Corneal confocal microscopy and cardiac autonomic neuropathy in individuals with type 1 diabetes mellitus

BACKGROUND AND AIMS: Cardiac autonomic neuropathy (CAN) in diabetes is associated with increased mortality. Corneal confocal microscopy (CCM) is a non-invasive imaging modality that quantifies small fiber neuropathy. The aim of this study was to examine the association between CCM-derived corneal nerve parameters and CAN in individuals with type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional study included individuals with T1DM and age-matched non-diabetic controls. CAN was diagnosed using the gold standard Ewing cardiovascular autonomic reflex tests and participants with T1DM were classified into CAN and non-CAN groups. All participants underwent CCM to assess corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL). RESULTS: A total of 146 participants were included (94 with T1DM and 52 controls). Among participants with T1DM, 33 (35.1%) had CAN. Participants with CAN were older and had a longer duration of diabetes than those without CAN. In univariate analyses, CNFL was associated with age, body mass index (BMI), hypertension, estimated glomerular filtration rate (eGFR), presence of CAN, CAN score, and multiple autonomic and peripheral neuropathy measures. In multivariable analysis after adjusting for age, diabetes duration, hypertension, peripheral neuropathy and eGFR, higher BMI (β = -0.285, p = 0.028) and presence of CAN (β = -0.279, p = 0.040) remained independently associated with lower CNFL. CONCLUSION: In individuals with T1DM, the presence of CAN and higher BMI were independently associated with reduced CNFL. These findings indicate an association between corneal small-fiber pathology and autonomic dysfunction in T1DM, supporting the role of CCM as a non-invasive measure of neuropathy burden, while longitudinal studies are required to determine its diagnostic or prognostic utility.