Bruce A Perkins1,2, Leif Erik Lovblom3, Evan J H Lewis3, Vera Bril4, Maryam Ferdousi5, Andrej Orszag3, Katie Edwards6, Nicola Pritchard6, Anthony Russell7, Cirous Dehghani6, Danièle Pacaud8, Kenneth Romanchuk8, Jean K Mah8, Maria Jeziorska5, Andrew Marshall8, Roni M Shtein9, Rodica Pop-Busui9, Stephen I Lentz9, Mitra Tavakoli5,10, Andrew J M Boulton5, Nathan Efron6, Rayaz A Malik5,11. 1. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada bruce.perkins@sinaihealth.ca. 2. Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 3. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 4. The Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Krembil Neuroscience Centre, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada. 5. University of Manchester, Manchester, U.K. 6. Queensland University of Technology, Brisbane, Queensland, Australia. 7. University of Queensland, Woolloongabba, Queensland, Australia. 8. Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada. 9. University of Michigan, Ann Arbor, MI. 10. Diabetes and Vascular Research Centre, NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K. 11. Weill Cornell Medicine-Qatar, Doha, Qatar.
Abstract
OBJECTIVE: Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN. RESEARCH DESIGN AND METHODS: From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN. The predictive validity of CNFL for the development of DPN was determined using time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 203 participants had type 1 and 58 had type 2 diabetes. Mean follow-up time was 5.8 years (interquartile range 4.2-7.0). New-onset DPN occurred in 60 participants (23%; 4.29 events per 100 person-years). Participants who developed DPN were older and had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and corneal confocal microscopy parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve for CNFL ranged between 0.61 and 0.69 for years 1-5 and was 0.80 at year 6. The optimal diagnostic threshold for a baseline CNFL of 14.1 mm/mm2 was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70-5.11; P < 0.001) for new-onset DPN. CONCLUSIONS: CNFL showed good predictive validity for identifying patients at higher risk of developing DPN ∼6 years in the future.
OBJECTIVE: Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN. RESEARCH DESIGN AND METHODS: From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN. The predictive validity of CNFL for the development of DPN was determined using time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 203 participants had type 1 and 58 had type 2 diabetes. Mean follow-up time was 5.8 years (interquartile range 4.2-7.0). New-onset DPN occurred in 60 participants (23%; 4.29 events per 100 person-years). Participants who developed DPN were older and had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and corneal confocal microscopy parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve for CNFL ranged between 0.61 and 0.69 for years 1-5 and was 0.80 at year 6. The optimal diagnostic threshold for a baseline CNFL of 14.1 mm/mm2 was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70-5.11; P < 0.001) for new-onset DPN. CONCLUSIONS: CNFL showed good predictive validity for identifying patients at higher risk of developing DPN ∼6 years in the future.
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