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Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers
Objective: 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). Methods: A prospective observational study was conducted on people with T1D without diabetic peri...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486928/ https://www.ncbi.nlm.nih.gov/pubmed/37685330 http://dx.doi.org/10.3390/diagnostics13172793 |
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author | 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 |
author_facet | 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 |
author_sort | Lim, Jonathan Z. M. |
collection | PubMed |
description | Objective: 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). Methods: A prospective observational study was conducted on people with T1D without diabetic peripheral neuropathy (DPN) (n = 25), T1D with DPN (n = 28), T1D with DFU (n = 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. Results: Corneal nerve fibre length (CNFL), fibre density (CNFD) and branch density (CNBD) were lower in T1D-DPN and T1D-DFU vs. T1D (all p < 0.001). In ROC analysis, CNFD (sensitivity 88%, specificity 87%; AUC 0.93; p < 0.001; optimal cut-off 7.35 no/mm(2)) and CNFL (sensitivity 76%, specificity 77%; AUC 0.90; p < 0.001; optimal cut-off 7.01 mm/mm(2)) had good ability to differentiate T1D with and without DFU. Incident cardiovascular events (p < 0.001) and cerebrovascular events (p < 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, p = 0.01) and cerebrovascular (HR 1.55, 95% CI 1.06 to 2.26, p = 0.02) events. Conclusions: 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. |
format | Online Article Text |
id | pubmed-10486928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104869282023-09-09 Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers 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 Diagnostics (Basel) Article Objective: 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). Methods: A prospective observational study was conducted on people with T1D without diabetic peripheral neuropathy (DPN) (n = 25), T1D with DPN (n = 28), T1D with DFU (n = 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. Results: Corneal nerve fibre length (CNFL), fibre density (CNFD) and branch density (CNBD) were lower in T1D-DPN and T1D-DFU vs. T1D (all p < 0.001). In ROC analysis, CNFD (sensitivity 88%, specificity 87%; AUC 0.93; p < 0.001; optimal cut-off 7.35 no/mm(2)) and CNFL (sensitivity 76%, specificity 77%; AUC 0.90; p < 0.001; optimal cut-off 7.01 mm/mm(2)) had good ability to differentiate T1D with and without DFU. Incident cardiovascular events (p < 0.001) and cerebrovascular events (p < 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, p = 0.01) and cerebrovascular (HR 1.55, 95% CI 1.06 to 2.26, p = 0.02) events. Conclusions: 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. MDPI 2023-08-29 /pmc/articles/PMC10486928/ /pubmed/37685330 http://dx.doi.org/10.3390/diagnostics13172793 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers |
title | Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers |
title_full | Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers |
title_fullStr | Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers |
title_full_unstemmed | Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers |
title_short | Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers |
title_sort | corneal confocal microscopy predicts cardiovascular and cerebrovascular events and demonstrates greater peripheral neuropathy in patients with type 1 diabetes and foot ulcers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486928/ https://www.ncbi.nlm.nih.gov/pubmed/37685330 http://dx.doi.org/10.3390/diagnostics13172793 |
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