-density lipoprotein cholesterol (HDL-C) ( r = −0.357, p = 0.033) in GDM group. Serum Nrg1 was positively correlated with BMI ( r = 0.452, p = 0.006), fasting glucose ( r = 0.424, p = 0.010), HOMA-IR ( r = 0.369, p = 0.027), and triglyceride ( r = 0.439, p = 0.007). The decrease of Nrg4 and the increase of Nrg1 were significantly related to the increased prevalence of GDM. Finally, ROC curve results indicated that Nrg1 combined with IL-6 and TNF-α might be an effective means for GDM screening. Conclusions: Lower circulating Nrg4 and higher circulating Nrg1 serve risk factors of GDM. Nrg1 combined with IL-6 and TNF-α might be a potential tool for GDM screening.

The AHNAK induces increased IL-6 production in CD4+ T cells and serves as a potential diagnostic biomarker for recurrent pregnancy loss

“…IL-6 is produced by diverse cells, including monocytes, T cells, B cells, myometrial cells, and endothelial cells [ 17 ]. It has been previously shown that maternal serum IL-6 elevation during pregnancy could induce abnormal behavior in offspring in mice, and the human serum IL-6 level is significantly increased in patients with gestational diabetes mellitus [ 18 , 19 ]. However, the concentration of IL-6 is also reported to be significantly decreased in the supernatants of cultured peripheral blood mononuclear cells (PBMCs) from patients with RPL as compared to that in normal pregnant women during the first trimester [ 20 ].…”

Clinical Significance of Neuregulin 4, Afamin, and SERPINB1 in Gestational Diabetes Mellitus and Their Relationship with Insulin Resistance

“…Attique et al concluded that NRG4 concentration declined in GDM females compared to the healthy group ( P < 0.04) and showed a weak association with HOMA-IR but the significant inverse association with insulin, indicating a potential role of NRG4 in regulating insulin sensitivity, and its possibility as a biomarker of GDM [ 37 ]. During the second and third trimesters, Zhang et al indicated the females in the control group exhibited significantly higher serum NRG4 concentration than the GDM females and NRG4 concentration was negatively related to fasting glucose and HOMA-IR [ 38 ]. These findings were similar to ours, which suggested that NRG4 expression decreased in GDM patients than that in non-GDM patients, and the difference was statistically significant.…”

Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

“…Although numerous animal studies considering neuregulin-4 (NRG4) have been performed, there are limited data in humans. NRG4 is known to serve as a one of the factors improving insulin sensitivity [ 135 ], protecting the liver from fatty liver disease (FLD) [ 131 ] and its low circulating level may potentially serve as a risk factor for gestational diabetes mellitus [ 136 ]; however, the NRG4–PCOS relationship is poorly represented in the literature.…”