Effect of Intensity of Acute Exercise on Heart Rate Variability in Male Patients With

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JEPonline

Effect of Intensity of Acute Exercise on Heart Rate Variability in Male Patients with Type 2 Diabetes

Yupaporn Kanpetta1,2, Nantaya Krasuaythong1,2, Chongchira Boontongkaew2,3, Terdthai Tong-un4, Naruemon Leelayuwat2,4

1Exercise and Sport Sciences Program, Graduate School, Khon Kaen University, Thailand,2Exercise and Sport Sciences Development and Research Group, Khon Kaen University, Thailand,3Biomedical Sciences Program, Graduate School, Khon Kaen University, Thailand, 4Department of Physiology, Faculty of Medicine, Khon Kaen University, Thailand

ABSTRACT

Kanpetta Y, Krasuaythong N, Boontongkaew C, Tong-un T, Leelayuwat N. Effect of Intensity of Acute Exercise on Heart Rate Variability in Male Patients with Type 2 Diabetes. JEPonline2018;21(3):94-105. We determined heart rate variability (HRV) at rest and during exercise at three intensities (low, 25%VO2peak; moderate, 65%VO2peak, and high, 85%VO2peak) in male patients with type 2 diabetes (T2D).Eight male patients with T2D randomly cycled at low, moderate, and high intensity for 10, 10, and 5 min, respectively, with 7-d apart. Electrocardiogram was recorded continuously at rest, and during exercise to analyze HRV. Compared to low-intensity exercise, the standard deviation of all NN intervals (SDNN) was significantly greater during moderate- and high-intensity exercise (P<0.05). Compared to resting, SDNN during low-intensity exercise was significantly lower and during moderate- and high-intensity exercise were higher (P<0.05). Furthermore, the low frequency domain (LF, ms2) was lower during low- and moderate-intensity exercise compared to resting (P<0.05). There were no significant differences in total power, high frequency (HF), and LF/HF among intensities and between resting and exercise. Therefore, the findings indicate that exerciseintensity influenced total HRV determined by SDNN in male patients with type 2 diabetes.

Key Words:Activity, Cardiac Autonomic Activity, Hyperglycemia

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INTRODUCTION

Type 2 diabetes mellitus (T2D) is a disease that is identified by chronic hyperglycemia mainly according to insulin resistance (12,14,25). Chronic hyperglycemia is a cause of many complications of T2D, such as cardiac autonomic dysfunction that is characterized by early and extensive neuronal degeneration of small nerve fibers of both the sympathetic and the parasympathetic tracts. This can be responsible for several disabling symptoms and even sudden cardiac death (1,27).

The impairment of cardiac autonomic activity in patients with T2D may occur in the early stage of T2D development. For this reason, it is important to detect as early as possible this impairment in T2D patients (20). One of the measurements of autonomic function is heart rate variability (HRV) (27), which is described as the beat-to-beat variation in time of consecutive heartbeats (28). It is considered to correspond to the balance between sympathetic and parasympathetic nervous system (9,23). HRV in both time (the standard deviation of all NN intervals; SDNN, the square root of the mean of the sum of the squares of differences between closest NN intervals; RMSSD and total power; TP) and frequency (the low frequency; LF: 0.04 to 0.15 Hz, the high frequency; HF: 0.15 to 0.40 Hz, and the ratio of the LF and HF; LF/HF ratio) domains have been used successfully to index sympathovagal activity (29). Previous studies reported that SDNN, LF, HF, and LF/HF were decreased in T2D patients at rest (30) and are inversely related to plasma glucose levels (26).

Among T2D prevention and treatment, exercise is considered as one of the important strategies (3). It has been known that exercise influences the alterations of HRV (8,15). However, no previous study discloses the definite effect of intensity of exercise on HRV in patients with T2D. This may provide knowledge of appropriate intensity of exercise based on the results of HRV for the prevention and treatment. Thus, the purpose of this preliminary study was investigate the HRV parameters during and after exercise at 3 intensities (low, 25%VO2peak; moderate, 65%VO2peak and high, 85%VO2peak) in male patients with T2D. We hypothesized that HRV parameters during and after exercise in T2D patients depend on intensity of exercise.

METHODS

Subjects

Eight men (30 to 60 yrs of age) from Khon Kaen, Thailand were recruited to participate in this study. They were diagnosed as T2D at least 1 yr before this participation and treated witheither metformin or glibenclamide. They did not engage in regular exercise, consume alcohol or smoke. They were informed of all the processes and risk for participation in this study. They were screened by way of a medical history, blood chemistry (complete blood cell count, glucose, lipid profile, creatinine, serum glutamic pyruvic transaminase(SGPT)) electrocardiogram (ECG), anthropometry, and health questionnaires. Exclusion criteria were consisted of subjects who were treated with insulin or other drugs, or had cardiovascular disease, hypertension, orthopedic problems or bone fracture, neuromuscular disorder, liver and kidney disease, chronic infections, and dyslipidemia.

All subjects signed an informed consent that was approved by the Human Ethical Committee of Khon Kaen University in accordance with the 1964 Declaration of Helsinki (HE561480). Thai Clinical Trials Registry (TCTR) identification number is TCTR20180124004. TCTR is obliged to disclose details of the 20 mandatory items of the WHO International Clinical Trials Registry Platform (WHO-ICTRP) dataset.

Study Design and Procedures

This study was a randomized crossover design. All subjects randomly participated in three visits of exercise atlow-intensity (25%VO2peak), moderate-intensity (65%VO2peak), and high-intensity (85%VO2peak) with at least 7 d apart.All subjects were asked to refrain from alcoholic beverage and vigorous exercise before the test and on the evening before the visit. They started the experiment with performing a peak oxygen consumption test (VO2peak) to set workloads at the predetermined intensities.

The peak oxygen consumption test (VO2peak) is an incremental test on the electromagnetically braked cycle ergometer (Corival, Lode, Groningen, The Netherlands) until exhaustion. All subjects refrained from alcohol and caffeine ingestion as well as performing heavy exercise 2 hrs before the test. They began the test with warming up at free workload (0 watt) for 2 min and then at a workload of 30 watts for 3 min. The workload was increased 20 to 30 watts every 3 min depending on the subjects’ physical fitness status. All subjects performed the test until their heart rate (HR)reached 85% of the predicted HRmax(220-age) or until they reached the termination criteria, including the cycling speed lower than 60 rev·min-1,a respiratory exchange ratio (RER) above 1.15, an oxygen consumption that failed to increase with increased work rate, a rating of perceived exertion (RPE) of 19 to 20, and a rating of perceived dyspnea (RPD) of 9 to 10 (2). The termination criteria were conducted according to the British Association of Sport and Exercise Science (BASES).

During VO2peak and exercise tests, expired-air samples were collected by a gas analysis system (AD instrument, ML206, Australia) that was calibrated before every trial.At least 7 d later, they randomly participated in three visits of exercise at different intensities with a 7 d interval between each to eliminate any carry over effect. They performed the same procedure at the same time of the day. They reported tothe laboratory at 7.30 a.m. after an 8-hr overnight fast. At 8:00 a.m. they rested for 30 min. After resting period, they randomly performed an exercise test on the electromagnetically braked cycle ergometer at 25%VO2peak for 10 min or 65%VO2peak for 10 min or 85% VO2peak for 5 min. The average room temperature was 25.4±.7°C and the average humidity was 52.6±4%.ECGand blood pressure (BP) were recorded throughout the experiment to assess HR and BP.

Measurements of Main Outcomes

The subjects’ HRV was analyzed during thelast 5 min of baseline, exercise, and recovery. HRV was determined by ECG recording, using LabChart® version 6 (Ad Instruments, Sydney, Australia). The ECG signals was sampled at a frequency of 1000 Hz and stored in a computer. The time domain variables included the SDNN, which was used to estimate the overall HRV, and RMSSD that reflects vagal activity. For frequency domain (ms2), the LF component reflects both sympathetic and vagal activity. The HF component is the integral from 0.15 to 0.40 Hz. It evaluates predominantly vagal activity. LF/HF ratio is calculated to indicate sympathovagal balance (4,28).Blood pressure was recorded by Life Scope I BSM-2301/2303 (NIHON KOHDEN, Kuala Lumpur,Malaysia)

Statistical Analyses

Baseline characteristics data were expressed as mean ± SD while other parameters were expressed as mean ± SE. STATA version 12 was used to test the statistics. Repeated measure ANOVA was used to compare all parameters between groups, Turkey’s post hoc test was applied in case of significance (P<0.05). Normal distribution of the data was confirmed by creatinga histogram.

RESULTS

Anthropometric and Blood Chemistry Parameter

Baseline anthropometric and blood chemistrycharacteristics of all subjects were shown in Table 1 and Table 2, respectively. All subjects had hyperglycemia but normal liver and renal function. Some subjects had dyslipidemia.

Table 1.Baseline Characteristics of Male Patients with T2D.

Variables / Mean ± SD
Age (yr) / 52 ± 8.2
Body Mass (kg) / 68.6 ± 7.0
Height (m) / 1.63 ± 0.1
BMI (kg/m2) / 24.9 ± 1.8
Waist Circumference (cm) / 88.6 ± 7.1
Hip Circumference (cm) / 97.4 ± 4.5
W/H ratio / 0.9 ± 0.0
SBP (mmHg) / 129 ± 15.7
DBP (mmHg) / 79 ± 9.4

Table 2. Baseline Blood Chemistry of Male Patients with T2D (N=8).

Variables / Mean ± SD
Glucose (mmoL/moL) / 7.22 ± 2.0
Hemoglobin A1c(mmoL/moL) / 59.4 ± 8.7
Hemoglobin A1c (%) / 7.6 ± 0.8
Creatinine (mg/dL) / 0.9 ± 0.2
Serum Glutamic-Pyruvic Transaminase(U/L) / 19.1 ± 7.3
Total Cholesterol (mmoL/moL) / 4.79 ± 0.9
Triglyceride (mmoL/moL) / 1.69 ± 0.8
High Density Lipoprotein-Cholesterol (mmoL/moL) / 1.09 ± 0.3
Low Density Lipoprotein-Cholesterol (mmoL/moL) / 3.32 ± 0.3

Physiological Parameters

The HR and BPmeasurements are shown in Table 3. All subjects had normal resting HR and BP. The subjects’ HR increased with intensity of exercise (P<0.05). Systolic blood pressure (SBP) at high-intensity was higher than that at low-intensity (P<0.05), andSBP at moderate-intensity and high-intensity exercise were significantly increased when compared to baseline and recovery (P<0.05) values. There were no changes in the subjects’ diastolic blood pressure (DBP) from baseline throughout the different exercise intensities.

Table 3. Heart Rate, Blood Pressure, and Percentage of Peak Oxygen Consumption at Baseline, during Exercise, and Recovery after Exercise at Various Intensities in MalePatients with T2D.

Variables / Intensity / Baseline / Exercise / Recovery
Heart Rate (/min) / Low / 74 ± 2.2 / 85 ± 4.8 / 74 ± 1.3
Moderate / 74 ± 2.5* / 110 ± 3.7@ / 74 ± 3.5*
High / 72 ± 3.1* / 130 ± 4.6@,$ / 78 ± 3.4*
Systolic Blood Pressure (mmHg) / Low / 129 ± 5.5 / 130 ± 4.4 / 126 ± 6.5
Moderate / 123 ± 6.3* / 134 ± 8.2 / 125 ± 6.4*
High / 126 ± 4.9* / 145 ± 8.9@ / 129 ± 3.6*
Diastolic Blood Pressure (mmHg) / Low / 79 ± 3.3 / 74 ± 3.1 / 77 ± 3.1
Moderate / 75 ± 2.1 / 77 ± 4.2 / 77 ± 3.1
High / 78 ± 2.8 / 83 ± 4.7 / 79 ± 3.6
%VO2Peak / Low / 29 ± 1.0
Moderate / 62 ± 1.1@
High / 82 ± 1.1@,$

Data are expressed as mean ± SE,N=8. Baseline =Before Exercise, During =During Exercise, Recovery = 30 minAfter Exercise, VO2peak =Peak Oxygen Consumption. *Significantly different from exercise (P<0.05), @Significantly different from low-intensity exercise (P<0.05), $Significantly different from moderate-intensity exercise (P<0.05)

HRV Parameters

Figure 1 summarizes the HRV parameters. The subjects had significantly lower and higher SDNN during exercise at low-intensity and high-intensity, respectively, than baseline and recovery (P<0.05). However, there was no change on any time points in SDNN at moderate- intensity. During exercise, SDNN at low-intensity was significantly lower than at moderate-intensity and high-intensity (P<0.05). In addition, LF (ms2) was significantly lower during exercise at low-intensity and moderate-intensity than at baseline and recovery (P<0.05). There were no significant differences in TP, HF, and LF/HF among intensities and between resting and exercise.

Interaction

There was a significant interaction between time and intensity in SDNN (P=0.001). In addition, there were the effects of time on SDNN (P=0.002) and LF (ms2) (P=0.001).

Figure 1. HRV Parameters at Baseline, During Exercise, and Recovery After Exercise at Various Intensities in Male Patients with T2D. Data are expressed as mean ± SE,N = 8. Baseline =Before Exercise, During =During Exercise, Recovery = 30 minAfter Exercise, SDNN = The Standard Deviation of all NN Intervals, RMSSD = The Square Root of the Mean of the Sum of the Squares of Differences between Closest NN Intervals, TP = Total Power, LF =Low Frequency Domain, HF =High Frequency Domain, LF/HF= Ratio of the Low Frequency and High Frequency.*Significantly different from exercise (P<0.05), @Significantly different from low-intensity exercise (P<0.05)

DISCUSSION

The novel finding of this study is that male patients with T2D had higher total HRV during moderate-intensity and during high-intensity exercise than during low-intensity exercise. In addition, total HRV was decreased during the low-intensity exercise but increased during the moderate-intensity and high-intensity exercises compared with resting condition. All changesduring the different exercise intensities disappeared during recovery.

The present study appears to be the first to investigate the changes of HRV in response to a single bout of exercise at low-intensity (25%VO2peak), moderate-intensity (65%VO2peak) and high-intensity (85%VO2peak) exercise in maleswith T2D. The duration of exercise at the three intensities in this study was chosenaccording to an earlier pilot study in which we found that 10 min for low-intensity and moderate-intensity and 5 min for high-intensity exercise are practicallengths of time for these patients to perform. Moreover, it was long enough to investigate the HRV parameters(25).

The method used to assess HRV in the present study wasa short-term 5-min ECG recording that was shown to be valid (25). This method was used because we wanted to measure HRV during exercise thatwould last for 5 to 10 min. Thus, the use of the 24-hr ECG recording that is known to be a better HRV measurement was not reasonable in the present study.

HRV has considerable potential to assess fluctuations in cardiac autonomic nervous activity in patients with various cardiovascular and non-cardiovascular disorders that include T2D (19,25,28). Kondo et al. (17) also reported that T2D patients had lower LF/HF ratio than non-diabetes control subjects during a 24-hr ECG monitoring. The impaired sympathovagal activity in the T2D patients was triggered by dysglycemia, which is supported by the work of Neves and colleagues (19). They reported negative correlation between TP and AUC-glucose, cholesterol and triglyceride levels in T2D patients. The low total HRV in patients with T2D in the study by Singh et al. (26)was indicated by time (SDNN) and frequency (TP, LF, and LF/HF) domains (26).

Singh et al. (26) concluded that more research is necessary to determine if low HRV does contribute to increased cardiovascular morbidity and mortality in hyperglycemic subjects. In fact, according to Singhand colleagues (26), although their subjects had a high risk of myocardial infarction,they had no symptom of cardiovascular diseases even though autonomic neuropathy is characterized by early and widespread neuronal degeneration of both sympathetic and parasympathetic tracts. However, it is important to point out that the population studies such as Tiftikcioglu et al. (30) are the population of the present study. As such, then, a study that publishes norms of HRV parameters of age- and sex-matched, non-diabetic healthy Thai population needs to be done to confirm the interpretation.

Recently, a literature review by Shaffer andGinsberg (25) suggested that higher HRV is not always better since some pathology can increase HRV. For example, cardiac conduction abnormalities such as atrial fibrillation can increase HRV, which is linked to the increased risk of mortality. Thus, ECG morphology can reveal whether elevated HRV values are better or worse (6). In the present study, all the subjects had normal ECG both at rest and during exercise. Therefore, the higher total HRV determined by SDNN during moderate-intensity and high-intensity exercise compared with low-intensity exercise could imply improvement in cardiac autonomic activity during the higher intensities.

Taken together with the improved total HRV, moderate-intensity and high-intensity exercise are recommended for these patients. However, we suggest that moderate-intensity exercise seems to be more appropriate because of its less harmful effect.Exercise at high-intensity may cause an excessive increase in BP, exercise-induced arrhythmias or tissue damage. In addition, the present study found decreased LF during exercise at low-intensity and moderate-intensity. This finding was consistent with the study by Kasahara et al. (15).The authors found that LF was significantly reduced during low-intensity exercise at 20%HRmax in T2D patients with an acute myocardial infarction. Based on the knowledge of increased sympathetic activity during exercise, it appears that LF in their study did not determine sympathetic activity (15).

In the present study, HR was increased with intensity of exercise in T2D patients. This result confirms the increased exercise intensity because of sympathetic excitation during exercise(18). These findings are similar to the results in non-diabetes healthy subjects who cycled on ergometer for 8 min at low-intensity (40 to 45%HRreserve), moderate- intensity (75 to 80%HRreserve), and high-intensity (90 to 95%HRreserve)(18).These effects are reversed duringa certain duration of recovery after exercise (7,15).

During recovery, the present study did not find the effect of intensity of exercise on any HRV parameters in male patients with T2D. This phenomenon is consistent with a previous study by Figueroa et al. (8) who also evaluated T2D patients, but their subjects were obese lean women. They found that 30 min after moderate-exercise (65%VO2peak), LF (Ln mmHg2), HF (Ln ms2) and LF/HF ratio returned to baseline in all subjects. Their findings are in contrast to a previous study by Raczak et al. (22). They evaluated sedentary healthy male subjects who performed a treadmill exercise for 30 min at low-intensity (65%HRmax) following by a 60-minrecovery period. Raczak et al. (22) reported that the single bout of low-intensity exercise improved SDNN at recovery after the exercise without any changes in other HRV parameters.

The effects of health status and recovery duration may be responsible for the discrepancy in the findings. However, there are several studies (16,24,31,32)on healthy subjects that foundwomen had greater increases of parasympathetic activity at rest and during exercise than did the men. This may be due to the buffering by the autonomic advantages with long-term exposure to estrogen (10,14,31). Estrogen is thought to provide numerous cardiovascular benefits through both genomic and non-genomic effects on the synthesis and release of nitric oxide (NO) that is associated with the increase in vagal activity of women (21). There was no study that explored the effects of gender and intensity of exercise in patients with T2D. Thus, further study exploring the gender effect on HRV during and after exercise of various intensities should be performed.