| BackgroundDiabetes kidney disease(DKD)is the main cause of global renal failure(RF).Its prevalence rate has increased year by year in the past 30 years,accounting for more than50% of patients entering dialysis or transplantation.The American diabetes Association defines DKD as a progressive kidney disease related to diabetes.The diagnostic criteria are that the glomerular filtration rate of diabetes patients is<60ml/min/1.73m2 or proteinuria occurs.20-40% of diabetes patients have DKD.diabetes patients have no obvious clinical manifestations of early renal injury.Most patients have irreversible renal injury when there are obvious clinical manifestations.Once the disease progresses to end-stage renal disease,renal replacement therapy may be the only option.Early detection and intervention can reduce and delay the progression of diabetes nephropathy to end-stage nephropathy.Therefore,it is important to screen early and accurate biomarkers of DKD.The pathogenesis of DKD is complex.Besides the toxic effect of hyperglycemia,oxidative stress,metabolic disorder,inflammation and fibrosis also play an important role.In recent years,many researchers have proved that inflammatory pathways and proinflammatory cytokines play a key role in the occurrence and progress of DKD.However,there are few reports about the efficacy of inflammatory markers in the early diagnosis of DKD.In this study,the neutrophil/lymphocyte ratio(NLR),serum cystatin C(Cys C)and β2microglobulin(β2-MG)were measured and analysed in patients with different stages of Type 2 Diabetes Mellitus(T2DM),and further evaluated whether the combination of NLR,serum Cys C and β2-MG could improve the early diagnosis of DKD and predict the development of renal decline in patients with type 2 diabetes mellitus.MethodA total of 130 hospitalized T2 DM patients admitted to the Department of Endocrinology of Zhecheng County People’s Hospital from October 2021 to June 2022 were selected as the study subjects,including 70 males and 60 females.All patients with T2 DM included in the study met the 1999 World Health Organization(WHO)diagnostic criteria for diabetes mellitus.According to the urine albumin-to-creatinine ratio(UACR),T2 DM patients were divided into three groups:(1)Simple DM group: UACR<30mg/g,a total of 40 cases;(2)microalbuminuria Group: 30mg/g≤UACR<300mg/g,a total of 45cases;(3)Massive albuminuria group: UACR≥300mg/g,a total of 45 cases.Exclusion criteria:(1)Type 1 diabetes(T1DM),gestational diabetes and special types of diabetes;(2)With acute complications of diabetes(such as diabetic ketoacidosis);(3)Acute and chronic nephritis or other diseases that can cause proteinuric hematuria;(4)Recent use of hormones,immunosuppressants or diuretics;(5)Any type of cancer,anemia,severe cardiovascular and liver disease;(6)Maintenance dialysis patients;(7)With acute infection.(8)People with hypertension leading to proteinuria;(9)People with obesity leading to proteinuria.General information such as gender,age,body mass index(BMI),systolic blood pressure(SBP)and diastolic blood pressure(DBP)were recorded for all subjects.and fasting blood glucose(FBG),glycated haemoglobin(Hb Alc),total protein(TP),albumin(ALB),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),urea nitrogen(BUN),serum creatinine(Scr),uric acid(UA),serum cystatin C(Cys C),β2-microglobulin(β2-MG),haemoglobin(Hb),sedimentation(ESR),C-reactive protein(CRP),complement C3,complement C4,calcitoninogen(PCT),parathyroid hormone(PTH),white blood cell count(WBC),neutrophil count,neutrophil percentage,lymphocyte count,lymphocyte percentage,monocyte count,and monocyte percentage,etc.,to calculate NLR,statistical analysis:(1)Comparison of general information and laboratory test results of the three study groups;(2)Comparison of changes in levels of NLR,serum Cys C and β2microglobulin in the three study groups;(3)Pearson or Spearman correlation analysis was applied to explore the correlation between NLR,serum Cys C,β2 microglobulin levels and various laboratory tests in the three study groups;(4)Application of ROC to explore the value of NLR,serum Cys C and β2 microglobulin alone and in combination in predicting the development of early DKD in patients with simple diabetes;(5)Application of ROC to investigate the value of NLR,serum Cys C and β2 microglobulin alone and in combination in predicting impaired renal function in patients with T2 DM.Result1.There was no significant difference among the three groups in gender,age,SBP,DBP and Hb A1 c levels(P>0.05).The renal function indexes BUN,Scr and inflammatory index ESR in the massive albuminuria group were significantly higher than those in the simple diabetes group and the microalbuminuria group,with statistically significant differences(P<0.05).The glomerular filtration rate(e GFR),TP,ALB,Hb and lymphocyte count in the massive albuminuria group were significantly lower than those in the simple diabetes group and the microalbuminuria group,with statistically significant differences(P<0.05).2.NLR levels were significantly higher in the massive albuminuria group than in the diabetes alone group,with a statistically significant difference(P<0.01),and there was no statistically significant difference between the microalbuminuria and diabetes alone groups(P>0.05).For serum Cys C levels,the massive albuminuria and microalbuminuria groups were statistically significantly higher than the diabetes alone group,with a statistically significant difference(P<0.001),while the massive albuminuria group was higher than the microalbuminuria group,with a statistically significant difference(P<0.05).For bloodβ2-MG levels,the massive albuminuria group was higher than the microalbuminuria group,with a statistically significant difference(P<0.001),and the microalbuminuria group was higher than the diabetes mellitus alone group,with a statistically significant difference(P<0.01).3.Correlation analysis showed that among the three groups of subjects,NLR was positively correlated with ESR,Scr and BUN(P<0.05),and negatively correlated with e GFR,Hb,TP and ALB(P<0.05).serum Cys C,β 2-MG was positively correlated with Scr,BUN,UACR,PCT,ESR,CRP(P<0.05),and negatively correlated with e GFR,Hb,TP,ALB(P<0.05).4.The ROC analysis results of NLR,serum Cys C,β 2-MG levels predicting the development of early DKD(microalbuminuria)in patients with simple type 2 diabetes showed that the area under the curve for early diagnosis of DKD by NLR was 0.703(P=0.001),the best cut-off value was 1.925mg/L,the sensitivity was 77.8%,and the specificity was 75.0%.the area under the curve of serum Cys C in diagnosing early DKD was 0.932(P<0.001),the standard error was 0.025,the optimal cut-off value was0.930mg/L,the sensitivity was 98.5%,and the specificity was 75.0%.The area under the curve of β2-MG for early diagnosis of DKD was 0.911(P<0.001),the best cut-off value was 1.450 mg/L,the sensitivity was 81.2%,and the specificity was 67.5%.NLR,serum Cys C and β2-MG of the area under the curve was the largest,AUC was 0.961,sensitivity and specificity were 98.5% and 80.0% respectively.5.The ROC curve analysis of NLR,serum Cys C and β2-MG levels predicting renal function damage in diabetes patients showed that the area under the curve predicted by NLR for renal function damage in diabetes patients was 0.886(P<0.001),the optimal cut-off value was 2.840 mg/L,the sensitivity was 84.6%,and the specificity was 85.7%.the area under the curve of serum Cys C predicting renal function damage in diabetes patients was 0.857(P=0.001),the optimal cutoff value was 1.250mg/L,the sensitivity was 76.9%,and the specificity was 90.5%.The area under the curve of β2-MG to predict renal function damage in diabetes patients was 0.908(P<0.001),the optimal cut-off value was 2.030mg/L,the sensitivity was 83.1%,and the specificity was 87.5%.The area under the curve of NLR,serum Cys C and β2-MG for predicting renal function damage in diabetes patients by combined detection is the largest,with AUC of 0.934,sensitivity and specificity of 95.6%and 83.6% respectively.Conclusion1.The combined detection of the three indicators of NLR、blood Cys C and β2-MG can improve the diagnostic efficacy of T2 DM patients in the early stage of DKD and in the prediction of renal function impairment in type 2 diabetes patients.2.In addition to the conventional markers of glomerular tubules,NLR,as an index related to inflammatory reaction,regularly monitors the level of NLR in T2 DM patients and correlates with blood Cys C and β The 2-MG joint analysis has a good predictive value for the occurrence of albuminuria and renal function impairment in type 2 diabetes patients,which will help to carry out early intervention and management of diabetes nephropathy. |
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