Adipokine Metabolism And Gestational Diabetes

Changes in carbohydrate and lipid metabolism occur during pregnancy to ensure a continuous supply of nutrients to the growing fetus despite intermittent maternal food intake.These metabolic changes are progressive and may be accentuated in women who develop gestational diabetes mellitus(GDM).GDM is defined as carbohydrate intolerance that begins or is first recognized during pregnancy.It occurs in 3%-5%of pregnant women and is associated with adverse effects for both mother and fetus.Its pathophysiology is insulin resistance and abnormal insulin secretion.Nowadays the exact pathogenesis of GDM is still not fully understood.Considering the views of the past,alterations in the hormonal milieu during pregnancy(cortisol,estrogens,and progestins,etc.) were probably responsible for the reduced insulin sensitivity.However,in recent years,adipose tissue and its secreted cytokines gradually arouse the attention of scientists.Numerous studies pointed out that adipose tissue also functions as an endocrine organ,which can synthesize and secrete of a large number of peptide hormones related to metabolism such as retinal binding protein 4(RBP4),adiponectin,visfatin,tumor necrosis factor-alpha(TNF-α),and interleukin-6(IL-6),ect..These functional proteins or cytokines are called adipokines,which serve as the endogenous signal molecules,that playing an active role in controlling whole body energy homeostasis and directly regulating insulin sensitivity.The dysfunction of adipokine metabolism can cause low-grade chronic inflammatory state of the body,thus profoundly affecting glucose/lipid metabolism and finally resulting in the development of IR.Therefore,we hypothesised that the changes in adipokine metabolism during pregnancy are in fact in a special regulatory network.The adipokines involved in the complicated network,which have mutual influences and mutual constraints,regulate metabolism accurately.But the mechanism of the adipokines functioning as a whole is still poorly understood.In order to invetigate the role of adipokines in the pathogenesis of IR and GDM, we evaluated maternal and fetal serum concentrations of adipokines and a variety of other parameters in both normal pregnant women and women with GDM.Section 1 Correlation of maternal adipokines,IR and enery metabolism in normal pregnancy and GDMObjective:To explore the maternal changes of adipokines and their correlations with gestational IR and metabolism changes,and the mechanism they involved in the pathogenesis of GDM.Methods:Fifteen women with GDM as an experimental group and twenty healthy age-matched pregnant women as a control group were investigated in a case-control study.We collected the fasting blood before and after delivery between the two groups.Serum RBP4,adiponectin,visfatin, TNF-αand IL-6 were determined by ELISA.Serum insulin was determined by ELA.And a variety of other parameters were also observed.Differences between groups were evaluated with a Student t test.Spearman rank correlation were carried out to determine the relationship between the variables.All tests were two tailed,and the significance level was defined as P＜0.05.Results:Compared with maternal serum in normal pregnancy,higher concentrations of maternal serum TNF-α,RBP4,IL-6,visfatin,insulin, HOMA-IR and TG as well as lower concentrations of maternal serum adipnectin in GDM were observed before and after delivery.Maternal serum levels of glucose increased at delivery and decreased after delivery. Maternal serum concentrations of TC,HDL,LDL and apoA were similar between two groups before and after delivery.In control group a lower trend of maternal serum concentrations of adiponectin,IL-6,RBP4, visfatin,HOMA-IR,TG and apoA were found after delivery,companied with a higher trend of maternal serum concentrations of TNF-αand glucose. Maternal serum concentrations of TC,HDL and LDL were similar before and after delivery.In GDM group a lower trend of maternal serum concentrations of TNF-α,RBP4,visfatin,glucose,insulin,HOMA-IR,TG and apoA were found after delivery.Maternal serum concentrations of adiponectin,IL-6,TC,HDL and LDL were similar before and after delivery. RBP4 levels positively correlated with TNF-α,HOMA-IR and insulin levels, IL-6 levels were positively correlated with insulin levels. Conclusions:The changes in adipokine metabolism during pregnancy are in a special regulatory network.The adipokines involved in the complicated network have been discovered with a variety of biological functions, including energy balance,glucose homeostasis,or lipid metabolism.The dysfunction of adipokine network can cause low-grade chronic inflammatory state of the whole body,thus profoundly affecting glucose/lipid metabolism and finally resulting in the development of IR.When pancreatic beta cell function is unable to compensate for this insulin resistance, GDM occurs.Section 2 Correlation of maternal and Fetal adipokines and enery metabolism in normal pregnancy and GDMObjective:To explore the maternal and fetus alterations of adipokines and their correlations with fetus metabolismMethods:Fetal serum RBP4,adiponectin,visfatin,TNF-αand IL-6 were determined by ELISA,while insulin was determined by ELA in twenty normal pregnant women and fifteen women with GDM.And a variety of other parameters were also observed.Differences between groups were evaluated with a Student t test.Spearman rank correlation were carried out to determine the relationship between the variables.All tests were two tailed,and the significance level was defined as P＜0.05.Results:Compared with maternal serum in normal pregnancy,higher concentrations of fetal serum TNF-α,adiponectin,IL-6,and visfatin, as well as lower concentrations of fetal serum RBP4 and insulin were observed although the difference had no significance.While compared with maternal serum in GDM,higher concentrations of fetal serum adiponectin and IL-6,as well as lower concentrations of fetal serum TNF-α, adiponectin,RBP4 and insulin were observed.Compared with fetal serum in normal pregnancy,fetal serum concentrations of TNF-αand insulin were markedly increased in GDM,as well as fetal serum concentrations of adiponectin were markedly decreased in GDM,accompanied with a higher level of IL-6,visfatin and a lower level of RBP4 but without statistical significance.Conclusions:Adipokines play an important role in regulating fatal tissue differentiation,and fatal energy metabolism.Fetus in GDM has adipokine network disorders in uterus.