Circulating inflammatory cytokines and gestational diabetes mellitus: Unraveling the role of macrophage migration inhibitory factor (MIF) through a bidirectional mendelian randomization study

Background: Several studies have identified associations between some of circulating inflammatory cytokines and gestational diabetes mellitus (GDM). However, the causal role of these associations remains unclear and unsystematic. We aimed to provide evidence for the causal relationships between circulating inflammatory cytokines and gestational diabetes mellitus. Methods: We performed bidirectional two-sample Mendelian randomization (2SMR) to investigate the causal connection between circulating inflammatory cytokines and gestational diabetes mellitus. Publicly accessible data for circulating inflammatory cytokines (8,293 individuals) and gestational diabetes mellitus (123,579 individuals) were obtained from genome-wide association study (GWAS). Results: Only one causal association was identified between circulating inflammatory cytokines and GDM. The inverse variance weighting (IVW) method showed that macrophage migration inhibitory factor (MIF) increased the risk of GDM (OR 1.162, 95%CI 1.044,1.293). Moreover, two causal associations were detected between GDM and circulating inflammatory cytokines. GDM was negatively correlated with interferon gamma-induced protein 10 (IP10) (Beta-0.129, 95%CI-0.236,-0.231) and interleukin-18 (IL18) (Beta-0.133, 95%CI-0.241,-0.026). Conclusion: Mendelian randomization study revealed MIF as a risk factor for gestational diabetes mellitus. This finding offers a new and valuable insight into the pathophysiological mechanisms underlying GDM.