| ObjectiveThe purpose of present study is to observe the changes of bone metabolic markers,bone mineral density(BMD)and fracture risk in type 2 diabetes mellitus(T2DM)patients with cardiac autonomic neuropathy(CAN),investigating the correlation between CAN and BMD and fracture risk in T2 DM patients,so as to provide new ideas for the early prediction of osteoporosis in T2 DM patients with CAN.MethodsA total of 278 patients with T2 DM who were admitted to the Department of Endocrinology,the First Hospital of Lanzhou University from July 2021 to July 2022 and met the inclusion and exclusion criteria were enrolled.According to the Cardiovascular Autonomic Reflex Tests(CARTs),the patients were divided into CAN(+)and CAN(-)groups,including 118 patients in CAN(+)group and 160 patients in CAN(-)group.The clinical data and laboratory indicators of the subjects were collected in detail.Heart rate variability(HRV)was analyzed by 24-hour dynamic electrocardiogram.BMD of hip,lumbar spine and femoral neck was measured by Lunar dual-energy X-ray absorptiometry.Fracture risk assessment tool(FRAX)was used to assess the 10-year risk of major osteoporotic fracture(MOF)and hip fracture(HF1).The differences of basic clinical data,bone metabolism markers,BMD and fracture risk between CAN(+)and CAN(-)groups were compared.The proportion of different bone mass in T2 DM patients with different degrees of CAN was analyzed.According to different body mass index(BMI),patients were divided into four groups,and the differences of bone metabolism markers,BMD and fracture risk among groups were compared.According to different bone mass,T2 DM patients with CAN were divided into three groups: normal bone mass,decreased bone mass and osteoporosis,and the differences of HRV parameters among the three groups were compared.Spearman correlation analysis was used to explore the correlations between HRV parameters and bone metabolism indexes,BMD,fracture risk in T2 DM patients with CAN.Multiple linear regression was conducted to analyze the risk factors of decreased BMD and increased fracture risk.In addition,receiver operating characteristic curve(ROC)was used to analyze the optimal cut-off value of HRV parameter LF/HF ratio for screening osteoporosis in T2 DM patients with CAN.SPSS25.0 software was used to analyze the data.Results1.Comparison of basic clinical data,bone metabolic markers,BMD and fracture risk between two groupsCompared with CAN(-)group,the duration of diabetes,Hb Alc and resting heart rate were significantly increased,while 25(OH)D was significantly decreased(P <0.05)in CAN(+)group.There was no significant difference in history of fragility fracture between two groups.Compared with CAN(-)group,BMD of hip,lumbar spine,and femoral neck were significantly lower(P < 0.05),while fracture risk(including MOF and HF1)were significantly higher(P < 0.05)in CAN(+)group.There were no statistically significant differences in other clinical data and laboratory parameters(P > 0.05).2.The proportion of different bone mass in T2 DM patients with different degrees of CANAccording to different bone mass,the patients were divided into normal bone mass,osteopenia and osteoporosis.The proportion of different bone mass in patients with different degrees of CAN was statistically analyzed.The results showed that there were 91 patients in ACAN group,in which 41 patients with normal bone mass,accounting for 45.0%,and 15 patients with osteoporosis,accounting for 16.5%.With the increase of CAN severity,the proportion of patients with normal bone mass gradually decreased,while the proportion of patients with osteoporosis gradually increased.Among 70 patients in ACAN group,12 patients had normal bone mass,accounting for 17.1%,and the number of osteoporosis was 37,accounting for about52.9%.Compared with NCAN group,the number of osteoporosis in ACAN group was significantly higher.3.Comparison of bone metabolic markers,BMD and fracture risk in T2 DM patients with CAN with different BMI(1)Comparison of bone metabolic markers in T2 DM patients with CAN with different BMI: The results showed that 25(OH)D,OC,β-CTX and P1 NP showed a decreasing trend with the increase of BMI.Compared with low weight group and normal weight group,the levels of 25(OH)D and β-CTX in obese group were significantly decreased,and the difference was statistically significant(P < 0.05).The level of β-CTX in overweight patients was significantly lower than that in low weight group and normal weight group(P < 0.05).There was no significant difference in other bone metabolism markers among groups(P > 0.05).(2)Comparison of BMD and fracture risk in T2 DM patients with CAN with different BMI: with the increase of BMI,BMD of hip,lumbar spine and femoral neck showed an increasing trend.Compared with patients in low weight and normal weight groups,BMD of the hip,lumbar spine and femoral neck were significantly increased in obese group,and the difference was statistically significant(P < 0.05).Compared with overweight patients,hip BMD in obesity group was significantly increased(P <0.05).MOF showed an increasing trend with the increase of BMI,while there was no significant difference among groups(P = 0.061).HF1 decreased with the increase of BMI.Compared with low weight group,HF1 was significantly decreased in overweight and obese groups(P < 0.05).4.Comparison of HRV parameters in T2 DM patients with CAN with different bone massAccording to different bone mass,118 patients in CAN(+)group were divided into three groups: normal bone mass,decreased bone mass and osteoporosis,and HRV parameters of the three groups were analyzed.The results showed that with decrease of bone mass,LF/HF ratio was gradually increased,while the other parameters of HRV decreased with the decline of bone mass.In HRV frequency domain analysis parameters,HF in osteoporosis group was significantly lower than that in normal bone mass group(P < 0.05).There was no significant difference in TP,VLF and LF between the two groups(P > 0.05).In HRV time domain analysis parameters,r MSSD and p NN50 in osteoporosis group were significantly lower than those in normal bone mass group(P < 0.05).There was no significant difference in SDNN and SDANN among three groups(P > 0.05).5.Spearman correlation analysis of bone metabolic markers,BMD,fracture risk and HRV parameters in T2 DM patients with CAN(1)Spearman correlation analysis of bone metabolic markers and HRV parameters in T2 DM patients with CAN: 25(OH)D was positively correlated with HF,r MSSD and p NN50(P < 0.05),while negatively correlated with LF/HF ratio(P <0.05).β-CTX level was negatively correlated with HF(P < 0.05),while positively correlated with LF/HF ratio(P < 0.05).(2)Spearman correlation analysis of BMD,fracture risk and HRV parameters in T2 DM patients with CAN: HF was positively correlated with BMD of hip,lumbar spine and femoral neck(P < 0.05),while negatively correlated with MOF and HF1(P< 0.05).LF/HF ratio was negatively correlated with BMD of hip,lumbar spine and femoral neck(P < 0.05),while positively correlated with MOF and HF1(P < 0.05).There were significant positive correlation between r MSSD and BMD of hip and lumbar,but no significant correlation between r MSSD and femoral neck BMD,MOF and HF1.p NN50 was positively correlated with hip BMD,while there were no significantly correlation with lumbar BMD,femoral neck BMD,MOF and HF1.6.Multiple linear regression analysis of BMD and fracture risk in T2 DM patients with CANThe decreased BMD of hip,lumbar spine and femoral neck in T2 DM patients with CAN is associated with longer duration of diabetes,higher LF/HF ratio,lower HF and lower 25(OH)D.Increased MOF and HF1 are associated with lower HF and higher LF/HF ratio in T2 DM patients with CAN.In addition,compared with men,female is not only a risk factor for decreased hip BMD,but also a risk factor for increased fracture risk in T2 DM patients.After gradual adjustment for multiple risk factors,the result showed that increased LF/HF ratio was still an independent risk factor for decreased BMD and increased fracture risk.7.ROC curve analysis of LF/HF ratio screening osteoporosisAccording to the ROC curve analysis results,the AUC of LF/HF ratio for screening osteoporosis in T2 DM patients with CAN was 0.877(95%CI:0.803-0.950,P<0.001).The LF/HF ration level of 3.185 was the best cut-off value for screening osteoporosis in T2 DM patients with CAN,with a sensitivity of 85.7% and a specificity of 86.7%.Conclusions:CAN is associated with decreased BMD of hip,lumbar spine and femoral neck and increased fracture risk in patients with T2 DM.The more severe the CAN lesions,the decrease of BMD and the increase of fracture risk were more obvious.CAN has a certain predictive value for the occurrence of diabetic osteoporosis in T2 DM.Decreased HF and increased LF/HF ratio were associated with decreased BMD of hip,lumbar spine and femoral neck and increased fracture risk in T2 DM patients with CAN.High LF/HF ratio is an independent risk factor for decreased BMD of hip,lumbar spine and femoral neck and increased fracture risk.LF/HF ratio may be used as predictors of osteoporosis,and have certain clinical value in predicting the occurrence of early osteoporosis in T2 DM patients with CAN. |
