Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Research Article

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals

Author(s): Yeelen Ballesteros Atala*, Mozânia Reis De Matos*, Denise Engelbrecht Zantut-Wittmann, Alejandro Rosell Castillo, Daniele P Santos-Bezerra, Maria Lucia Correa-Giannella* and Maria Cândida Ribeiro Parisi*

Volume 18, Issue 4, 2022

Published on: 06 January, 2022

Article ID: e270821195908 Pages: 7

DOI: 10.2174/1573399817666210827130339

Price: $65

Abstract

Background: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases.

Objective: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies.

Methods: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting.

Results: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak.

Conclusion: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Keywords: Cardiac autonomic neuropathy, diabetes mellitus, diabetic neuropathy, autonomic dysfunction, CARTs, heart rate variability.

[1]
Benichou T, Pereira B, Mermillod M, et al. Heart rate variability in type 2 diabetes mellitus: A systematic review and meta-analysis. PLoS One 2018; 13(4): e0195166.
[http://dx.doi.org/10.1371/journal.pone.0195166] [PMID: 29608603]
[2]
Singh JP, Larson MG, O’Donnell CJ, et al. Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study). Am J Cardiol 2000; 86(3): 309-12.
[http://dx.doi.org/10.1016/S0002-9149(00)00920-6] [PMID: 10922439]
[3]
Kim MY, Kim G, Park JY, et al. Relationship Between Core Continuous Glucose Monitoring Metrics, including Time in Range, and Cardiovascular Autonomic Neuropathy in Outpatients with Type 2 Diabetes. Diabetes Technol Ther 2021; 23(6): 434-2.
[http://dx.doi.org/10.1089/dia.2020.0599] [PMID: 33523771]
[4]
O’Brien IA, McFadden JP, Corrall RJM. The influence of autonomic neuropathy on mortality in insulin-dependent diabetes. Q J Med 1991; 79(290): 495-502.
[PMID: 1946930]
[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(7): 639-53.
[http://dx.doi.org/10.1002/dmrr.1239] [PMID: 21695768]
[6]
Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes 2014; 5(1): 17-39.
[http://dx.doi.org/10.4239/wjd.v5.i1.17] [PMID: 24567799]
[7]
Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Investig 2013; 4(1): 4-18.
[http://dx.doi.org/10.1111/jdi.12042] [PMID: 23550085]
[8]
Low PA, Benrud-Larson LM, Sletten DM, et al. Autonomic symptoms and diabetic neuropathy: a population-based study. Diabetes Care 2004; 27(12): 2942-7.
[http://dx.doi.org/10.2337/diacare.27.12.2942] [PMID: 15562211]
[9]
Maser RE, Lenhard MJ. Cardiovascular autonomic neuropathy due to diabetes mellitus: clinical manifestations, consequences, and treatment. J Clin Endocrinol Metab 2005; 90(10): 5896-903.
[http://dx.doi.org/10.1210/jc.2005-0754] [PMID: 16014401]
[10]
Yun JS, Kim JH, Song KH, et al. Cardiovascular autonomic dysfunction predicts severe hypoglycemia in patients with type 2 diabetes: a 10-year follow-up study. Diabetes Care 2014; 37(1): 235-41.
[http://dx.doi.org/10.2337/dc13-1164] [PMID: 23959567]
[11]
Low PA. Prevalence of orthostatic hypotension. Clin Auton Res 2008; 18(Suppl. 1): 8-13.
[http://dx.doi.org/10.1007/s10286-007-1001-3] [PMID: 18368301]
[12]
Low PA, Walsh JC, Huang CY, McLeod JG. The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study. Brain 1975; 98(3): 341-56.
[http://dx.doi.org/10.1093/brain/98.3.341] [PMID: 810214]
[13]
Weimer LH. Autonomic testing: common techniques and clinical applications. Neurologist 2010; 16(4): 215-22.
[http://dx.doi.org/10.1097/NRL.0b013e3181cf86ab] [PMID: 20592565]
[14]
Colombo J, Arora R, DePace NL, Vinik AI. Autonomic (parasympathetic and sympathetic) assessment. Clinical autonomic dysfunction springer, cham t. Switzerland: Springer international publishing 2015; pp. 77-84.
[15]
Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985; 8(5): 491-8.
[http://dx.doi.org/10.2337/diacare.8.5.491] [PMID: 4053936]
[16]
Agashe S, Petak S. Cardiac autonomic neuropathy in diabetes mellitus. Methodist DeBakey Cardiovasc J 2018; 14(4): 251-6.
[PMID: 30788010]
[17]
Rajendra Acharya U, Paul Joseph K, Kannathal N, Lim CM, Suri JS. Heart rate variability: a review. Med Biol Eng Comput 2006; 44(12): 1031-51.
[http://dx.doi.org/10.1007/s11517-006-0119-0] [PMID: 17111118]
[18]
Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007; 115(3): 387-97.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.634949] [PMID: 17242296]
[19]
Vinik AI, Erbas T. Diabetic autonomic neuropathy. Handb Clin Neurol 2013; 117: 279-94.
[http://dx.doi.org/10.1016/B978-0-444-53491-0.00022-5] [PMID: 24095132]
[20]
Ziegler D. Cardiovascular autonomic neuropathy: clinical manifestations and measurement. Diabetes Rev (Alex) 1999; 7: 300-15.
[21]
Lefrandt JD, Smit AJ, Zeebregts CJ, Gans RO, Hoogenberg KH. Autonomic dysfunction in diabetes: A consequence of cardiovascular damage. Curr Diabetes Rev 2010; 6(6): 348-58.
[http://dx.doi.org/10.2174/157339910793499128] [PMID: 20879972]
[22]
Robbe HW, Mulder LJ, Rüddel H, Langewitz WA, Veldman JB, Mulder G. Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension 1987; 10(5): 538-43.
[http://dx.doi.org/10.1161/01.HYP.10.5.538] [PMID: 3666866]
[23]
Pop-Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care 2017; 40(1): 136-54.
[http://dx.doi.org/10.2337/dc16-2042] [PMID: 27999003]
[24]
Spallone V. Update on the impact, diagnosis and management of cardiovascular autonomic neuropathy in diabetes: What is defined, what is new, and what is unmet. Diabetes Metab J 2019; 43(1): 3-30.
[http://dx.doi.org/10.4093/dmj.2018.0259] [PMID: 30793549]
[25]
Bernardi L, Spallone V, Stevens M, et al. Methods of investigation for cardiac autonomic dysfunction in human research studies. Diabetes Metab Res Rev 2011; 27(7): 654-64.
[http://dx.doi.org/10.1002/dmrr.1224] [PMID: 21695761]
[26]
National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand (Chronic Heart Failure Guidelines Expert Writing Panel. Guidelines for the prevention, detection, and management of chronic heart failure in Australia 2011; 27(10): 1123-208.
[27]
Young MJ, Boulton AJM, MacLeod AF, Williams DR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the united kingdom hospital clinic population. Diabetologia 1993; 36(2): 150-4.
[http://dx.doi.org/10.1007/BF00400697] [PMID: 8458529]
[28]
Agelink MW, Malessa R, Baumann B, et al. Standardized tests of heart rate variability: Normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate. Clin Auton Res 2001; 11(2): 99-108.
[http://dx.doi.org/10.1007/BF02322053] [PMID: 11570610]
[29]
Fleiss JL. Statistical methods for rates and proportions. 2nd ed. New York: John Wiley & Sons Inc 1981.
[30]
Bissinger A. Cardiac autonomic neuropathy: Why should cardiologists care about that?.J Diabetes Res 2017; 2017: 5374176.
[31]
Xue Y, Lv Y, Tang Z, Dong J. Analysis of a screening system for diabetic cardiovascular autonomic neuropathy in China. Med Sci Monit 2017; 23: 5354-62.
[http://dx.doi.org/10.12659/MSM.905240] [PMID: 29125834]
[32]
Jin J, Wang W, Zhu L, et al. Cardiovascular autonomic neuropathy is an independent risk factor for left ventricular diastolic dysfunction in patients with type 2 diabetes. Biomed Res Int 2017; 2017: 3270617.
[33]
Rathmann W, Ziegler D, Jahnke M, Haastert B, Gries FA. Mortality in diabetic patients with cardiovascular autonomic neuropathy. Diabet Med 1993; 10(9): 820-4.
[http://dx.doi.org/10.1111/j.1464-5491.1993.tb00173.x] [PMID: 8281726]
[34]
Gerritsen J, Dekker JM, TenVoorde BJ, et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study. Diabetes Care 2001; 24(10): 1793-8.
[http://dx.doi.org/10.2337/diacare.24.10.1793] [PMID: 11574444]
[35]
Pop-Busui R, Evans GW, Gerstein HC, et al. Effects of cardiac autonomic dysfunction on mortality risk in the action to control cardiovascular risk in diabetes (ACCORD) trial. Diabetes Care 2010; 33(7): 1578-84.
[http://dx.doi.org/10.2337/dc10-0125] [PMID: 20215456]
[36]
Cipriani M, Paggetti C, Fattorini L, Macerata A, Gensini GF. Power spectrum analysis of heart rate variations in the early detection of diabetic autonomic neuropath. Clin Auton Res 1994; 4: 245-8.
[http://dx.doi.org/10.1007/BF01827429]
[37]
Lombardi F, Huikuri H, Schmidt G, Malik M. Short-term heart rate variability: Easy to measure, difficult to interpret. Heart Rhythm 2018; 15(10): 1559-60.
[http://dx.doi.org/10.1016/j.hrthm.2018.05.023] [PMID: 29803853]
[38]
Howorka K, Pumprla J, Schabmann A. Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy. J Auton Nerv Syst 1998; 69(2-3): 164-72.
[http://dx.doi.org/10.1016/S0165-1838(98)00015-0] [PMID: 9696273]
[39]
Tang ZH, Wang L, Zeng F, et al. Bayesian estimation of cardiovascular autonomic neuropathy diagnostic test based on short-term heart rate variability without a gold standard. BMJ Open 2014; 4(9): e005096.
[http://dx.doi.org/10.1136/bmjopen-2014-005096] [PMID: 25287103]
[40]
Lai YR, Huang CC, Cheng BC, et al. Feasibility of combining heart rate variability and electrochemical skin conductance as screening and severity evaluation of cardiovascular autonomic neuropathy in type 2 diabetes. J diabetes investig 2021; 12(9): 1671-9.
[http://dx.doi.org/10.1111/jdi.13518] [PMID: 33522129]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy