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

Diabet Med. 2015 Feb;32(2):262-6. doi: 10.1111/dme.12583. Epub 2014 Sep 24.

Abstract

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.

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).

Conclusion: 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.

MeSH terms

  • Adult
  • Autonomic Pathways / pathology
  • Autonomic Pathways / physiopathology
  • Cornea / innervation
  • Cornea / pathology*
  • Corneal Diseases / complications
  • Corneal Diseases / diagnosis*
  • Corneal Diseases / pathology
  • Corneal Diseases / physiopathology
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetic Cardiomyopathies / complications
  • Diabetic Cardiomyopathies / diagnosis*
  • Diabetic Cardiomyopathies / pathology
  • Diabetic Cardiomyopathies / physiopathology
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / diagnosis*
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology
  • Diagnostic Techniques, Neurological / adverse effects
  • Diagnostic Techniques, Neurological / instrumentation
  • Diagnostic Techniques, Ophthalmological / adverse effects
  • Diagnostic Techniques, Ophthalmological / instrumentation
  • Early Diagnosis
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / therapeutic use
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Nerve Degeneration / complications
  • Nerve Degeneration / diagnosis*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Nerve Fibers / pathology
  • Severity of Illness Index

Substances

  • Hypoglycemic Agents
  • Insulin