Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers
Jonathan Z. M. Lim,
Jamie Burgess,
Cheong Ooi,
Maryam Ferdousi,
Shazli Azmi,
Alise Kalteniece,
Matthew Anson,
Daniel J. Cuthbertson,
Ioannis N. Petropoulos,
Rayaz A. Malik,
John P. H. Wilding,
Uazman Alam
Affiliations
Jonathan Z. M. Lim
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
Jamie Burgess
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
Cheong Ooi
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
Maryam Ferdousi
Institute of Cardiovascular Sciences, Cardiac Centre, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester M13 9WL, UK
Shazli Azmi
Diabetes, Endocrinology, and Metabolism Centre, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK
Alise Kalteniece
Institute of Cardiovascular Sciences, Cardiac Centre, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester M13 9WL, UK
Matthew Anson
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
Daniel J. Cuthbertson
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
Ioannis N. Petropoulos
Department of Medicine, Weill Cornell Medicine-Qatar, Doha P.O. Box 24144, Qatar
Rayaz A. Malik
Department of Medicine, Weill Cornell Medicine-Qatar, Doha P.O. Box 24144, Qatar
John P. H. Wilding
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
Uazman Alam
Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK
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 p 2) and CNFL (sensitivity 76%, specificity 77%; AUC 0.90; p 2) had good ability to differentiate T1D with and without DFU. Incident cardiovascular events (p p 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.
