角膜共焦显微镜对于糖尿病自主神经病变的早期诊断价值

Early diagnosis of diabetic autonomic neuropathy by corneal confocal microscopy

目的 通过角膜共焦显微镜观察糖代谢异常伴有自主神经病变患者的角膜神经改变,评价其对于糖代谢异常患者自主神经病变的早期诊断价值.方法 来自2014年1-8月北京大学第三医院内分泌科、神经内科门诊和住院糖耐量异常（IGT）和新发糖尿病患者50例,根据心血管自主功能（CAF）检查结果分为自主神经病变患者20例和非自主神经病变患者30例,同时纳入年龄性别匹配的正常对照组50名,采用角膜共焦显微镜（CCM）观察记录并量化分析角膜上皮下神经纤维形态,同时进行自主神经症状量表（SAS）,皮肤交感反射（SSR）,接触性热痛诱发电位（CHEP）等检查.结果 t检验显示与糖代谢异常非自主神经病变患者组比较,糖代谢异常自主神经病变患者组神经纤维长度（NFL）减少[分别为（15±5）,（13±5） mm/mm2],但差异无统计学意义（￡=1.275,P=0.232）、角膜神经纤维密度（NFD）、神经分支密度（NBD）均显著减少,神经曲折度（NFT）进一步增加,差异有统计学意义（t=10.17、4.81、7.78,P=0.002、0.031、0.003）.Pearson相关分析SAS评分与NFT,NFD,NFL相关（r=0.628,-0.304、-0.217,P＜0.001、P=0.002、0.03）;角膜共焦显微镜观察结果四项指标中神经曲折度与自主神经病变严重程度关系最为密切.结论 角膜共焦显微镜作为一种无创新型敏感的检测手段,对于糖代谢异常自主神经病变的早期诊断有重要价值.

Objective To investigate the early diagnostic value of corneal confocal microscopy by observing corneal innervation alteration in patients with autonomic neuropathy with impaired glucose tolerance.Methods A total of 50 subjects with neuropathy with impaired glucose tolerance or newly diagnosed type 2 diabetes,including 20 subjects with diabetic autonomic neuropathy （AN） and 30 subjects with non-autonomic neuropathy （NAN） according to the result of cardiovascular autonomic function test,and 50 aged-matched control subjects were included in this study.All the subjects came from the Department of Neurology and Endocrine from Jan to Aug 2014,and underwent a detailed evaluation of neuropathic symptoms,corneal confocal microscopy,the Survey of Autonomic Symptoms,sympathetic skin response and contact heat evoked potential test.Results T test indicated patients with AN had significant reductions in nerve branch density （NBD） and nerve fiber density （NFD）,and increase in corneal nerve fiber tortuosity （NFT） compared with the NAN patients （t =10.17,4.81,7.78;P =0.002,0.031,0.003）.Though corneal nerve fiber length （NFL） decreased （（15 ± 5） vs （13 ± 5） mm/mm2）,there is no statistic significance （t =1.275,P =0.232）.Pearson＇ s correlation analysis showed the severity of autonomic neuropathy significantly correlated with cornea nerves damage.The Survey of Autonomic Symptoms （SAS） significantly correlated with NFT,NFD,NFL （r =0.628,-0.304,-0.217;P 〈 0.001,P =0.002,0.03）.NFT was the most significant determinant for the severity of autonomic neuropathy among the four observed parameters.Conclusion Corneal confocal microscopy provides a new sensitive non-invasive means to detect autonomic nerve fiber damage in patients with impaired glucose tolerance and would be of value in assessing neuropathic autonomic symptoms in clinical practice and epidemiologic studies.