Predictive Value Of Neutrophil-to-Lymphocyte Ratio And Monocyte-to-High-density Lipoprotein Cholesterol Ratio For Osteoporosis In Postmenopausal Patients With Type 2 Diabetes Mellitus

BackgroundWith the improvement of people’s life quality and the change of dietary structure,the prevalence of diabetes has increased significantly.A large number of studies have shown that patients with diabetes have a significantly increased risk of developing osteoporosis(OP)compared with those without diabetes.Diabetic osteoporosis(DOP)is a chronic complication of diabetes in skeletal system,which is mainly manifested as decreased bone strength,increased bone fragility and prone to fracture.The pathophysiological mechanism of DOP is complex and not yet fully understood,which is considered to be related to a variety of factors such as hyperglycemia,accumulation of advanced glycation end products(AGEs),insufficient effect of insulin,oxidative stress and chronic inflammation.Chronic inflammation is not only involved in the the pathogenesis of diabetes,but also closely related to occurrence and development of OP.Previous studies have shown that patients with diabetes have an enhanced inflammatory response and increased production of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and other inflammatory factors,which can induce osteoclast production and promote bone resorption,suggesting that chronic inflammation is closely related to the occurrence of DOP.Neutrophil to lymphocyte ratio(NLR)and monocyte to high-density lipoprotein cholesterol ratio(MHR)are two newly discovered inflammatory markers.Compared with the traditional inflammatory indicators such as TNF and IL,they are economical,practical,and easy to measure.At present,numerous studies have confirmed that NLR and MHR were related to various diseases such as coronary heart disease,diabetes and malignant tumors.The latest research indicated that NLR and MHR were negatively correlated with bone mineral density(BMD)in postmenopausal women,and both of them could predict the occurrence of OP.Postmenopausal type 2 diabetes mellitus(T2DM)patients have multiple risk factors such as diabetes,advanced age and estrogen deficiency,and the risk of DOP is greatly increased.Therefore,early diagnosis and treatment of DOP is crucial for postmenopausal T2DM patients.However,there are few studies on NLR and MHR predicting OP in postmenopausal T2DM patients all over the world and they generally focus on one single indicator.In this study,both NLR and MHR were included to evaluate the predictive value of NLR,MHR and their combination for OP in postmenopausal T2DM patients.ObjectiveTo analyze the correlation between NLR,MHR and bone mineral density in postmenopausal T2DM patients,and to evaluate the predictive value of NLR,MHR and their combination for osteoporosis in postmenopausal T2DM patients.MethodsThree hundred and four postmenopausal T2DM patients who were admitted to the Department of endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2021 were selected retrospectively.All patients met the inclusion and exclusion criteria of this study.General data and relevant biochemical indicators of patients were collected,and NLR and MHR were calculated.We measured the BMD of lumbar spine(L1-L4),left femoral neck and left hip by means of dual energy X-ray absorptiometry(DXA),the mean BMD of lumbar spine(Li-L4)was used as L1-4BMD.According to the BMD,all patients were divided into normal bone mass group(n=92),osteopenia group(n=98)and osteoporosis group(n=114).Additionally,patients were divided into four groups according to the NLR and MHR quartiles.Non-parametric test was used to compare the differences of indicators among the groups and Spearman rank correlation was used to analyze the correlation between various factors and the BMD of different parts.Univariate and multivariate logistic regression analysis was conducted to explore the related factors of OP in postmenopausal T2DM patients.Receiver operating characteristic curve(ROC curve)was plotted to evaluate the predictive value of NLR,MHR and their combination for OP in postmenopausal T2DM patients.P<0.05 means the difference is statistically significant.Results1.Comparison of clinical data among the groups with different BMD levelsThere were statistically significant differences in age,menopausal duration,course of diabetes,BMI,NEU,LYM,MON,FBG,HDL-C,NLR,MHR,L1-4BMD,left femoral neck BMD and left hip BMD among the groups(P<0.05).Among them,NLR and MHR in the osteopenia group were higher than those in the normal bone mass group,NLR and MHR in the OP group were higher than those in the osteopenia group and the normal bone mass group,and the differences were statistically significant(P<0.05).There was no significant difference in HbAlc,TG,TC and LDL-C among the groups(P>0.05).2.Comparison of clinical data among the groups according to NLR quartileThere were statistically significant differences in NEU,LYM,FBG,HDL-C,LDL-C,NLR,MHR,L1-4BMD,left femoral neck BMD and left hip BMD among all groups(P<0.05).There was no significant difference in age,menopausal duration,course of diabetes,BMI,MON,HbA1c,TG and TC among the groups(P>0.05).3.Comparison of clinical data among the groups according to MHR quartileThere were statistically significant differences in age,menopausal duration,course of diabetes,NEU,MON,TG,HDL-C,LDL-C,NLR,MHR,L1-4BMD,Left femoral neck BMD and left hip BMD among all groups(P<0.05).There was no significant difference in BMI,LYM,FBG,HbAlc and TC among all groups(P>0.05).4.Correlation analysis between various factors and BMD of different partsSpearman rank correlation analysis showed that NLR and MHR were negatively correlated with BMD of different parts in postmenopausal T2DM patients.The correlation coefficients between NLR and L1-4BMD,left femoral neck BMD and left hip BMD were-0.329,-0.299 and-0.260,respectively.The correlation coefficients between MHR and L1-4BMD,left femoral neck BMD and left hip BMD were-0.263,-0.229 and-0.200,respectively(all P<0.05).In addition,age,menopausal duration,course of diabetes,NEU,MON and FBG were negatively correlated with L1-4BMD,left femoral neck BMD and left hip BMD(P<0.05).BMI,LYM and HDL-C were positively correlated with L1-4BMD,left femoral neck BMD and left hip BMD(P<0.05).HbAlc,TG,TC and LDL-C had no correlation with L1-4BMD,left femoral neck BMD and left hip BMD(P>0.05).5.Analysis of influencing factors of OP in postmenopausal T2DM patientsThe occurrence of OP in postmenopausal T2DM patients was used as the dependent variable,and age,menopausal duration,course of diabetes,BMI,NEU,LYM,MON,FBG,HbAlc,TG,TC,HDL-C,LDL-C,NLR and MHR were used as independent variables for univariate Logistic regression analysis.The results suggested that age,menopausal duration,course of diabetes,BMI,NEU,LYM,MON,FBG,NLR and MHR were the influencing factors of OP in postmenopausal T2DM patients.Considering the significant correlation between age and menopausal duration,MON and MHR,NEU,LYM and NLR,this study determined menopausal duration,course of diabetes,BMI,FBG,NLR and MHR as independent variables for multivariate Logistic regression analysis.The results showed that long menopausal duration[OR=1.047,95%CI(1.013,1.082)],increased NLR level[OR=1.896,95%CI(1.363,2.638)]and increased MHR level[OR=80.087,95%CI(9.138,701.883)]were independent risk factors for OP in postmenopausal T2DM patients,while increased BMI[OR=0.863,95%CI(0.794,0.938)]was an independent protective factor(all P<0.05).6.ROC curve analysis of NLR,MHR and their combination for predicting OP in postmenopausal T2DM patientsROC curve analysis showed that the area under the curve of NLR and MHR for predicting OP in postmenopausal T2DM patients was 0.666 and 0.651,the sensitivity was 57.9%and 52.6%,the specificity was 72.6%and 74.7%,and the optimal cut-off value was 2.194 and 0.374,respectively.The area under the curve of their combination was 0.774,which was higher than 0.666 and 0.651,respectively,and the differences were statistically significant(Z=3.930,P<0.001;Z=3.932,P<0.001).At this time,the maximum sensitivity was 76.3%and the specificity was 66.8%,indicating that the predictive efficiency and sensitivity of their combination would be higher.Conclusions1.With the decrease of BMD in postmenopausal T2DM patients,the levels of NLR and MHR increase gradually,and both of them are independent risk factors for OP in postmenopausal T2DM patients.2.Both NLR and MHR can be used as independent predictors of OP in postmenopausal T2DM patients,and the predictive efficiency and sensitivity of their combination would be higher.