Association of brown-fat-secreted adipokine neuregulin 4 with gestational diabetes mellitus: A systematic review and meta-analysis

Abstract

Aim

Neuregulin-4, a newly identified adipokine, is thought to play a role in the regulation of energy balance and glycolipid metabolism. This meta-analysis aimed to investigate the association between Neuregulin-4 (Nrg4) and gestational diabetes mellitus (GDM).

Methods

A comprehensive search was conducted across four electronic databases- PubMed (Medline), Scopus, Europe PMC, and Google Scholar to identify relevant studies published up until August 2, 2024. A random effects model was utilized to compute the standardized mean difference (SMD) and 95 % confidence interval (CI). Statistical heterogeneity was assessed using Cochran's Q test, the I² statistic, and prediction intervals (PI). Additionally, a meta-correlation analysis was performed to explore the relationship between Nrg4 and various biochemical parameters.

Results

This meta-analysis incorporated seven studies comprising 347 subjects with GDM and 362 subjects without GDM. No significant difference was observed in circulating Nrg4 levels between the GDM and non-GDM groups (SMD = −0.35, 95 % CI = −1.17 to 0.48, p = 0.41, I² = 96 %). The 95 % prediction interval ranged from −3.35 to 2.66. Sensitivity analysis and subgroup analysis by sample size, continent, and study design reported significantly reduced levels of Nrg4 in GDM compared to non-GDM. The meta-correlation analysis revealed that Nrg4 was not significantly correlated with most biochemical and metabolic parameters studied in GDM. However, sensitivity analyses in certain instances suggested potential associations after the exclusion of specific studies.

Conclusion

Sensitivity analysis and subgroup analysis by sample size, continent, and study design reported significantly reduced levels of Nrg4 in GDM compared to non-GDM, suggesting a possible protective function of Nrg4 in GDM.