The Study Of Role Of Adiponectin And Its Receptor In The Pathogenesis Of GDM And Analysis Of Related Factors

Backgrouds and objectivesGestational diabetes mellitus(GDM),a form of glucose intolerance which occurred during pregnancy,could do great harm to the health of pregnant women and fetus,and has been known for being closely correlated with poor outcomes of gestation.GDM is a risk factor for the later development of type 2 diabetes,and timely intervention to GDM may not only significantly decrease the mortality rate of fetus during perinatal period,but delay the onset of type 2 diabetes in women.Both insulin resistance and beta cell dysfunction have been thought being involved into the pathogenesis of GDM,while chronic insulin resistance share common mechanism in GDM and type 2 diabetes.Previous studies have found that C-reactive protein(CRP) and IL-6 are the predictors for type 2 diabetes, however whether cytokines could predict the onset of GDM or play an critical role in the progression of GDM still is unknown.Free fatty acids(FFA) is the critical factor in the metabolism of lipid.It has been reported that elevated level of plasma FFA in type 2 diabetes subjects is an independent risk factor,and could lead to insulin resistance and increased apoptosis rate of beta cells,which may be conducted by the inflammation.Adiopnectin,one of the most important adipokines, is believed to possess the bioactivity like anti-inflammation,anti-diabetes,anti-artherosclerosis and improve insulin sensitivity.Not surprisingly,the level of plasma adiponectin was decreased in the type 2 diabetes patients.The studies concerning the association between GDM and adiponectin are few,though many have been done in the fields of its involvement in type 2 diabetes.In the present study,80 subjects were stratified into three groups according to the fasting and 2h blood glucose:GDM group,normal glucose tolerance with gestation group and normal glucose.tolerance without gestation group.The expression level of adiponectin and its receptor in subcutaneous/abdominal fat and muscle was compared in these groups, so did other cytokines and FFA.Furthermore,the association between adiponectin and its receptor and insulin resistance in GDM was also assessed in this study.The measurements of serum CRP,adiponectin and FFA were then performed in these subjects,and the expression level of adiponectin and its receptor was detected in subcutaneous fat, abdominal fat and muscle tissues from these groups by using RT-PCR.Subjects and methodsBased on the results of 75g oral glucose tolerance test,90 subjects were stratified into three groups according to the fasting and 2h blood glucose:GDM group,normal glucose tolerance with gestation group and normal glucose tolerance without gestation group. Anthropometric measurements included:height,weight,body mass index(BMI,kg/m~2). Blood samples for measurements of free fatty acid(FFA) and C peptide,total cholesterol (TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol (HDL-C),triglyceride(TG) and CRP levels were collected after an overnight fast.Plasma glucose was assayed by an automated glucose oxidase method.Insulin was determined by RIA.The concentration of serum adiponectin was measured by ELISA method.The homeostasis model(HOMA) model was adopted to calculate the index of insulin resistance HOMA-IR=FINS×FPG/22.5) and beta cell function(HOMA-β=20×FINS/(FPG-3.5)).The expression level of adiponectin and its receptor was detected in subcutaneous fat, abdominal fat and muscle tissues from these groups by using RT-PCR.The study was designed in compliance with the ethics regulations set out by the Helsinki Declaration,and all subjects were well informed about the study before the consent was acquired.Results1.During the period between 38-40 weeks after gestation,①The level of adiponectin was gradually decreased from NC group,NGT group to GDM group,and the difference between among these groups was significant(P＜0.05);The level of FFA was gradually increased from NC group,NGT group to GDM group,and the difference among these groups also was significant(P＜0.05);The level of CRP in GDM group was higher than those of NGT and NC group respectively(P＜0.05).②In GDM group,the plasma level of adiponectin was negatively correlated with HOMA-IR(r=-0.560,P＜0.01),while the plasma level of FFA and CRP was positively correlated with HOMA-IR respectively(r=0.515,P＜0.01;r=0.640,P＜0.01);③Stepwise regression analysis indicated that CRP,BMI(before gestation) and adiponectin was the last ones enter the equations,when HOMA-IR was taken as dependent variable.While in the stepwise regression analysis,in which adiponectin was taken as dependent variable,CRP and weight entered the equations last.2.During the period from38-40 weeks after gestation,①The mRNA expression of adiponectin and its receptor in subcutaneous and abdominal fat was gradually decreased from NC group to GDM group(P＜0.05).②In GDM group,the mRNA expression of adiponectin in subcutaneous adipose tissue was positively correlated with HOMA-β,and the level of LDL-C;the mRNA expression of adiponectin in abdominal adipose tissue was negatively correlated with FPG, FINS and HOMA-IR;the mRNA expression of adiponectin receptor was negatively correlated with FPG,HOMA-IR,TC and TG.Conclusions(1) GDM subjects has increased insulin resistance,and CRP,BMI(before gestation) and plasma adiponectin was independently associated with IR,which demonstrated that the insulin resistance was involved in the onset of GDM.(2) The level of CRP and FFA was higher in GDM than that of gestation group with normal glucose tolerance,which suggested the chronic inflammation was associated with lipidemia and insulin resistance.The level of plasma adiponectin was significantly decreased in GDM,and negatively correlated with HOMA-IR,which indicated that the adiponectin played an role in the insulin resistance and the onset of GDM.(3) The level of mRNA expression of adiponectin in subcutaneous adipose tissue was significantly decreased in GDM subjects than those of gestation group and normal control, while the abdominal tissue decreased even more,indicating its role in GDM.(4) The mRNA expression of adiponectin in abdominal adipose tissue in GDM was negatively correlated with FPG,FINS and HOMA-IR,which suggest that the adiponectin in abdominal adipose tissue is involved in the development of insulin resistance.(5)The level of mRNA expression of adiponectin receptor 1 in muscle tissue was lower than that in normal gestation group and control group.(P＜0.05),which means this decrease was closely correlated with glucolipid metabolism and insulin resistance.