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

Abstract

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.

Key words

cardiac autonomic neuropathy - diabetes - diabetic foot ulcer

• Reference

• 1 Vinik AI, Casellini C, Parson HK. et al. Cardiac autonomic neuropathy in diabetes: A predictor of cardiometabolic events. Front Neurosci 2018; 12: 591
• 2 Yun J, Cha S, Lim T. et al Cardiovascular autonomic dysfunction predicts diabetic foot ulcers in patients with type 2 diabetes without diabetic polyneuropathy. Medicine 2016; 95: e3128
• 3 Menon A, Dixit A, Garg M. et al. Cardiac autonomic neuropathy in patients with Type 2 diabetes mellitus at high risk for foot ulcers. Indian J Endocr Metab 2017; 21: 282-285
• 4 Ewing DJ, Campbell IW, Clarke BF. Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. Ann Intern Med 1980; 92 (2 Pt 2) 308-311
• 5 Spallone V, Ziegler D, Freeman R. et al. Cardiovascular autonomic neuropathy in diabetes: Clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 2011; 27: 639-653
• 6 Ince P, Abbas Z, Lutale J. et al. Use of the SINBAD classification system and score in comparing outcome of foot ulcer management on three continents. Diabetes Care. 2008; 31: 964-967
• 7 Jeffcoate WJ, Bus SA, Game FL. et al. Reporting standards of studies and papers on the prevention and management of foot ulcers in diabetes: Required details and markers of good quality. Lancet Diabetes Endocrinol 2016; 4: 781-788
• 8 Vinik A, Erbas T, Casellini C. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Investig 2013; 4: 4-18 https://doi.org/10.1111/jdi.12042
• 9 Bus S, Armstrong D, van Deursen R. et al. IWGDF guidance on footwear and offloading interventions to prevent and heal foot ulcers in patients with diabetes. Diabetes Metab Res Rev 2016; 32: 25-36
• 10 Matta M, Pavy-Le Traon A, Perez-Lloret S. et al Predictors of cardiovascular autonomic neuropathy onset and progression in a cohort of type 1 diabetic patients. J Diabetes Res 2018; 2018: 1-8