{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:37:22Z","timestamp":1789983442672,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T00:00:00Z","timestamp":1411516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet. Med."],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate whether small nerve fibre degeneration detected using corneal confocal microscopy is associated with cardiac autonomic neuropathy in people with Type 1 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010six people with Type 1 diabetes and 20 age\u2010 and sex\u2010matched healthy control subjects were enrolled. Tests to determine heart rate response to deep\u2010breathing (expiratory\u2010to\u2010inspiratory ratio), heart rate response to lying\u2010to\u2010stand test (30:15 ratio) and blood pressure response to standing were performed to detect cardiac autonomic neuropathy. Corneal confocal microscopy was performed to assess: corneal nerve density and corneal nerve beadings; branching pattern; and nerve fibre tortuosity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with control participants, participants with Type 1 diabetes had fewer (mean\u00a0\u00b1\u00a0<jats:sc>sd<\/jats:sc> 45.4\u00a0\u00b1\u00a020.2 vs 92.0\u00a0\u00b1\u00a022.7\u00a0fibres\/mm<jats:sup>2<\/jats:sup>; <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.001) and more tortuous corneal nerve fibres (20 participants with Type 1 diabetes vs four control participants had nerve tortuosity grade 2\/3; <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.022) and fewer beadings (mean\u00a0\u00b1\u00a0<jats:sc>sd<\/jats:sc> 15.1\u00a0\u00b1\u00a03.5 vs 20.6\u00a0\u00b1\u00a05.0; <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.001). Of the participants with Type 1 diabetes, 11 met the criteria for the diagnosis of cardiac autonomic neuropathy. Corneal nerve density was significantly lower in participants with cardiac autonomic neuropathy than in those without (mean\u00a0\u00b1\u00a0<jats:sc>sd<\/jats:sc> 32.8\u00a0\u00b1\u00a016.4 vs 51.7\u00a0\u00b1\u00a018.9\u00a0fibres\/mm<jats:sup>2<\/jats:sup>; <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.008). This difference remained significant after adjustment for age (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.02), gender (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.04), disease duration (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.005), insulin requirement (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.02) and neuropathy disability score (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study suggests that corneal confocal microscopy could represent a new and non\u2010invasive tool to investigate cardiac autonomic neuropathy in people with Type 1 diabetes. Larger studies are required to define the role of corneal confocal microscopy in the assessment of cardiac autonomic neuropathy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12583","type":"journal-article","created":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T15:18:48Z","timestamp":1409757528000},"page":"262-266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["<i>In vivo<\/i> corneal confocal microscopy as a novel non\u2010invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes"],"prefix":"10.1111","volume":"32","author":[{"given":"E.","family":"Maddaloni","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sabatino","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Del Toro","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Crugliano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Grande","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lauria Pantano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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