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HRV and Type 2 Diabetes 23 Journal of Exercise Physiologyonline (JEPonline) Volume 12 Number 4 August 2009 Managing Editor Exercise and Health Tommy Boone, PhD, MPH Editor-in-Chief Effect of High Intensity Interval Training on Heart Rate Variability in Jon K. Linderman, PhD Review Board Individuals with Type 2 Diabetes Todd Astorino, PhD Julien Baker, PhD KOULLA M. PARPA, MARCOS A. MICHAELIDES, BARRY S. BROWN Tommy Boone, PhD Larry Birnbaum, PhD Human Performance Laboratory/Department of Health Science, Kinesiology, Eric Goulet, PhD Recreation and Dance, University of Arkansas, Fayetteville, USA Robert Gotshall, PhD M. Knight-Maloney, PhD Len Kravitz, PhD ABSTRACT James Laskin, PhD Derek Marks, PhD Parpa KM, Michaelides MA, Brown BS. Effect of High Intensity Interval Cristine Mermier, PhD Training on Heart Rate Variability in Individuals with Type 2 Diabetes. Chantal Vella, PhD JEPonline 2009;12 (4): 23-29. The purpose of the study was to examine Ben Zhou, PhD the effect of high intensity interval training (HIIT) on cardiovascular Official autonomic function as determined by HRV, in individuals with diabetes. Research Journal of Fourteen sedentary individuals (9 females, 5 males, age: 57±6.7 years, the American Society of weight: 94.3 ± 23.8 kg, height: 170.5 ±8.5 cm) met all inclusion criteria Exercise Physiologists for the study. Resting electrocardiogram (ECG) was recorded at (ASEP) baseline and 12-weeks after training. HRV was assessed manually from ISSN 1097-975 calculation of the mean R-R interval and its standard deviation measured on a 5-min ECG. Participants followed a 12-week HIIT on a treadmill consisting of four ~30-min sessions per week. A HIIT session involved a 3- minute warm-up period, six short (two minutes) maximum- intensity (80-90% heart rate max) efforts separated by six moderate intensity (50-60% heart rate max) recovery intervals (two minutes) and a 3-minute cool down period. Results demonstrated a statistically significant difference in HRV pre (HRV: 52.80 ± 8.5 ms) compared to post training (HRV: 62.60 ± 11.00 ms), t(13) = -7.46, p = 0.0001. In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate (RHR), fasting glucose values (FG) and body weight were significantly lower following 12 weeks of training. The beneficial effect on autonomic regulation as a result of exercise training may have clinical importance in preventing adverse cardiovascular events in individuals with diabetes. Key Words: Autonomic Function, EKG, Disease, Activity. HRV and Type 2 Diabetes 24 INTRODUCTION Type 2 diabetes is a serious costly disease with several complications and premature mortality (1). More than 65 percent of deaths in individuals with diabetes are attributed to heart and vascular disease (1). In studying the effects of exercise on type 2 diabetes, many studies have reported positive effects of aerobic exercise training (2) as well as strength training (3) on muscle quality, whole body insulin sensitivity, body composition (4) and blood pressure (5). In addition, it has been demonstrated that 30 minutes of moderate intensity continuous cycling or treadmill exercise on most days of the week can significantly increase heart rate variability (HRV) in individuals with type 2 diabetes (6). Consistent and extensive data have indicated that reduced cardiac autonomic control as determined by the amount of short and long term variability in heart rate is an independent risk factor for coronary heart disease and all cause mortality (7). Research have demonstrated that the relative risk of mortality is 5.3 times higher when HRV is less than 50 ms compared to when HRV is greater than 100 ms in individuals with acute myocardial infarction (8). Also, it has been reported that HRV is lower in individuals with hypertension (9) dyslipidemia and type 2 diabetes (10). Lower HRV in individuals with diabetes has been significantly related to the development of coronary heart disease independent of the duration and severity of the glucose metabolism impairment (11). The Atherosclerosis Risk in Communities (ARIC) study, which investigated the consequence of diabetes and pre-diabetic metabolic impairments on a 9-year change on HRV, demonstrated that cardiac autonomic impairment was present in early stages of diabetes. In addition, autonomic cardiac function was progressively worsened in individuals with type 2 diabetes. Despite the documented evidence (6) of the benefits of continuous cycling or treadmill training on autonomic nervous system balance, a recent study demonstrated that only 38% of adults with diabetes were engaged in moderate to vigorous activities three or more times a week (12). Among the most common barriers to physical activity were the perceived difficulty when exercising and feelings of tiredness (12). It would appear there is a need for alternate forms of exercise training that produce similar improvements to continuous exercise and could be beneficial in improving cardiovascular autonomic function in individuals with diabetes. A possible alternative is the use of interval training. Previous studies have indicated that HIIT is superior to moderate intensity continuous training in improving endothelial function, aerobic capacity, and quality of life in patients with post infarction heart failure (13). Moreover, it has been demonstrated that HIIT is superior to moderate intensity training in reversing risk factors of the metabolic syndrome (14). Even though previous studies have demonstrated that continuous aerobic exercise training can result in significant improvement in HRV in patients after coronary angioplasty (15), individuals with coronary artery disease (16) and those on hemodialysis (17), no studies have been published that assess the effects of HIIT on HRV in individuals with type 2 diabetes. Therefore, the significance of this study is to add to the limited body of scientific knowledge regarding the effect of HIIT on cardiovascular autonomic function in individuals with diabetes. It is hypothesized that mean HRV will be significantly greater post- compared to pre training. In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate (RHR), fasting glucose (FG) and body weight are expected to be significantly lower post- compared to pre training. METHODS Subjects Approval of the study protocol by the University of Arkansas Institutional Review Board for Human Subjects was secured prior to the beginning of the study. Participants for the study were 19 HRV and Type 2 Diabetes 25 individuals with type 2 diabetes. Five participants dropped out early in the study due to personal reasons. Therefore, the results presented are from 14 sedentary individuals (9 females, 5 males, age: 57±6.7 years, weight: 94.3 ± 23.8 kg, height: 170.5 ±8.5 cm) who completed the 12 week intervention. Inclusion criteria involved: A written approval from their physician to participate in the exercise portion of the study, no more than 2 risk factors (in addition to diabetes) on the Physical Activity Readiness Questionnaire, at least moderate glycemic control, and having been diagnosed with diabetes for at least 3 years. Considering co-morbidity, six participants had both type 2 diabetes and hypertension. Five women and one man were taking calcium channel blockers for the management of hypertension. Nine participants were taking insulin for the management of diabetes. Furthermore, participants were asked if they currently participated in planned exercise (defined as participation in physical activities for 30 minutes on three or more days of the week). One man and two women reported participation in physical activities. Eleven participants denied participation in physical activities. Individuals who smoked, consumed more than 4 alcoholic beverages a day, and had vascular or cardiovascular complications; liver or renal impairment, life threatening diseases, or orthopedic problems were excluded from the study. Procedures Each participant completed the Physical Activity Readiness Questionnaire and a survey to report exercise history and social behaviors, such as smoking and alcohol consumption. Qualified participants were scheduled for an initial assessment, which included a 5-minute resting ECG recording, measurements for body weight, body height, FG, SBP, DBP and RHR.The aforementioned measurements were taken at baseline and at the end of the study. Body height (cm) and body weight (kg) were measured by standard methods (18). After a 5-min rest, participants had their sitting blood pressure and RHR measured. Blood pressure was measured using an adult size manual sphygmomanometer cuff placed on the left arm. Finger prick capillary blood samples (approximately 15 µL from each participant) were obtained after fasting overnight using BD Ultra Fine TM 30-Gauge Lancets (Franklin Lakes, NJ, USA). The CardioChekTM (Polymer Technology Systems Inc., Indianapolis, IN, USA) device was used to analyze the samples. Participants were instructed to abstain from alcohol, caffeine and physical activity 24 hours before the ECG testing. Measurement of HRV was performed using the time domain analysis which is a general measure of autonomic nervous system balance. Even though there are six commonly used time domain measurements (18) for the purpose of this study HRV was assessed manually from calculation of the mean R-R interval and its standard deviation. Prior to testing, participants comfortably lay in a supine position for 10 min in a quiet, semi dark room. Resting supine 5 min beat- to-beat heart rate was collected between 6:00 am and 10:00 am. Lead II was selected to assess HRV before and after 12-weeks of training. ECG data was gathered on a Quinton Q4500 machine (Quinton Q4500 ®, Bothell, WA, USA) (19). Previous research has demonstrated that HRV measures obtained from a 5-min sample period using time domain analysis are highly stable over time (r=0.9) (20). Experimental Protocol One week prior to the beginning of the intervention, participants attended a familiarization session during which maximal heart rate (HR max) was estimated and exercise intensity was determined. The HR max was estimated using the formula 208 – (0.7 x age) (21). The target heart rate (THR) was calculated using the following formula: THR = [(HRmax − HRrest) × %Intensity)] + HRrest Patients followed a 12-week HIIT program on a treadmill consisting of four ~30 min sessions per week. A HIIT session involved a 3-minute warm-up period, six short (2 minutes) maximum-intensity (80-90% HR max) efforts separated by six moderate intensity (50-60% HR max) recovery intervals (2 minutes), and a 3-minute cool down period. Exercise intensity was modified until the THR was HRV and Type 2 Diabetes 26 reached. Inclination was kept at 1%. The workout was supervised and continuously monitored with a heart rate monitor (Omron HR100 ®). In addition, blood pressure was monitored before, during and after the workout sessions. Exercise intensity was lowered in cases where the blood pressure became elevated to 220/110 mmHg or higher, and was only resumed if blood pressure dropped below this value. In participants undergoing insulin therapy, the insulin dose was reduced before exercise. If hypoglycemia occurred during exercise, glucose dissolved in lukewarm water was taken. Participants received no dietary intervention; however, they were instructed not to change their eating habits during the course of the study. Furthermore, participants were encouraged to have a day off after 2 consecutive workouts. Statistical Analyses The SAS statistical software (version SAS 8.2) was used for the statistical analysis. Normality and homogeneity of variance assumptions were assessed. Paired samples t-test was used to analyze differences in HRV before and after the 12 weeks of training. Paired sample t-test was also used to determine differences in RHR, SBP, DBP, FG and body weight before and after 12-weeks of training. The level of significance was set at p = .05. RESULTS Participants performed 94 ± 3 % of the scheduled exercise sessions and no exercise- related injuries were reported. One incidence of hypoglycemia that occurred immediately post exercise was resolved with administration of glucose dissolved in lukewarm water. Two participants had an exercise session terminated due to elevated blood pressure. Based on Shapiro-Wilk test (p > Table 1. Physical Characteristics of individuals with type 2 diabetes before and following 12 weeks of training. 0.05) the normality assumption was Characteristics Pre Post met for all variables. Brown and Forsythe's test was used to test the Age(years) 57 6.7 57 6.7 homogeneity of variance. HRV (ms) 52.70 8.50 62.60 11.00* Homogeneity of variance assumption RHR(bpm) 76 9 69 9* was met for HRV measures (p > Body Weight (kg) 94.31 23.8 90.47 23.43* 0.05). Table 1 demonstrates the Resting SBP (mmHg) 134 11 127 9* physical characteristics of the Resting DBP (mmHg) 84 6 80.00 5* participants pre- and post training. Values are mean ± SD; Subjects (N=14); *p<0.05. Note: HRV: Heart Rate Variability, FG: Fasting Glucose; RHR: Resting Heart HRV was significantly greater Rate; SBP: Systolic Blood Pressure, DBP: Diastolic Blood following 12-weeks of training (p Pressure. <0.05). Mean SBP was significantly lower after 12-weeks of training, (p < 0.05). Similar results were identified for changes in DBP (p <0.05). Also, body weight was significantly lower post- compared to pre-training (p <0.05). Finally, RHR (p <0.05) and FG (p <0.05) values were significantly lower post- compared to pre training. DISCUSSION The goal of this project was to address the effect of HIIT on cardiovascular autonomic function as determined by HRV, in individuals with diabetes. Previous research has indicated that continuous aerobic training can result in significant improvements in HRV in individuals with diabetes (6, 22). Bhagyalakshmi and co-workers demonstrated a significant increase in HRV with increasing duration of exercise whereas HRV decreased in the control group. The investigators concluded that 30 HRV and Type 2 Diabetes 27 minutes of moderate intensity continuous cycling or treadmill exercise on most days of the week can significantly increase HRV in individuals with type 2 diabetes (6). Similarly, Pagkalos and colleagues (22) demonstrated that continuous treadmill exercise 3 times a week for six months (at 70% to 85% of heart rate reserve) can result in significant increase in HRV. The current study demonstrated that 12 weeks of HIIT can cause significant improvements in HRV suggesting that HIIT may be as effective as continuous aerobic exercise in improving cardiac autonomic function. Future research is warranted to examine whether individuals with diabetes find this training less monotonous, more motivating and enjoyable than continuous aerobic exercise. Since both RHR and HRV depend on the autonomic nervous system the two variables are not independent. Research indicated that RHR is a strong predictor of total mortality and mortality from a number of causes including diabetes (23, 24).The results of the current study indicated a significant reduction in RHR. The observed mean difference was 7 bpm. Similarly, Pagkalos and co-workers (22) demonstrated that RHR was reduced by 12.8% and 8% in individuals with diabetes with CAN and those without CAN, respectively. Thus, HIIT could be as effective as continuous exercise training in reducing RHR in individuals with diabetes. Previous research has indicated that continuous aerobic exercise training can result in reductions in blood pressure (25,26). Figueroa and colleagues (25) demonstrated that 16 weeks of moderate intensity continuous aerobic exercise resulted in 8% (p < 0.001) decrease in resting SBP in obese individuals with type 2 diabetes. Similarly, Hotta and colleagues (26) demonstrated that mean resting SBP decreased from 128.4 to 106.4 mmHg (p < 0.01) while DBP decreased from 78.2 to 66.0 mmHg (P < 0.01) in individuals with diabetes that followed a continuous aerobic exercise program for 3 weeks along with a low calorie diet. Similar to continuous aerobic exercise, interval training has been shown to reduce SBP and DBP in middle age and older individuals (27) and in individuals with metabolic syndrome (14). Similarly, the current study demonstrated that HIIT could be effective in reducing SBP and DBP in individuals with diabetes. Limitations For the purpose of this study HRV was assessed manually from the calculation of mean R-R interval and its standard deviation measured on the 5-minute ECG recording. The results of the current study should be viewed with caution since only two of the time domain measures were used for the determination of HRV. Moreover, both frequency and time domain measures should be used for a more accurate measurement of HRV. CONCLUSION The beneficial effect on autonomic regulation as a result of exercise training may have clinical importance in preventing adverse cardiovascular events in individuals with diabetes. Exercise and health care professionals could use this form of training as an alternative to continuous aerobic exercise to enhance participation and effectively manage diabetic complications. More data utilizing a larger sample of individuals with type 2 diabetes is needed to confirm the beneficial effects of HIIT on cardiovascular autonomic function. Address for correspondence: Koulla Parpa, Ph.D., Department of Health, Kinesiology, Recreation and Dance, University of Arkansas, Fayetteville, USA Email:firstname.lastname@example.org, email@example.com. HRV and Type 2 Diabetes 28 REFERENCES 1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. 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