Correlation Between Serum EDA Levels And Albuminuria In Patients With Type 2 Diabetes Mellitus

Objective: Ectodysplasin A(EDA)is a novel hepatokine that has been discovered in recent years,which belongs to the tumor necrosis factor family.Previous studies have found that EDA may participate in the regulation of lipid metabolism and insulin sensitivity,also EDA was closely linked to multiple metabolic diseases,for example,obesity and non-alcoholic fatty liver disease.In this study,we intended to further explore the relationship between EDA and albuminuria in individuals diagnosed with type 2 diabetes mellitus.Methods: 248 subjects were chosen to get involved in this study,in which subjects were divided into 189 cases in the T2 DM group and 59 cases in the normal glucose tolerance(NGT)group.All basic parameters were collected and the clinical indicators were measured,and the T2 DM group was further divided into three groups according to urinary albumin/creatinine ratio(UACR): normal albuminuria group(UACR<30mg/g,n=97),microalbuminuria group(30mg/g≤UACR<300mg/g,n=62)and macroalbuminuria group(UACR≥300mg/g,n=30),and the differences in clinical indicators and serum EDA levels were compared among the three groups.According to the traid of EDA level,all subjects were divided into group T1(EDA < 271.54 pg/m L,n=82),group T2(271.54 pg/m L ≤ EDA ≤364.93 pg/m L,n=84)and group T3(EDA > 364.93 pg/m L,n=82),the clinical indicators were compared of these groups.Relevance of EDA to UACR were analyzed.The predictive value of exploring EDA for the development of albuminuria in patients with T2 DM was assessed by receiver operating characteristic(ROC)curve.Results:(1)Compared to the NGT group,the prevalence of diastolic blood pressure(DBP),systolic blood pressure(SBP),body mass index(BMI),age,waist circumference(WC),waist-hip ratio(WHR),fasting blood glucose(FPG),2-hour postprandial glucose(2h PG),glycosylated hemoglobin A1c(Hb A1c),triglyceride(TG),blood urea(BUN),homeostasis model assessment of insulin resistance(HOMA-IR)index,fasting insulin(FIns),and EDA were increased in the T2 DM group,while high-density lipoprotein cholesterol(HDL-C)decreased,the observed differences had statistics significances(P < 0.05).(2)Compared with the normal albuminuria group,EDA,age,SBP,FIns and BUN were significantly higher,e GFR levels were lower in the microalbuminuria and macroalbuminuria groups.The differences were statistically significant(P < 0.05).(3)WC,FCP and Hb1 Ac were significantly higher in group T2 and T3 than group T1;Hb1Ac was significantly higher in group T3 compared with group T2(P < 0.05).(4)Correlation analysis showed a positive correlation between EDA and age,FIns,HOMA-IR,UACR,while a negative correlation with e GFR(P < 0.05).(5)With EDA level as the dependent variable,multiple stepwise regression analysis showed that EDA was independently associated with FIns and UACR(P < 0.05).(6)Multiple linear regression analysis with UACR as the dependent variable suggested that UACR was independently associated with EDA[Beta=0.151,95%CI:0.000～0.002;P<0.05].(7)The occurrence of albuminuria was designated as the dependent variable and the serum EDA level was assigned as the independent variable in the logistic regression analysis(Model 1),the risk of albuminuria was higher in group T2 and T3 compared with group T1.Corrected for sex,age,duration of disease and blood pressure on this basis(model 2),the risk of albuminuria remained higher in group T2 and T3 than in the group T1.Further adjustment for BMI,WHR,history of smoking,history of hypertension,and history of drug use(model3),group T2 and T3 still had an increased risk of albuminuria.(8)The area under the curve for EDA to predict the occurrence of albuminuria was0.701 as the ROC curve analysis showed(95% CI: 0.625-0.777,p < 0.05),the best cut-off value for EDA was 310.47 pg/m L,and the sensitivity and specificity for predicting the occurrence of abnormal albuminuria were 72.8% and 60.3% respectively.Conclusions:Serum EDA levels enhanced with the increases of urinary albumin level in patients with T2 DM,and was independently associated with the occurrence of albuminuria,which has a good predictive value for combined albuminuria in patients with T2 DM,suggesting that EDA may be involved in the development of DKD.