INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.

2nd Faculty of Medicine Department of Cardiology Motol University Hospital Charles University Prague Czech Republic

2nd Faculty of Medicine Department of Internal Medicine Motol University Hospital Charles University Prague Czech Republic

2nd Faculty of Medicine Department of Neurology Motol University Hospital Charles University Prague Czech Republic

Faculty of Biomedical Engineering Czech Technical University Prague Prague Czech Republic

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Astrup, A. S. , Tarnow, L. , Rossing, P. , Hansen, B. V. , Hilsted, J. , & Parving, H. H. (2006). Cardiac autonomic neuropathy predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy. Diabetes Care, 29(2), 334–339. 10.2337/diacare.29.02.06.dc05-1242 PubMed DOI

Azmi, S. , Petropoulos, I. N. , Ferdousi, M. , Ponirakis, G. , Alam, U. , & Malik, R. A. (2019). An update on the diagnosis and treatment of diabetic somatic and autonomic neuropathy. F1000Research, 8, 186. 10.12688/f1000research.17118.1 ] PubMed DOI PMC

Barbosa, M. , Saavedra, A. , Severo, M. , Maier, C. , & Carvalho, D. (2017). Validation and Reliability of the Portuguese Version of the Michigan Neuropathy Screening Instrument. Pain Practice: The Official Journal of World Institute of Pain, 17(4), 514–521. 10.1111/papr.12479 PubMed DOI

Boulton, A. J. M. , Vinik, A. I. , Arezzo, J. C. , Bril, V. , Feldman, E. L. , Freeman, R. , Malik, R. A. , Maser, R. E. , Sosenko, J. M. , Ziegler, D. , & American Diabetes Association. (2005). Diabetic neuropathies: A statement by the American Diabetes Association. Diabetes Care, 28, 956–962. 10.2337/diacare.28.4.956 PubMed DOI

Dyck, P. J. , Zimmerman, I. R. , O’ Brien, P. C. , Ness, A. , Caskey, P. E. , Karnes, J. , & Bushek, W. (1978). Introduction of automated systems to evaluate touch‐pressure, vibration, and thermal cutaneous sensation in man. Annals of Neurology, 4, 502–510. 10.1002/ana.410040605 PubMed DOI

Freynhagen, R. , Baron, R. , Gockel, U. , & Tölle, T. R. (2006). painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain. Current Medical Research and Opinion, 22, 1911–1920. 10.1185/030079906X132488 PubMed DOI

Fruhstorfer, H. , Lindblom, U. , & Schmidt, W. G. (1976). Method for quantitative estimation of thermal thresholds in patients. Journal of Neurology, Neurosurgery and Psychiatry, 39, 1071–1075. 10.1136/jnnp.39.11.1071 PubMed DOI PMC

Herman, W. H. , Pop‐Busui, R. , Braffett, B. H. , Martin, C. L. , Cleary, P. A. , Albers, J. W. , Feldman, E. L. , & DCCT/EDIC Research Group. (2012). Use of the Michigan neuropathy screening instrument as a measure of distal symmetrical peripheral neuropathy in type1 diabetes: Results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications. Diabetic Medicine, 29, 937–944. 10.1111/j.1464-5491.2012.03644.x PubMed DOI PMC

Islam, S. K. M. A. , Kim, D. , Lee, Y. S. , & Moon, S. S. (2018). Association between diabetic peripheral neuropathy and heart rate variability in subjects with type 2 diabetes. Diabetes Research and Clinical Practice, 140, 18–26. 10.1016/j.diabres.2018.03.034 PubMed DOI

Low, P. A. , Benrud‐Larson, L. M. , Sletten, D. M. , Opfer‐Gehrking, T. L. , Weigand, S. D. , O'Brien, P. C. , Suarez, G. A. , & Dyck, P. J. (2004). Autonomic symptoms and diabetic neuropathy: A population‐based study. Diabetes Care, 27(12), 2942–2947. 10.2337/diacare.27.12.2942 PubMed DOI

Magerl, W. , Krumova, E. K. , Baron, R. , Tölle, T. , Treede, R. D. , & Maier, C. (2010). Reference data for quantitative sensory testing (QST): Refined stratification for age and a novel method for statistical comparison of group data. Pain, 151(3), 598–605. 10.1016/j.pain.2010.07.026 PubMed DOI

Maser, R. E. , & Lenhard, M. J. (2005). Cardiovascular autonomic neuropathy due to diabetes mellitus: Clinical manifestations, consequences, and treatment. Journal of Clinical Endocrinology and Metabolism, 90, 5896–5903. 10.1210/jc.2005-0754 PubMed DOI

Moghtaderi, A. , Bakhshipour, A. , & Rashidi, H. (2006). Validation of Michigan neuropathy screening instrument for diabetic peripheral neuropathy. Clinical Neurology and Neurosurgery, 108(5), 477–481. 10.1016/j.clineuro.2005.08.003 PubMed DOI

Orlov, S. , Bril, V. , Orszag, A. , & Perkins, B. A. (2012). Heart rate variability and sensorimotor polyneuropathy in type 1 diabetes. Diabetes Care, 35(4), 809–816. 10.2337/dc11-1652 PubMed DOI PMC

Pafili, K. , Trypsianis, G. , Papazoglou, D. , Maltezos, E. , & Papanas, N. (2020). Clinical tools for peripheral neuropathy to exclude cardiovascular autonomic neuropathy in type 2 diabetes mellitus. Diabetes Therapy, 11, 979–986. 10.1007/s13300-020-00795-0 PubMed DOI PMC

Pop‐Busui, R. , Boulton, A. J. M. , Feldman, E. L. , Bril, V. , Freeman, R. , Malik, R. A. , Sosenko, J. M. , & Ziegler, D. (2017). Diabetic neuropathy: A position statement by the American diabetes association. Diabetes Care, 40, 136–154. 10.2337/dc16-2042 PubMed DOI PMC

Rolim, L. C. , Sá, J. R. , Chacra, A. R. , & Dib, S. A. (2008). Diabetic cardiovascular autonomic neuropathy: risk factors, clinical impact and early diagnosis. Arquivos brasileiros de cardiologia, 90(4), e24–e31. 10.1590/s0066-782x2008000400014 PubMed DOI

Serhiyenko, V. A. , & Serhiyenko, A. A. (2018). Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. World Journal of Diabetes, 9(1), 1–24. 10.4239/wjd.v9.i1.1 PubMed DOI PMC

Selvarajah, D. , Cash, T. , Davies, J. , Sankar, A. , Rao, G. , Grieg, M. , Pallai, S. , Gandhi, R. , Wilkinson, I. D. , & Tesfaye, S. (2015). SUDOSCAN: A simple, rapid, and objective method with potential for screening for diabetic peripheral neuropathy. Plos One, 10(10), e0138224. 10.1371/journal.pone.0138224 PubMed DOI PMC

Singleton, J. R. , Bixby, B. , Russell, J. W. , Feldman, E. L. , Peltier, A. , Goldstein, J. , Howard, J. , & Smith, A. G. (2008). The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. Journal of the Peripheral Nervous System : JPNS, 13(3), 218–227. 10.1111/j.1529-8027.2008.00180.x PubMed DOI

Spallone, V. , Ziegler, D. , Freeman, R. , Bernardi, L. , Frontoni, S. , Pop‐Busui, R. , Stevens, M. , Kempler, P. , Hilsted, J. , Tesfaye, S. , Low, P. , Valensi, P. , & Toronto Consensus Panel on Diabetic Neuropathy . (2011). Cardiovascular autonomic neuropathy in diabetes: Clinical impact, assessment, diagnosis, and management. Diabetes/Metabolism Research and Reviews, 27, 639–653. 10.1002/dmrr.1239 PubMed DOI

Spallone, V. (2019). Update on the impact, diagnosis and management of cardiovascular autonomic neuropathy in diabetes: What is defined, what is new, and what is unmet. Diabetes & Metabolism Journal, 43(1), 3–30. 10.4093/dmj.2018.0259 PubMed DOI PMC

Tavakoli, M. , Begum, P. , McLaughlin, J. , & Malik, R. A. (2015). Corneal confocal microscopy for the diagnosis of diabetic autonomic neuropathy. Muscle & Nerve, 52(3), 363–370. 10.1002/mus.24553 PubMed DOI

Vasheghani, M. , Sarvghadi, F. , & Beyranvand, M. R. (2019). The association between cardiac autonomic neuropathy and diabetes control. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 12, 581–587. 10.2147/DMSO.S196729 PubMed DOI PMC

Vinik, A. I. , Maser, R. E. , Mitchell, B. D. , & Freeman, R. (2003). Diabetic autonomic neuropathy. Diabetes Care, 26, 1553–1579. 10.2337/diacare.26.5.1553 PubMed DOI

Yajnik, C. S. , Kantikar, V. , Pande, A. , Deslypere, J. P. , Dupin, J. , Calvet, J. H. , & Bauduceau, B. (2013). Screening of cardiovascular autonomic neuropathy in patients with diabetes using non‐invasive quick and simple assessment of sudomotor function. Diabetes & Metabolism, 39(2), 126–131. 10.1016/j.diabet.2012.09.004 PubMed DOI

Ziegler, D. , Behler, M. , Schroers‐Teuber, M. , & Roden, M. (2015). Near‐normoglycaemia and development of neuropathy: A 24‐year prospective study from diagnosis of type 1 diabetes. BMJ Open, 5(6), e006559. 10.1136/bmjopen-2014-006559 PubMed DOI PMC

Zilliox, L. , Peltier, A. C. , Wren, P. A. , Anderson, A. , Smith, A. G. , Singleton, J. R. , Feldman, E. L. , Alexander, N. B. , & Russell, J. W. (2011). Assessing autonomic dysfunction in early diabetic neuropathy: The Survey of Autonomic Symptoms. Neurology, 76(12), 1099–1105. 10.1212/WNL.0b013e3182120147 PubMed DOI PMC