| ObjectiveDiabetic peripheral neuropathy(DPN)is one of the most important complications of diabetes,and is an important risk factor for foot ulcers or amputation.There is no unified diagnostic criteria and method yet for DPN.Corneal confocal microscopy(CCM)is a new,simple,safe,visual,quantifiable and repeatable examination that can be used for the diagnosis of early diabetic minor nerve fiber lesions.At present,there is no discussion on corneal nerve fiber parameters of the normal population in China,and there are few domestic studies on CCM in diabetic neuropathy while most of them are small-scale studies.In this cross-sectional study,we aimed to explore the influencing factors and the range of reference values of the corneal nerve parameters in healthy adults in Jinan,and to further discuss the value of CCM in the diagnosis of diabetic neuropathy.MethodsThis study included 75 healthy-volunteers in Jinan area and 193 patients with type 2 diabetes mellitus(T2DM).Health volunteers were from permanent residents of Jinan and some of the above-mentioned families of inpatients with diabetes.Patients with type 2 diabetes received partial hospitalization from December 2015 to February 2018 at Department of Endocrinology,Qilu Hospital,Shandong University.Patients with T2DM were classified to DPN group and diabetic non-peripheral neuropathy group(NDPN)according to the diagnostic criteria for peripheral neuropathy in the"Guidelines for the prevention and treatment of diabetes(2013)" in our country.All subjects completed basic information,height,weight,glucose metabolism test,and CCM examination.All subjects completed basic information,height,weight,glucose metabolism test and CCM examination.The CCM examination was performed using the German Heidelberg laser confocal microscope and the automatic analysis software of University of Manchester(ACCMetrics).The parameters of the corneal nerve fiber were obtained:the corneal nerve fiber density(CNFD),the corneal nerve fiber branch density(CNBD)and the corneal nerve fiber length(CNFL).Patients with type 2 diabetes also underwent routine tests such as lipid metabolism and islet function,and neurological examinations such as nerve conduction velocity(NCV).Corneal nerve parameters of healthy subjects were tested for normality,and descriptive analysis was performed for each age group and the overall data.Correlation analysis was performed between corneal nerve parameters and age,gender,BMI,blood glucose,and other indicators.The normal reference value of the corneal nerve parameters was obtained.The corneal nerve parameters were further compared between the T2DM group and the healthy control group,also the DPN group and the NDPN group.The diagnostic test(fourfold table method)and the receiver operating characteristic curve(ROC)tests the diagnostic efficacy of CNFL for DPN.and draws the corresponding application subject operating characteristic curve(ROC).All data were analyzed by SPSS 19.0 software,and P<0.005 showed statistically significant difference.Results1.There were 75 healthy volunteers,including 28 males(37.3%)and 47 females(62.7%).CNFD,CNBD and CNFL applied the Shapiro-Wilk method to normality tests respectively,and plotted the corresponding QQ graphs.The results showed that all the parameters were from the normal distributed population.2.The average levels of CNFD,CNBD,and CNFL were 28.31 ±6.92 no./mm~2,47.18+25.92 no./mm~2,and 18.51 ±2.93 mm/mm~2,respectively.The chi-square test found no statistical differences between the gender groups.The correlations between CNFD,CNFL,and CNBD with age,sex,BMI,systolic blood pressure,diastolic blood pressure,HbAlc,and FBG were performed by Pearson correlation analysis.Results showed that there were no significant correlations between corneal nerve fiber parameters and the above indicators.3.The 95%normal reference ranges for CNFD,CNBD,and CNFL are>16.94 no./mm~2,>4.54 no./mm~2,and>13.69 mm/mm~2,respectively.4.The mean levels of CNFD,CNBD and CNFL in the T2DM group and the healthy control group were 21.96±8.07 no./mm~2 and 28.56±6.90 no./mm~2,35.60±123.04 no./mm~2 and 49.27±25.27no./mm~2,15.07±3.86 mm./mm~2 and 18.59±13.27mm/mm~2.All parameters were significantly lower in the T2DM group compared with the healthy control group,and the difference was statistically significant.5.The mean levels of CNFD,CNBD and CNFL in the DPN group and the NDPN group were 19.61 ±6.81 no./mm~2 and 26.48±8.42 no./Imm~2,28.49±18.44 no./mm~2 and 49.27±25.03 no./mm~2,13.89±3.26 mm./mm~2 and 17.34±3.94mm/mm~2.All parameters were significantly lower in the DPN group than in the NDPN group,and the difference was statistically signifiicant6.The Pearson correlation analysis of the parameters of corneal nerve fibers in the diabetic group and the nerve conduction velocity respectively was underwent.Results found that there was a positive correlation between CNFD and the left median nerve conduction velocity(r=0.171),the left/right radial nerve transmission speed(r=0.202,r=171),mean nerve conduction velocity in upper/lower limbs(r=0.167,r=0.214).There was a positive correlation between CNBD and left/right median nerve conduction velocity(r=0.259,r=0.190),left/right radial nerve conduction velocity(r=0.177,r=0.154),and the mean conduction velocity of upper/lower limbs(r=0.254,r=0.190).There was a positive correlation between CNFL and left/right median nerve(r=0.178,r=0.162)and the average conduction velocity of upper limbs(r=0.192).All P values less than 0.005.7.According to the Diagnostic Criteria for Diabetic Peripheral Neuropathy in the Guidelines for the Prevention and Treatment of Diabetes in 2013 in China,the diagnostic value by fourfold table with CNFL>13.69 mm/mm~2 was found with sensitivity of 48.8%,specificity of 78.8%.At the same time,the ROC curves for CNFD,CNBD,and CNFL were plotted with the area under the curve(AUI)of 0.736(95%CI 0.661?0.811),0.754(95%CI 0.682?0.827),and 0.741(95%CI 0.663?0.818).According to the ROC curve,CNFL was determined the best cut-point value of 16.98mm/mm~2 with the sensitivity of 81.9%and the specificity of 56.1%.8.Correlative analysis of corneal nerve fiber parameters and clinical indicators found that CNFD was negatively correlated with age and duration of disease,and positively correlated with uric acid;CNBD was positively correlated with uric acid,cystatin-c and HOMA-P;CNFL was negatively correlated with disease duration and HbAlc,while was positively correlated with uric acid.Conclusions1.In healthy adults,corneal nerve fiber parameters are normally distributed,and there is no significant correlation between these parameters and age,gender,BMI,and blood glucose levels.The normal reference ranges for CNFD,CNBD,and CNFL in Jinan are>16.94 no./mm~2,>4.54 no./mm~2 and>13.69 mm/mm~2.CNFL is more stable than CNFD?CNBD.2.Compared with people with normal blood glucose,corneal nerve fiber parameters decreased significantly in patients with diabetes.When diabetic patients are with peripheral neuropathy,corneal nerve fiber parameters decreased significantly.3.Confocal microscopy is a rapid,noninvasive,repeatable and quantifiable new method.It has a certain diagnostic value for diabetic peripheral neuropathy.CNFL is recommended within the three parameters,and the cut-point value is 13.69 mm./mm~2. |
PDF Full Text Request