In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes

Aims: To investigate whether small nerve fibre degeneration detected using corneal confocal microscopy is associated with cardiac autonomic neuropathy in people with Type 1 diabetes. MethodsThirty-six people with Type 1 diabetes and 20 age- and sex-matched healthy control subjects were enrolled. Tests to determine heart rate response to deep-breathing (expiratory-to-inspiratory ratio), heart rate response to lying-to-stand 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. ResultsCompared with control participants, participants with Type 1 diabetes had fewer (meansd 45.420.2 vs 92.022.7fibres/mm(2); P<0.001) and more tortuous corneal nerve fibres (20 participants with Type 1 diabetes vs four control participants had nerve tortuosity grade 2/3; P=0.022) and fewer beadings (meansd 15.13.5 vs 20.6 +/- 5.0; P<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 +/- sd 32.8 +/- 16.4 vs 51.7 +/- 18.9fibres/mm(2); P=0.008). This difference remained significant after adjustment for age (P=0.02), gender (P=0.04), disease duration (P=0.005), insulin requirement (P=0.02) and neuropathy disability score (P=0.04). ConclusionThis study suggests that corneal confocal microscopy could represent a new and non-invasive 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.