| AimThis study aimed to investigate the relationship between serum Isthmin 1(Ism-1)levels and DKD in patients with T2DM.MethodsIt is a retrospective study.All T2DM inpatients in department of endocrinology in Qilu Hospital of Shandong University from October 2020 to December 2021 were recruited as participants.Fasting serum,general data and laboratory data were collected.Based on the age,gender,and creatinine,eGFR was calculated according to the CKD-EPI equation.ELISA was used for measurement of serum Ism-1 levels.All analyses were performed with SPSS 25.0 software.Independent t test or Mann-Whitney U test were chosen for evaluating statistical significance of differences between two groups according to distribution of variables.Comparisons between groups were evaluated using one-way ANOVA and LSD post hoc test or Kruskal-Wallis test according to distribution of variables.Pearson or Spearman correlation analysis were adopted to evaluate the association between serum Ism-1 levels and UACR,eGFR or other variables according to the type and distribution of variables.Logistic regression and linear regression analyses were used to assess the association of serum Ism-1 levels with UACR and eGFR.ROC curve was constructed to determine the best threshold value of Ism-1 for distinguishing patients of different eGFR stages.IHC was used to explicit location and levels of Ism-1 in human kidney of normal control and DKD patients.Results1.The relationship between serum Ism-1 levels and UACR in T2DM patients with eGFR≥60ml/min/1.73m2All participants were stratified into normal-albuminuria group,microalbuminuria group and microalbuminuria group:normal-albuminuria was defined as<30mg/g;microalbuminuria was defined as UACR ranging from 30mg/g to 300mg/g and macroalbuminuria was defined as UACR>300mg/g.Compared with normal-albuminuria and microalbuminuria group,serum Ism-1 levels were significantly higher in the macroalbuminuria group(p<0.05).Logistic regression analyses showed that serum Ism-1 levels were positively associated with odds of albuminuria(OR=3.3570,p<0.05).Linear regression analyses showed that serum Ism-1 levels were positively associated with logio-transformed UACR(p=0.625,p<0.01).2.The relationship between serum Ism-1 levels and eGFR in T2DM patientsAccording to guideline for the prevention and treatment of type 2 diabetes mellitus in China(2020 edition),all T2DM patients were divided into four stages based on the eGFR:G1(eGFR>90 mL/min/1.73m2),G2(eGFR 60-89 mL/min/1.73m2),G3(eGFR 30-59 mL/min/1.73m2),G4-5(eGFR<30 mL/min/1.73m2),eGFR<60 mL/min/1.73m2 was defined as declined GFR.Compared with G1 or G2 groups,serum Ism-1 levels were higher in G3 and G4-5 groups(p<0.001).Logistic regression analyses showed that serum Ism-1 levels were positively associated with odds of declined GFR(OR=1.545,p<0.001).Linear regression analyses showed that serum Ism-1 levels were negatively correlated with eGFR in patients with T2DM(β=-37.064,p<0.001).ROC analysis showed that serum Ism-1 levels could effecitively identify different eGFR stages.The optimal cut-off value of Ism-1 to diagnose declined eGFR(eGFR<60 mL/min/1.73m2)was 1.297 ng/mL(AUC=0.908).The sensitivity and specificity values were 92.86%and 83.83%.3.The relationship between serum Ism-1 levels and DKD in T2DM patientsT2DM patients with UACR>30mg/g and/or eGFR<60 ml/min/1.73m2 were diagnosed as DKD patients,while T2DM patients with UACR<30mg/g and eGFR≥60 ml/min/1.73m2 were included into Non-DKD group.Serum Ism-1 levels of patients in DKD group was significantly higher than patients in Non-DKD group(p<0.001).Logistic regression analyses show that increased serum Ism-1 level was an independent risk factor for patients with T2DM(OR=1.249,p<0.001).4.Differences of serum Ism-1 levels in different DKD progression risk groupsAccording to KDIGO guideline,T2DM patients were divided into four different DKD progression risk:low-risk,intermediate-risk,high-risk,and very high risk group.Serum Ism-1 levels in very high-risk group were higher than the other three groups(p<0.05).Serum Ism-1 levels in high-risk group were higher than low-risk group and intermediate group(p<0.05).5.Immunohistochemistry(IHC)shows the location and levels of Ism-1 in human kidneyBased on IHC,the expression of Ism-1 was observed mainly in human renal tubules.Compared with the control group,the Ism-1 levels were significantly increased in patients with DKD.6.The relationship between serum Ism-1 levels and other indexes in T2DM patients:No significant association was observed between serum Ism-1 levels and BMI or body composition indices(p>0.05).Serum Ism-1 levels were negatively associated with HDL-C(p<0.01)and positively related to TG(p<0.05)in female T2DM patients,while no clear correlation was detected between serum Ism-1 levels and blood lipid indexes in male T2DM patients.Conclusions1.In T2DM patients with eGFR≥60ml/min/1.73m2,serum Ism-1 levels were significantly higher for patients with macroalbuminuria.Serum Ism-1 was positively associated with log10 UACR.Increased serum Ism-1 level was an independent risk factor for albuminuria in patients with T2DM.2.Serum Ism-1 levels were increased in T2DM patients with eGFR<60 ml/min/1.73m2.Serum Ism-1 levels were negtively associated with eGFR.Increased serum Ism-1 level was an independent risk factor for declined GFR in patients with T2DM.Serum Ism-1 level could be used as a potential biomarker for identifying different eGFR stages in patients with T2DM.3.T2DM patients with DKD had higher serum Ism-1 levels than T2DM patients without DKD.Increased serum Ism-1 level was an independent risk factor for DKD in patients with T2DM.4.Serum Ism-1 levels in very high-risk group were higher than the other three groups.Serum Ism-1 levels in high-risk group were higher than low-risk and intermediate group.5.The expression of Ism-1 was located in human renal tubules.Compared with control group,the Ism-1 levels were significantly higher in patients with DKD.6.Serum Ism-1 levels had a significantly negative association with HDL-C and positive association with TG in female T2DM patients.No clear correlation was detected between serum Ism-1 levels and blood lipid indexes in male T2DM patients. |
