Correlation Analysis Between Lipoprotein-related Phospholipase A2 Level And Stage Of Nephropathy In Type 2 Diabetic Subjects

BackgroundsLipoprotein-associated phospholipaseA2(LP-PLA2),also regarded as a platelet-activating factor acetylhydrolase(PAF-AH),is mainly secreted by mononuclear macrophages,T lymphocytes and mast cells,can hydrolyze and oxidize the phospholipid component in low-density lipoprotein(LDL),produce lipid pro-inflammatory substances,which can cause atherosclerosis and pro-inflammatory effects,thereby damaging vascular endothelial cells and causing dysfunction of blood vessels.In recent years,studies at home and abroad have found that LP-PLA2 is involved in the development of various diseases in the body,such as coronary heart disease,cerebrovascular disease,metabolic syndrome,etc.and can be used as an independent risk factor for predicting the development of cardiovascular and cerebrovascular diseases.Inhibitors of LP-PLA2 can delay and protect the function of the corresponding tissues and organs,delay the occurrence and development of the disease,and improve the prognosis.Diabetes(DM)is a group of metabolic diseases characterized by chronic hyperglycemia caused by multiple causes.The pathogenesis is mainly insulin secretion and function defect.In recent years,with the changes of people's lifestyles,the incidence of type 2 diabetes(T2DM)has increased year by year,and is closely related to factors such as insulin resistance(IR)and impaired insulin secretion.Diabetic nephropathy(DN)is one of the most common chronic microangiopathy of T2 DM,and it is also one of the leading causes of end-stage renal disease(ESRD)and diabetes' death,which has brought enormous economic burden to society and individuals.Most studies at home and abroad have shown that LP-PLA2 concentrations are associated with fasting blood glucose and IR.Studies such as T2 DM patients and diabetic retinopathy mice have found that the expression of LP-PLA2 is increased.Using the LP-PLA2 inhibitor can delay and reduce macular edema,inhibit retinal thickening,and improve retinal function.Diabetic retinopathy(DR)and DN are belong to the same microvascular disease of T2 DM,and there are some common pathogenesis.While there are few studies on the relationship between LP-PLA2 and DN at home and abroad.ObjectiveTo investigate the correlation between lipoprotein-related phospholipase A2(LP-PLA2)levels and the stage of diabetic nephropathy(DN)in type 2 diabetic subjects MethodsA retrospective analysis of T2 DM patients were admitted to the Department of Endocrinology,the First Affiliated Hospital of Zhengzhou University from April 2017 to June 2018,and those who had physical examinations at the physical examination center of our hospital during the same period.Relevant indicators were collected for all subjects,including general condition,age,gender,medical history,smoking history,blood pressure,height,weight,body mass index(BMI),glycated hemoglobin(HbA1C),creatinine(Cr),blood urea nitrogen(BUN),uric acid(UA),Total cholesterol(TCHO),triglyceride(TG),LDL,high density lipoprotein(HDL),fasting blood glucose(FBG),fasting insulin(FINS),serum LP-PLA2 levels.Urinary samples were used to determine the ratio of urinary albumin to creatinine(UACR),calculated the arteriosclerosis index(AI)([TCHO-HDL]/HDL)and Homeostasis Modle-IR(HOMA-IR)([FBG(mmol/L)×FINS(mIU/L)] / 22.5).Perform neck,lower extremity blood vessels and heart ultrasound tests and fundus examination.According to the oral glucose tolerance test(OGTT)results,it was divided into T2 DM group and healthy control group(D group).T2 DM patients were divided into three groups according to UACR results: the stage of DN4 group: UACR>300mg/g,the stage of DN3 group: UACR 30-300mg/g,DM group: UACR < 30 mg / g.Measurement data conforming to the normal distribution are expressed as mean ±standard deviation(x ±s),and non-normal distribution measurement data are expressed by median(M)and interquartile range(IQR).The comparison between multiple groups of measurement data was performed by one-way analysis of variance.When comparing between groups,if the variance was uniform,the LSD test was used.If the variance was not uniform,the LSD-t' test was used.Correlation analysis between factors was performed using Pearson correlation or Spearman rank correlation.Based on the UACR,according to whether the DN is diagnosed,the two-category count is performed,and the working curve of the subject is plotted to determine the diagnostic efficiency of the LP-PLA2.Statistical analysis using SPSS 21.0 software,?=0.05 as a test level,P < 0.05 is considered statistically significant.Results1.There was no significant difference between the T2 DM patients and the normal control group: gender,age,SBP,DBP,BUN,Cr,UA,TCHO,TG,HDL,LDL,AI,smoking history factors(P>0.05).There were significant differences in BMI and HbA1 C between T2 DM patients and normal controls(P<0.05).There was no significant difference between BMI and HbA1 C patients in T2 DM patients(P>0.05).2.With the progress of DN,there were statistical differences in LP-PLA2,FBG,FINS and HOMA-IR between the four groups(P<0.05).There was no significant difference between the stage of DN4 group and the DN3 group in disease course(P>0.05),they were statistically different from DM group and D group(P<0.05).3.Each group was divided into 2 subgroups according to the presence or absence of other vascular lesions(including arterial plaque,cardiovascular disease,and fundus lesions).The results showed that with the increase of DN stage,the level of LP-PLA2 was gradually increased with the inclusion of other blood vessels lesions,The difference was statistically significant(P<0.05).With the increase of DN stage,the level of LP-PLA2 was gradually increased in the patients without other vascular lesions,and the difference was statistically significant(P<0.05).4.Correlation analysis between each variable and LP-PLA2: LP-PLA2 and TCHO(r=0.206,P<0.01),LDL(r=0.213,P<0.01),AI(r=0.176,P<0.05),FBG(r=0.574,P<0.01),FINS(r=0.616,P<0.01),HOMA-IR(r=0.791,P<0.01)and UACR(r=0.638,P<0.01)were positively correlated,There was no correlation between BMI,HbA1 C,HDL and TG with LP-PLA2(P>0.05).5.Correlation analysis between DN and various factors: DN and disease course(r=0.228,P<0.01),FBG(r=0.301,P<0.01),FINS(r=0.517,P<0.01),HOMA-IR(r =0.590,P<0.01),LP-PLA2(r=0.499,P<0.01)showed a positive correlation;no correlation with BMI,BP,TCHO,TG,HDL,LDL,BUN,Cr,UA,HbA1 C,AI(P>0.05).6.Multivariate linear regression analysis demonstrated that UACR was independently associated with HOMA-IR?HbA1C?LP-PLA2?BMI(?= 47.185,95%CI 35.629 ~58.742,P= 0.000;?=-27.579,95%CI-38.055 ~-15.103,P=0.000;?= 0.545,95%CI 0.075~1.106,P=0.023;?=7.305,95%CI 0.007 ~ 14.602,P=0.050).7.The working curve of the receiver showed that the area under the curve of LP-PLA2 is 0.927(P<0.01),the 95% confidence interval is(0.878,975),the optimal cutoff value is 154.00ng/ml,the corresponding Yoden index is 0.763,and the sensitivity is 0.874.The degree is 0.889.The area under the curve of HOMA-IR is 0.934(P<0.01),the 95% confidence interval is(0.897,0.972),the optimal cutoff value is 3.875ng/ml,the corresponding Yoden index is 0.693,and the sensitivity is 0.971.The degree is 0.722.ConclusionsLP-PLA2 is an independent risk factor for UACR,and it gradually increases with the progress of DN in T2 DM patients.LP-PLA2 may participate in the development of DN,and provide new ideas for predicting,diagnosing and treating DN.