Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet

Overview

Journal Diabetes Metab J

Specialty Endocrinology

Date 2019 Feb 23

PMID 30793549

Citations 99

Authors

Vincenza Spallone

Affiliations

Soon will be listed here.

Abstract

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.

Citing Articles

Electrodiagnostic assessment of autonomic nervous system in diabetic autonomic neuropathy: Case series in 72 diabetes patients.

Dube S, Hulke S, Wakode S, Khadanga S J Family Med Prim Care. 2025; 14(1):452-457.

PMID: 39989573 PMC: 11844996. DOI: 10.4103/jfmpc.jfmpc_1128_24.

Comparative study of autonomic function in diabetics and yoga practitioners using Ewing's battery.

Amadawala T, Rukadikar C, Deshpande D J Family Med Prim Care. 2025; 14(1):121-125.

PMID: 39989517 PMC: 11844941. DOI: 10.4103/jfmpc.jfmpc_749_24.

Correlation between Sirtuin 1 downregulation and reduced vitamin D receptor expression in patients with diabetic neuropathy.

Latini A, De Benedittis G, Morgante C, Gasperini B, DIppolito I, Lauro D Acta Diabetol. 2025; .

PMID: 39976627 DOI: 10.1007/s00592-025-02463-w.

Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review.

Gogan A, Potre O, Avram V, Andor M, Caruntu F, Timar B J Clin Med. 2025; 14(3).

PMID: 39941342 PMC: 11818907. DOI: 10.3390/jcm14030671.

D1S-Neuro Program: Frequency and Risk Factors for the Development of Diabetic Neuropathy in Pediatric Patients with Type 1 Diabetes Mellitus, a Single Center Study.

Piccoli M, Gutierrez De Rubalcava Doblas J, Furlan P, Cocchio S, Zamberlan A, Panzeri G Biomedicines. 2025; 13(1.

PMID: 39857602 PMC: 11762328. DOI: 10.3390/biomedicines13010019.

References

Hansen T, Li Y, Boggia J, Thijs L, Richart T, Staessen J . Predictive role of the nighttime blood pressure. Hypertension. 2010; 57(1):3-10. DOI: 10.1161/HYPERTENSIONAHA.109.133900. View

Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R . Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011; 27(7):639-53. DOI: 10.1002/dmrr.1239. View

Sauder K, McCrea C, Ulbrecht J, Kris-Etherton P, West S . Pistachio nut consumption modifies systemic hemodynamics, increases heart rate variability, and reduces ambulatory blood pressure in well-controlled type 2 diabetes: a randomized trial. J Am Heart Assoc. 2014; 3(4). PMC: 4310367. DOI: 10.1161/JAHA.114.000873. View

Martin C, Albers J, Pop-Busui R . Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2013; 37(1):31-8. PMC: 3868000. DOI: 10.2337/dc13-2114. View

Vinik A, Camacho P, Davidson J, Handelsman Y, Lando H, Leddy A . AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE DYSFUNCTION. Endocr Pract. 2018; 23(12):1472-1478. DOI: 10.4158/EP-2017-0053. View

Zoppini G, Cacciatori V, Raimondo D, Gemma M, Trombetta M, Dauriz M . Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS). Diabetes Care. 2015; 38(8):1487-93. DOI: 10.2337/dc15-0081. View

Ziegler D, Voss A, Rathmann W, Strom A, Perz S, Roden M . Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia. 2015; 58(5):1118-28. DOI: 10.1007/s00125-015-3534-7. View

Lachin J, Bebu I, Bergenstal R, Pop-Busui R, Service F, Zinman B . Association of Glycemic Variability in Type 1 Diabetes With Progression of Microvascular Outcomes in the Diabetes Control and Complications Trial. Diabetes Care. 2017; 40(6):777-783. PMC: 5439414. DOI: 10.2337/dc16-2426. View

Pennathur S, Jaiswal M, Vivekanandan-Giri A, White E, Ang L, Raffel D . Structured lifestyle intervention in patients with the metabolic syndrome mitigates oxidative stress but fails to improve measures of cardiovascular autonomic neuropathy. J Diabetes Complications. 2017; 31(9):1437-1443. PMC: 5580245. DOI: 10.1016/j.jdiacomp.2017.03.008. View

10.

Schroeder E, Chambless L, Liao D, Prineas R, Evans G, Rosamond W . Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care. 2005; 28(3):668-74. DOI: 10.2337/diacare.28.3.668. View

11.

Shaw B, Garland E, Black B, Paranjape S, Shibao C, Okamoto L . Optimal diagnostic thresholds for diagnosis of orthostatic hypotension with a 'sit-to-stand test'. J Hypertens. 2017; 35(5):1019-1025. PMC: 5542884. DOI: 10.1097/HJH.0000000000001265. View

12.

Loimaala A, Huikuri H, Koobi T, Rinne M, Nenonen A, Vuori I . Exercise training improves baroreflex sensitivity in type 2 diabetes. Diabetes. 2003; 52(7):1837-42. DOI: 10.2337/diabetes.52.7.1837. View

13.

May O, Arildsen H . Assessing cardiovascular autonomic neuropathy in diabetes mellitus: how many tests to use?. J Diabetes Complications. 2000; 14(1):7-12. DOI: 10.1016/s1056-8727(00)00062-3. View

14.

Annuzzi G, Rivellese A, Vaccaro O, Ferrante M, Riccardi G, Mancini M . The relationship between blood glucose concentration and beat-to-beat variation in asymptomatic subjects. Acta Diabetol Lat. 1983; 20(1):57-62. DOI: 10.1007/BF02629130. View

15.

Tiftikcioglu B, Bilgin S, Duksal T, Kose S, Zorlu Y . Autonomic Neuropathy and Endothelial Dysfunction in Patients With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus. Medicine (Baltimore). 2016; 95(14):e3340. PMC: 4998830. DOI: 10.1097/MD.0000000000003340. View

16.

Kim Y, Lee J, Kim Y, Kim D, Oh H, Yang C . Cardiac autonomic neuropathy as a predictor of deterioration of the renal function in normoalbuminuric, normotensive patients with type 2 diabetes mellitus. J Korean Med Sci. 2009; 24 Suppl:S69-74. PMC: 2633204. DOI: 10.3346/jkms.2009.24.S1.S69. View

17.

Burger A, DElia J, Weinrauch L, Lerman I, Gaur A . Marked abnormalities in heart rate variability are associated with progressive deterioration of renal function in type I diabetic patients with overt nephropathy. Int J Cardiol. 2002; 86(2-3):281-7. DOI: 10.1016/s0167-5273(02)00346-7. View

18.

Kim S, Lee K, Jin H, Baek H, Park T . Relationship between the Korean Version Survey of the Autonomic Symptoms Score and Cardiac Autonomic Neuropathy Parameters in Patients with Diabetic Peripheral Neuropathy. Diabetes Metab J. 2014; 38(5):349-55. PMC: 4209349. DOI: 10.4093/dmj.2014.38.5.349. View

19.

Dimova R, Tankova T, Guergueltcheva V, Tournev I, Chakarova N, Grozeva G . Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance. J Diabetes Complications. 2016; 31(3):537-543. DOI: 10.1016/j.jdiacomp.2016.11.002. View

20.

Yun J, Ahn Y, Song K, Yoo K, Kim H, Park Y . The association between abnormal heart rate variability and new onset of chronic kidney disease in patients with type 2 diabetes: a ten-year follow-up study. Diabetes Res Clin Pract. 2015; 108(1):31-7. DOI: 10.1016/j.diabres.2015.01.031. View