The Relationship Between NLR,PLR,MLR,and SII And Diabetic Peripheral Neuropathy In Type 2 Diabetes Mellitus

Background and objective:Type 2 diabetes peripheral neuropathy(T2DPN)is one of the most frequent chronic complications of type 2 diabetes mellitus(T2DM),and its pathogenesis is extremely complex.At present,some studies have shown that long-term chronic inflammatory response is closely related to peripheral nerve injury.In recent years,the relationship between the level changes of various inflammatory indicators and type 2 diabetes mellitus and its complications are gradually valued.Diabetic peripheral neuropathy is mainly manifested as numbness of limbs,pain,paresthesia,etc.Severe patients will have foot ulcers.If the diagnosis and treatment is not timely,there may even be a risk of amputation.T2DPN seriously affects people’s quality of life,so it is particularly important how T2DM patients find whether they have peripheral neuropathy in time.DPN signs of screening is vulnerable to the subjective interference of patients,and nerve conduction velocity check is mainly used for the detection of medullary nerve fiber function,cannot reflect the function of small nerve fibers,little help to DPN early diagnosis,is not suitable for DPN daily screening means.In this context,we aimed to find a simple and quick detection way to predict the occurrence of type 2 diabetes peripheral neuropathy.The neutrophil / lymphocyte ratio(NLR),monocyte / lymphocyte ratio(MLR),platelet / lymphocyte ratio(PLR),and systemic immune inflammatory index(SII)can reflect systemic inflammation.This study aims to analyze the changing characteristics of NLR,MLR,PLR,and SII in type 2 diabetic patients with peripheral neuropathy to determine its value in predicting T2DPN.Subjects and methods Subjects:A total of 432 patients with T2DM who were hospitalized in the Endocrinology Department of the Affiliated Hospital of Yangzhou University from January 2021 to December 2021 were collected.According to the ADA Standards of Medical Care in Diabetes in 2017 and neuroelectrophysiological findings,the patients were divided into two groups: 316 patients with in the T2DM were associated with peripheral neuropathyand 116 cases with T2DM alone.All patients excluded type 1diabetes and special type of diabetes,severe liver,renal function impairment,coronary heart disease,severe infection,tumor,etc.Methods: Record the collected gender,age,blood pressure of all patients,past history included past history of smoking,history of hypertension and course of diabetes(DM course),and the physical index is calculated according to the height and weight(Body Mass Index,BMI).All patients were fasting for 8h and venous blood was drawn early the next morning and tested by the clinical laboratory center of the hospital to uniformly detect the number of neutrophil number,lymphocyte number,platelet number,fasting blood glucose(FBG),glycated hemoglobin(Hb A 1 c),fasting C-peptide(C-P),2-hour postprandial C-Peptide(120min C-P),lactate dehydrogenase(LDH),aspartate aminotransferase(AST),serum alanine aminotransferase(ALT),glutamyl transpeptidase(GGT),blood creatinine(SCr),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),Low-density lipoprotein cholesterol(LDL-C),etc.The middle urine specimen was kept in the morning,and the urine microalbumin was detected by immunopturbidimetry,and the creatinine concentration was measured by colorimetric method,from which the ratio of urine albumin to urine creatinine UACR(mg / g)was calculated.The collected data will be compared between the groups,and draw the subject operating characteristic curve(ROC).Results:1.Comparison of the basal characteristics between the two groups:Sex,smoking ratio,body mass index,systolic blood pressure,diastolic blood pressure,low-density lipoprotein,high-density lipoprotein,and alanine aminotransferase levels were similar(P> 0.05).The proportion of advanced age,hypertension,arteriosclerosis and arterial plaque in DPN + T2DM group was significantly higher than that in T2DM group(P<0.05).In the DPN + T2DM group,fasting blood glucose,glycated hemoglobin,diabetes duration,triglycerides,cholesterol,blood creatinine,urinary albumin and urinary creatinine levels were higher than those in the T2DM group(P <0.05).The levels of aspartate aminotransferase,transglutamyl transpeptidase,fasting C peptide(C-P),and C peptide at 2 hours after eating were lower than that of the T2DM group(P<0.05).2.Comparison of NLR,PLR,MLR,and SII between the two groups:Compared with the T2DM group,the overall distribution of PLR,NLR,MLR and SII indicators in DPN + T2DM group showed statistical significance(P <0.05).3.The relationship between the basic characteristics of the study subjects and the NLR,MLR,and SII:According to the ROC curve,the optimal cut-off values for NLR,MLR and SII for developing peripheral neuropathy in patients with type 2 diabetes were1.926,0.225 and 319.415 respectively.The subjects were grouped according to optimal cut-offs: high NLR group(NLR> 1.926)and low NLR group(NLR 1.926),high MLR group(MLR> 107.01)and low MLR group(MLR 107.01),high SII group(SII>369.415)and low SII group(SII> 369.415).Compared to patients aged <60 years,Patients aged ≥60 years were more likely to present with NLRhigh(P=0.003)and MLRhigh(P=0.001).Male patients were more likely to show NLRhigh(P=0.003)and MLRhigh(P <0.001);Patients with a duration of diabetes of >5 years were more likely to show MLRhigh than those with a duration of <5 years(P=0.002).Patients with ACR30 mg / g were more likely to show NLRhigh(P=0.001)and SIIhigh(P <0.001)than patients with ACR <30mg / g.Compared with patients without a history of hypertension,patients with combined hypertension were more likely to show MLRhigh(P=0.012).There was no statistical association between the remaining essential features and the NLR,MLR,and SII(P> 0.05).4.Multivariate analysis of the patients influencing peripheral neuropathy in type 2diabetes: Patients aged ≥60 years had a higher incidence of DPN,and it was statistically significant(OR = 3.106,95%CI 1.848-5.233,P<0.05).The duration of diabetes at more than 5 years increases the risk of DPN,and it was statistically significant(OR = 2.028,95%CI 1.229-3.347,P<0.05).Patients with high fasting glucose had a significantly higher risk of DPN than low fasting glucose,the difference was statistically significant(OR = 1.547,95%CI 1.086-2.203,P<0.05).The incidence of DPN was significantly higher in patients in the high NLR group than in patients in the low NLR group,the difference was statistically significant(OR=2.269,95%CI1.239-4.155,P<0.05).Compared with the patients in the low SII group,patients with the higher SII group had a higher risk of DPN,the difference was statistically significant(OR = 2.841,95%CI 1.477-5.467,P<0.05).5.To construct combined predictors of peripheral neuropathy in type 2diabetes:Joint predictor =-1.277 + 1.133 *(age)+ 0.707 *(DM course)+ 0.436 *(FBG)+ 0.819 *(NLR)+ 1.044 *(SII),the cutoff point for the joint predictor was-0.211 and the area under the ROC curve was 0.770(95% CI 0.727～0.809).6.Comparison of the predictive value of NLR,MLR,SII,and the combined predictors for developing DPN in patients with T2DM:The best cut-off values for NLR,MLR and SII for DPN were 1.926,0.225 and 319.415,respectively,the area under the curve were 0.724,0.620 and 0.680,all greater than 0.5,the specificity was 76.72%,78.45% and 81.9%,and the sensitivities were 57.28%,44.62% and 50%,respectively.The cutoff point of the combined predictor regarding DPN was-0.211 and the area under the curve was 0.770,with a specificity of 73.28% and a sensitivity of 70.89%.The area under the ROC curve of NLR predicting DPN in T2DM is greater than MLR(Z=3.632,P <0.001)and SII(Z=2.163,P<0.05).The area under the ROC curve of Joint predictor predicting DPN in T2DM is greater than the MLR(Z=1.731,P <0.001),SII(Z=3.352,P<0.001)and NLR(Z=1.957,P<0.05).There was no difference between MLR and SII(Z=1.731,P=0.083).Conclusion:The levels of NLR,PLR,MLR,and SII are closely associated with type 2 diabetic peripheral neuropathy,with NLR and SII being independent risk factors for developing peripheral nerve injury in patients with T2DM.The combined predictors had better predictive efficacy of T2DPN occurrence than a single index.