title: In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes.
abstract: OBJECTIVE
  To investigate whether small nerve fibre degeneration detected using corneal confocal microscopy is associated with cardiac autonomic neuropathy in people with Type 1 diabetes.
  
  
  METHODS
  Thirty-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.
  
  
  RESULTS
  Compared with control participants, participants with Type 1 diabetes had fewer (mean ± SD 45.4 ± 20.2 vs 92.0 ± 22.7 fibres/mm²; 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 (mean ± SD 15.1 ± 3.5 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 ± 18.9 fibres/mm²; 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).
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Endocrinology and Diabetes, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maddaloni
authors.forename: F
authors.initials: F
authors.lastname: Sabatino
authors.forename: R
authors.initials: R
authors.lastname: Del Toro
authors.forename: S
authors.initials: S
authors.lastname: Crugliano
authors.forename: S
authors.initials: S
authors.lastname: Grande
authors.forename: A
authors.initials: A
authors.lastname: Lauria Pantano
authors.forename: A R
authors.initials: AR
authors.lastname: Maurizi
authors.forename: A
authors.initials: A
authors.lastname: Palermo
authors.forename: S
authors.initials: S
authors.lastname: Bonini
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
authors.forename: S
authors.initials: S
authors.lastname: Manfrini
mesh_terms: D000328:Adult; D017776:Autonomic Pathways / Q000473:pathology / Q000503:physiopathology; D003315:Cornea / Q000294:innervation / Q000473:pathology*; D003316:Corneal Diseases / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy; D058065:Diabetic Cardiomyopathies / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D003943:Diagnostic Techniques, Neurological / Q000009:adverse effects / Q000295:instrumentation; D003941:Diagnostic Techniques, Ophthalmological / Q000009:adverse effects / Q000295:instrumentation; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D009412:Nerve Fibers / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin