The Relationships Of Serum Levels Of Selected Inflammatory And Anti-inflammatory Cytokines With Gestational Diabetes

BackgroundGestational diabetes mellitus(GDM),a disease defined as abnormal glucose tolerance with onset or first recognition during gestation,is a pathological state that similar to type 2 diabetes mellitus(T2DM)in which pancreatic ? cells cannot release adequate insulin to meet the increased insulin demand.Currently,chronic insulin resistance is thought to be the major pathological feature of GDM,and inflammation-related factor is one of the central pathogenic mechanisms of insulin resistance,which affects the activation and transcriptional and post-transcriptional modification of several important kinase and metabolism of some lipid-related factors involved in the insulin signalling pathway.Researches have proved that inflammatory/anti-inflammatory cytokines play a significant role throughout the pregnancy and are important factors in the pathological processes of GDM.However,these results were from different researches.Up to now,systematic studies of inflammatory factors in a specific population are still lacked and the exact relationships between inflammatory factors,such as nerve growth factor(NGF),and some important metabolic indexes in Chinese GDM patients are still limited.Therefore,we conducted a 1:1 matched case-control study to explore the systematic changes of inflammatory/anti-inflammatory factors during gestation and their relationships with Chinese gestational diabetes.According to maternal age,pregestational body mass index(BMI),and gestational week,200 pairs of subjects in the second trimester and 130 pairs of subjects in the third trimester were included.Serum levels of Interleukin-6(IL-6),Interleukin-8(IL-8),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-alpha(TNF-?),Interleukin-1 beta(IL-1?),leptin,NGF and GDF15 were measured by enzyme immunoassay.We found that in the second trimester,GDM patients had lower IL-8 levels while higher NGF levels than did normal controls(P=0.015 and P<0.001,respectively),and NGF levels were not only independently and positively associated with glucose levels during the 75-g oral glucose tolerance test(OGTT),including fasting,1-h and 2-h glucose levels and the area under curve of glucose(AUCG),but also positively related to insulin sensitivity and secretion(all P<0.05).Moreover,IL-6 and leptin levels were positively correlated with insulin resistance and secretion,and TNF-? levels were independently and positively related to insulin resistance(all P<0.05).However,in the third trimester,no significant differences in levels of NGF and IL-8 were found between GDM patients and normal controls(P>0.05).Only lower leptin levels were observed in the GDM group(P=0.031),and GDF15 levels were significantly higher in the GDM patients than in the normal controls(P<0.001).In addition,GDF15 levels were independently and positively associated with hemoglobin A1C(HbA1c)(P<0.05).The results provide possibilities for the new discovery of diagnostic markers of GDM,the new therapeutic drugs for GDM and the exploration of the pathological mechanism of GDM.