Lim Jonathan Z M, Burgess Jamie, Ooi Cheong, Ferdousi Maryam, Azmi Shazli, Kalteniece Alise, Anson Matthew, Cuthbertson Daniel J, Petropoulos Ioannis N, Malik Rayaz A, Wilding John P H, Alam Uazman
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK.
Diabetes, Endocrinology, and Metabolism Centre, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
Diagnostics (Basel). 2023 Aug 29;13(17):2793. doi: 10.3390/diagnostics13172793.
In this study, we evaluate small and large nerve fibre pathology in relation to diabetic foot ulceration (DFU) and incident cardiovascular and cerebrovascular events in type 1 diabetes (T1D).
A prospective observational study was conducted on people with T1D without diabetic peripheral neuropathy (DPN) ( = 25), T1D with DPN ( = 28), T1D with DFU ( = 25) and 32 healthy volunteers. ROC analysis of parameters was conducted to diagnose DPN and DFU, and multivariate Cox regression analysis was performed to evaluate the predictive ability of corneal nerves for cardiac and cerebrovascular events over 3 years.
Corneal nerve fibre length (CNFL), fibre density (CNFD) and branch density (CNBD) were lower in T1D-DPN and T1D-DFU vs. T1D (all < 0.001). In ROC analysis, CNFD (sensitivity 88%, specificity 87%; AUC 0.93; < 0.001; optimal cut-off 7.35 no/mm) and CNFL (sensitivity 76%, specificity 77%; AUC 0.90; < 0.001; optimal cut-off 7.01 mm/mm) had good ability to differentiate T1D with and without DFU. Incident cardiovascular events ( < 0.001) and cerebrovascular events ( < 0.001) were significantly higher in T1D-DPN and T1D-DFU. Corneal nerve loss, specifically CNFD predicted incident cardiovascular (HR 1.67, 95% CI 1.12 to 2.50, = 0.01) and cerebrovascular (HR 1.55, 95% CI 1.06 to 2.26, = 0.02) events.
Our study provides threshold values for corneal nerve fibre metrics for neuropathic foot at risk of DFU and further demonstrates that lower CNFD predicts incident cardiovascular and cerebrovascular events in T1D.
在本研究中，我们评估了1型糖尿病（T1D）中小神经纤维和大神经纤维病变与糖尿病足溃疡（DFU）以及心血管和脑血管事件发生的关系。
对无糖尿病周围神经病变（DPN）的T1D患者（n = 25）、患有DPN的T1D患者（n = 28）、患有DFU的T1D患者（n = 25）以及32名健康志愿者进行了一项前瞻性观察研究。对各项参数进行ROC分析以诊断DPN和DFU，并进行多变量Cox回归分析以评估角膜神经在3年内对心脏和脑血管事件的预测能力。
与T1D患者相比，T1D-DPN和T1D-DFU患者的角膜神经纤维长度（CNFL）、纤维密度（CNFD）和分支密度（CNBD）较低（均P < 0.001）。在ROC分析中，CNFD（敏感性88%，特异性87%；AUC 0.93；P < 0.001；最佳截断值7.35条/mm）和CNFL（敏感性76%，特异性77%；AUC 0.90；P < 0.001；最佳截断值7.01mm/mm）具有良好的区分有无DFU的T1D患者的能力。T1D-DPN和T1D-DFU患者的心血管事件发生率（P < 0.001）和脑血管事件发生率（P < 0.001）显著更高。角膜神经损伤，特别是CNFD可预测心血管事件（HR 1.67，95%CI 1.12至2.50，P = 0.01）和脑血管事件（HR 1.55，95%CI 1.06至2.26，P = 0.02）的发生。
我们的研究提供了有DFU风险的神经性足部角膜神经纤维指标的阈值，并进一步证明较低的CNFD可预测T1D患者心血管和脑血管事件的发生。
