Cardiac Autonomic Neuropathy is Associated with Improved Diabetic Foot Ulcer Healing: A Single Centre Prospective Cohort Study

Aims People with diabetes and peripheral neuropathy (DPN) are at high risk of diabetic foot ulceration (DFU). The prevalence of cardiac autonomic neuropathy (CAN) in people with DFU is unknown and if CAN influences DFU healing is unclear. Methods We investigated, in a prospective observational single-centre cohort study, if CAN predicts DFU healing in 47 (77% male) people with a DFU and DPN attending a university hospital foot clinic. CAN was diagnosed by 2 or more abnormal Ewing's tests. Baseline DFU severity was evaluated using the site, ischaemia, neuropathy, bacterial infection, area and depth (SINBAD) score. The primary outcome was defined as evidence of DFU healing on clinical examination. Median (interquartile) length of follow-up was 1150 (624-1331) days. Results The prevalence of CAN was 43%. Of the cohort, 70% had complete healing of their DFU. Participants with CAN had a shorter median (interquartile) duration time to heal compared to those without CAN [91 (44-164) days compared to 302 (135-413) (p=0.047)]. Minor/major amputation and mortality was similar in both groups. The presence of CAN increased DFU healing by two-fold [HR=2.05, 95% CI 1.01-4.16, p=0.046] in multivariable competing risk analyses. Conclusions We demonstrate a high prevalence of CAN in a DFU cohort and that CAN is associated with improved DFU healing. The results of this study establish the scientific rationale for further studies to better understand the mechanisms between CAN and DFU outcomes.