ABC | Volume 111, Nº1, July 2018

Original Article Oliveira et al Nonlinear dynamics in young adults with type 1 diabetes Arq Bras Cardiol. 2018; 111(1):94-101 Individuals with DM1 may have complications such as Cardiovascular Autonomic Neuropathy (CAN), caused by damage to autonomic nerve fibers associated with the cardiovascular system, resulting in neurohumoral regulation disorders. 2 CAN may interfere with the individual’s quality of life and prognosis, showing some clinical manifestations such as resting tachycardia, exercise intolerance, stroke and sudden death of cardiac origin, among others. 3 Heart Rate Variability (HRV), a simple, reproducible and non-invasive tool that shows the oscillations between consecutive heart beats (R-R intervals) associated with the Autonomic Nervous System (ANS) influence on the sinus node, 4 is indicated for the early assessment of autonomic status in diabetic individuals. 5 Its analyses can be performed by linear methods, in the time and frequency domains, and non-linear methods, in the chaotic domain, 6 among which the symbolic analysis and entropy are highlighted. 7 The symbolic analysis has been recently studied and stands out for being able to differentiate both components of ANS 6 and quantify their impairment as a function of pathology, showing its effectiveness in assessing autonomic behavior and seeming appropriate to elucidate the neural pathophysiological mechanisms. 6,8 Shannon Entropy (SE) demonstrates the degree of complexity of signal sample distribution, 9 which allows identifying conditions that may interfere with cardiovascular regulation. 9 Few studies have used these methods to assess individuals with diabetes. 10,11 Using symbolic analysis to investigate individuals with type 2 diabetes mellitus (DM2) without CAN, Moura-Tonello et al. 10 have indicated that this population has greater sympathetic modulation and reduced parasympathetic modulation and global variability. In subjects with DM2 and CAN, entropy analyses have shown the lower complexity of these individuals when compared to individuals with DM2 without CAN. 11 HRV is a technique that allows the assessment of autonomic behavior and can be analyzed through linear and non-linear methods. 4 It is also well established that HRV indexes may be altered in several conditions – among them diabetes mellitus. Furthermore, the literature indicates that SE and symbolic analysis, a new methodology for the analysis of HRV for autonomic behavior assessment, is altered in DM2, but the use of these HRV analysis methods in patients with DM1 is unknown. Considering that DM1 more frequently affects children and young adults, and that this population is subject to several complications, including autonomic alterations, which may lead to CAN, studies such as this are necessary to identify whether the use of newmethods of autonomic activity analysis are capable of observing changes in the ANS behavior of young adults with DM1 without CAN, as well as which alterations may occur in the autonomic modulation of these individuals. Data such as these are important, because, in addition to adding elements to the literature related to the abovementioned topic, it can determine whether this type of analysis can be a relevant tool to identify and help in the understanding of DM1 influence in the autonomic modulation. The aim of the study was to compare HRV indexes obtained through symbolic analysis and SE, in young adults with DM1 and healthy subjects, associated with the analysis of the indexes obtained in the time and frequency domain, as well as to verify whether there are correlations between them for the young adults with DM1. The initial hypothesis was that the symbolic analysis and SE could identify autonomic alterations in individuals with DM1, when compared to healthy subjects, as well as the traditional HRV indexes, and that there are good correlations between such indexes. Methods To develop this cross-sectional observational study, 43 young adults diagnosed with DM1 were enrolled by convenience and allocated to the DM1 group and 45 healthy young individuals without DM1 were enrolled in the Control Group. To participate in the study, the DM1 Group volunteers should have a clinical diagnosis of DM1, confirmed by medical diagnosis and/or blood test, and no diagnosis or clinical signs of autonomic cardiac neuropathy. Neither group should have individuals with cardiorespiratory diseases and none of them were smokers and/or alcoholics. Only series of R-R intervals with more than 95% of sinus beats were included in the study, that is, series with variations in the measurement greater than 5% were disregarded. 12 To recruit the DM1 Group participants, endocrinologists and Basic Health Units were contacted and, for the Control group, students from a public university were invited to participate. To perform the sample calculation, considering the absence of studies with SE or symbolic analysis with DM1, the index corresponding to the square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD) was used, which is a classic index in HRV analysis. For the RMSSD index, considering a difference of 19.85 milliseconds, for a standard deviation of 25.30 milliseconds, 13 with an alpha risk of 5% and beta of 80%, the sample size resulted in at least 25 individuals for each group; however, for eventual device reading errors, this number was increased in both groups. All procedures used in this study followed the Helsinki Declaration and were approved by the Research Ethics Committee of Faculdade de Ciências e Tecnologia (FCT/UNESP), Presidente Prudente Campus (CAAE: 22530813.9.0000.5402, opinion 417.031). The individuals signed the Free and Informed Consent Form. Initially, the volunteers underwent an interview to collect the following information: age, gender, time of diagnosis (for diabetics) and use of medications. Body mass (Welmy R/I 200 digital scale, Brazil) and height (Sanny stadiometer, Brazil) were also measured to obtain the Body Mass Index (BMI). 14 After these assessments, volunteers were submitted to the experimental protocol, which consisted in the assessment of autonomic modulation through heart rate (HR) monitoring, using a Polar S810i cardio-frequency meter (Polar Electro, Finland), and the use of the R-R interval series obtained for the analysis of HRV. 15 95