| BackgroundDiabetes mellitus(DM)is a group of metabolic disease characterized by elevated blood glucose level,and the prevalence rate is increasing year by year.Type 2 diabetes mellitus(T2DM)is still the main type of DM in China.Diabetic kidney disease(DKD),a chronic kidney disease(CKD)caused by DM,is one of the most common chronic complications of DM and an important cause of end-stage renal disease(ESRD).The onset of DKD is hidden and its development is slow in the early stage.If these patients are not detected and treated in time,severe renal injury such as macroalbuminuria,decreased renal function and resistant hypertension may occur in the later stage,and eventually develop into ESRD.Therefore,early diagnosis and treatment of DKD is particularly important for patients with DM.In recent years,studies have found that a variety of inflammatory factors are related to the occurrence and development of DKD,suggesting that inflammation is closely related to the pathogenesis of DKD.The peripheral monocyte(Mono)to high-density lipoprotein cholesterol(HDL-C)ratio(MHR)is a novel inflammatory marker.Taking into account the state of chronic inflammation and dyslipidemia,some studies have proposed that MHR has the ability to predict stroke,coronary heart disease and other atherosclerotic diseases.The peripheral neutrophil(Ne)to lymphocyte(Lym)ratio(NLR)is also considered as a marker of chronic inflammation.NLR combines non-specific inflammation marked by elevated neutrophils with physiological stress marked by lymphocytopenia,reflecting the balance between the two complementary components of the immune system.NLR has been proved to be associated with stroke,coronary heart disease,adverse cardiac outcome and metabolic syndrome.In recent years,a few studies have found that MHR and NLR,as markers of inflammation,are related to the progression of diabetic microvascular complications,such as DKD and diabetic retinopathy(DR).And they can be used as predictors of these diseases.Among these studies,some scholars have found that there is a positive correlation between MHR and NLR in patients with DR,but it is not statistically significant.Both DKD and DR belong to the diabetic microvascular complications,and there are similarities in the pathogenesis of the two diseases.However,there are few studies on the relationship between MHR,NLR and DKD.Whether there is a similar correlation between the two inflammatory markers in DKD is still questionable.ObjectiveTo investigate the correlation between MHR,NLR and kidney disease in patients with T2DM,the feasibility of early diagnosis of DKD and the potential connection between the two markers by comparing the differences of two easily available inflammatory markers,MHR and NLR,in different stages of DKD.MethodsA total of 614 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Zhengzhou University from June 201 5 to August 2019 and 210 healthy controls in the physical examination center of our hospital during the same period were enrolled.The general condition,history of present illness and past history of all subjects were recorded.Height,weight,systolic blood pressure(SBP)and diastolic blood pressure(DBP)were measured.Overnight fasting venous blood samples were collected to detect fasting blood glucose(FBG),glycated hemoglobin(HbA1c),routine blood test,blood lipids,renal function and so on.Random urine was used to detect urinary microalbumin and urinary creatinine,and the urinary albumin to creatinine ratio(UACR)was calculated.Body mass index(BMI),MHR and NLR were calculated too.The echocardiography,blood vessels of neck and lower extremities using color Doppler ultrasound as well as ophthalmoscopy were examined in patients with T2DM.The healthy controls were named N group.According to the UACR level,the patients with T2DM were divided into three groups,DM group(210 cases):UACR<30mg/g,DN1 group(208 cases):30mg/g≤UACR≤300mg/g,DN2 group(196 cases):UACR>300mg/g.According to the chronic kidney disease stages of diabetic patients in the Chinese Clinical Guidelines for the Prevention and Treatment of Diabetic Kidney Disease(2019 Edition),comprehensively considering the UACR and estimated glomerular filtration rate(eGFR)level,the patients in DN1 and DN2 group were subdivided into 3 groups.There are 294 cases in group A(eGFR≥90ml/min/1.73m2 and UACR≥30mg/g),70 cases in group B(60ml/min/1.73m2≤eGFR<90ml/min/1.73m2 and UACR≥30mg/g)and 40 cases in group C(eGFR<60ml/min/1.73m2).The data were processed by SPSS 23.0 software.One-way ANOVA,LSD-t test,Kruskal-Wallis H test,Pearson-X2 test,Pearson product-moment correlation analysis and Spearman rank correlation analysis,Multiple linear regression analysis and Receiver operating curve(ROC)were involved.Taking αa=0.05 as the test level,P<0.05 was considered to be statistically significant.Results1.There was no significant difference in sex,age and PLT among the four groups.The monocytes in N group,DM group,DN1 group and DN2 group increased sequentially,while HDL-C decreased in order(P<0.05).The levels of BMI,SBP and neutrophil counts in DN2 group were significantly higher than those in the other three groups(P<0.05).2.The course of DM and MHR increased successively in the four groups,and there were significant differences between every two groups(P<0.05).In patients with T2DM,NLR increased with the increase of UACR level,and the difference was statistically significant(P<0.05),but there was no significant difference in NLR between N group and DM group(P>0.05).The FBG in three groups of T2DM patients was higher than that of N group,while the FBG in DN1 group was highest,and the differences were statistically significant(P<4.05).HbA1c in T2DM group was higher than that in N group,HbAlc in DM group and DN1 group were higher than that in DN2 group,these differences were statistically significant(P<0.05).But there was no significant difference in HbAlc between DM group and DN1 group(P>0.05).The eGFR level of DN2 group was significantly lower than that of other three groups(P<0.05),but there was no significant difference among the three groups(P>0.05).3.The course of DM in group B and C were significantly higher than those in group A(P<0.05),HbA1c in group B and C were significantly lower than those in group A(P<0.05),but there was no significant difference between the two groups(P>0.05).MHR,NLR,UACR and the frequency of macrovascular disease increased successively in group A,B and C,and there were significant differences among any two groups(P<0.05).The frequency of retinopathy in group C was significantly higher than that in the other two groups(P<0.05),while there was no significant difference between group A and B(P>0.05).4.MHR and HbAlc(r=-0.228,P<0.01),WBC(r=0.436,P<0.01),neutrophil(r=0.361,P<0.01),lymphocyte(r=0.091,P<0.05),monocyte(r=0.816,P<0.01),triglyceride(r=0.1 37.P<0,01),HDL-C(r=-0.658,P<0.01),eGFR(r=-0.372,P<0.01),UACR(r=0.482,P<0.01)were significant correlated.There was no correlation between FBG,total cholesterol,LDL-C and MHR(P>0.05).NLR and WBC(r=0.299,P<0.01),neutrophil(r=0.648,P<0.01),lymphocyte(r=-0.588,P<0.01),monocyte(r=0.146,P<0.01),HDL-C(r=-0.116,P<0.01),eGFR(r=-0.335,P<0.01),UACR(r=0.296,P<0.01)were significant correlated.There was no correlation between FBG,HbAlc,total cholesterol,triglyceride,LDL-C and NLR(P>0.05).In addition,there was a significant correlation between MHR and NLR(r=0.169,P<0.01).5.Multivariate liner regression analysis demonstrated that lg(UACR)was independently associated with MHR,eGFR,NLR and the course of DM(β=0.890,95%CI0.807～0.972,P=0.000;β=-0.007,95%CI-0.010～-0.005,P=0.000;β=0.111,95%CI0.059～0.163,P=0.000;β=0.009,95%CI0.002～0.016,P=0.013).And eGFR was independently associated with UACR,the course of DM,HbAlc,and NLR(β=-0.013,95%CI-0.015～-0.012,P=0.000;β=-0.684,95%CI-0.886～-0.481,P=0.000;β=1.574,95%CI0.986～2.163,P=0.000;β=-3.329,95%CI-4.883～-1.774,P=0.000).6.ROC curve showed that the area under the curve of MHR was 0.949(P<0.01),95%confidence interval was(0.934,0.964),the optimal cutoff value was 1.17/ng,and corresponding Youden index,sensitivity and specificity were 0.718,0.903 and 0.814 respectively.The area under the curve of NLR was 0.657(P<0.01),95%confidence interval was(0.611,0.702),the optimal cutoff value was 1.85,and corresponding Youden index,sensitivity and specificity were 0.266,0.604 and 0.662 respectively.The area under the curve of MHR combined with NLR was 0.951(P<0.01),95%confidence interval was(0.936,0.965),the corresponding Youden index,sensitivity and specificity were 0.727,0.770 and 0.957 respectively.Conclusions1.The progression of DKD in T2DM patients is accompanied by an increase in MHR and NLR.2.MHR and NLR are independent predictors of the UACR level.And NLR is an independent predictor of the eGFR level. |
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