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.