Chemokines in Gestational Diabetes Mellitus

Abstract

BackgroundStudies investigating chemokines in gestational diabetes mellitus (GDM) have yielded mixed results. The purpose of this meta-analysis was to explore whether concentrations of chemokines in patients with GDM differed from that of the controls.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched Web of Science, Embase, Cochrane Library, and PubMed databases for articles, published in any language, on chemokines and GDM through August 1st, 2021. The difference in concentrations of chemokines between patients with GDM and controls was determined by a standardized mean difference (SMD) with a 95% confidence interval (CI), calculated in the meta-analysis of the eligible studies using a random-effects model with restricted maximum-likelihood estimator.ResultsSeventeen studies met the inclusion criteria for the meta-analysis. Altogether, they included nine different chemokines comparisons involving 5,158 participants (1,934 GDM patients and 3,224 controls). Results showed a significant increase of these chemokines (CCL2, CXCL1, CXCL8, CXCL9, and CXCL12) in the GDM patients compared with the controls. However, there was a significant decrease of the chemokines, CCL4, CCL11 and CXCL10, in the GDM patients compared with the controls. Moreover, subgroup analysis revealed a potential role of chemokines as biomarkers in relation to laboratory detection (different sample type and assay methods) and clinical characteristics of GDM patients (ethnicity and body mass index).ConclusionGDM is associated with several chemokines (CCL2, CCL4, CCL11, CXCL1, CXCL8, CXCL9, CXCL10 and CXCL12). Therefore, consideration of these chemokines as potential targets or biomarkers in the pathophysiology of GDM development is necessary. Notably, the information of subgroup analysis underscores the importance of exploring putative mechanisms underlying this association, in order to develop new individualized clinical and therapeutic strategies.

Identification of FGF13 as a Potential Biomarker and Target for Diagnosis of Impaired Glucose Tolerance

“…Recent studies have shown that higher CCL2 concentrations are associated with the risks of early IR and the development of obesity. In addition, CCL2 can interact with its specific receptor CCR2, playing a primary role in regulating the islet immune microenvironment and monocyte infiltration and migration [ 29 ]. Inhibition of CCL2 improves glucose disorder, significantly reduces the progression of diabetes complications, and improves the survival rate of islet transplantation in patients with T1DM [ 26 , 30 , 31 , 32 , 33 ].…”

Gestational diabetes mellitus dysregulates the PD-1/PD-L1 axis at the feto-maternal interface

“…These signaling molecules affect immune responses in the pancreas. Therefore, more research must be conducted to investigate the role of these cytokines in GDM and at the DB 11 .…”

IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies

“…The first (and, so far, the only) meta-analysis and systematic review of chemokines and their cognate receptors, suggests a role for IL-8 in the shaping of the complex immune microenvironment in GDM [ 261 ]. This is supported by case-control studies reporting increased circulating IL-8 levels in GDM patients, compared to healthy pregnancies [ 115 , 176 , 179 , 180 ].…”

“…Data suggest that persistent inflammatory stimuli may perpetuate this vicious circle of IL-8 production in human adipocytes over the p38 MAPK pathway, which is also implicated in promoting IR in human adipocytes [ 269 ]. Moreover, IL-8 in obesity may downregulate adiponectin in adipocytes [ 169 , 261 ]. A decreased adiponectin level is a common finding in IR, DM and GDM [ 270 ].…”

“…IL-6 appears to be decisively involved in the development of IR and GDM, primarily by the impaired phosphorylation of the insulin receptors and the induced expression of SOCS3, which inhibits the insulin signaling in peripheral tissues, adipocytes and hepatocytes [ 266 ]. Moreover, IL-8 seems to participate in promoting obesity, inflammation and IR, by attracting additional adipocytes and immune cells in the adipose tissue, and by interfering with insulin signaling by downregulation of adiponectin and/or activation of the p38 MAPK pathway [ 112 , 261 , 269 ]. However, studies investigating inflammatory mediators in the maternal and placental compartments in GDM are not always consistent, whereas data regarding the fetal inflammatory state in GDM are lacking.…”