Clin Auton Res DOI 10.1007/s10286-015-0291-0
SHORT COMMUNICATION
Inspiratory muscle training in patients with diabetic autonomic neuropathy: a randomized clinical trial Diogo Machado Kaminski1,2 • Beatriz D. Schaan1,3,4 • Antoˆnio Marcos Vargas da Silva5 • Pedro Paulo Soares6 • Pedro Dal Lago7
Received: 11 August 2014 / Accepted: 5 March 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Aims and methods We evaluated the effects of an 8-week inspiratory muscle training (IMT, n = 5) or placebo IMT (P-IMT, n = 5) on maximal respiratory pressures, pulmonary function, functional capacity, and cardiac autonomic control in patients with type 2 diabetes and diabetic autonomic neuropathy (DAN). Results and conclusions The IMT group had a greater increase in maximum inspiratory pressure as compared to P-IMT (p \ 0.05). The IMT improved inspiratory muscle strength in patients with DAN.
Introduction
1
Hospital de Clı´nicas de Porto Alegre, Porto Alegre, RS, Brazil
2
Instituto de Cardiologia/Fundac¸a˜o, Universita´ria de Cardiologia do Rio Grande do Sul, Porto Alegre, RS, Brazil
Diabetic autonomic neuropathy (DAN) causes significant morbidity and mortality [5]. It is usually diagnosed using the classic cardiovascular autonomic tests described by Ewing [6], but analysis of heart rate variability (HRV) can also evaluate sympathetic and parasympathetic modulation of heart rate [10]. Pulmonary function abnormalities, such as reduction in forced vital capacity (FVC), forced expiratory volume in one second (FEV1) [13], inspiratory muscle strength [3, 8] and ventilatory muscle endurance were also described [8] in patients with type 2 diabetes, irrespective of the presence of DAN. Since inspiratory muscle training can be beneficial to diabetic patients with inspiratory muscle weakness [3], we hypothesized that it would also be useful for patients with DAN. Inspiratory muscle training has also been shown to improve autonomic modulation in patients with hyperrtension [7] and heart failure [11]. The purpose of this study was to evaluate the effects of inspiratory muscle training on maximal respiratory pressures, pulmonary function, functional capacity, and cardiac autonomic control, in patients with cardiovascular DAN.
3
Servic¸o de Endocrinologia, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, pre´dio 12, 48 andar, Porto Alegre, RS, Brazil
Methods
Keywords Diabetes mellitus type 2 Diabetic neuropathies Autonomic nervous system Inspiratory muscle training
& Beatriz D. Schaan [email protected]
4
Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
5
Department of Physiotherapy and Rehabilitation, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
6
Universidade Federal Fluminense, Nitero´i, RJ, Brazil
7
Universidade Federal de Cieˆncias da Sau´de de Porto Alegre, Porto Alegre, RS, Brazil
This randomized controlled clinical trial was conducted in patients with type 2 diabetes and cardiovascular DAN (one or more Ewing positive tests) [6, 12], who were recruited from a tertiary general hospital. The primary outcome was maximal inspiratory pressure, and the secondary outcomes were changes in cardiovascular autonomic control indexes, pulmonary function, and functional capacity. Subjects who
123
Clin Auton Res
satisfied the inclusion criteria had a diagnosis of type 2 diabetes and cardiovascular DAN, and were between the ages of 35 and 69 years old. Exclusion criteria were heart failure, class III obesity, chronic obstructive pulmonary disease, exercise-induced asthma, and/or current smoking habit. The protocol was previously registered with (NCT00752440) and approved by the research ethics committees of the involved institutions. All subjects gave informed consent. Eligible subjects were randomly assigned by electronic randomization to the inspiratory muscle training group (IMT) or to the placebo group (PIMT) for 8 weeks. Measurements of maximal respiratory pressures, pulmonary function, functional capacity, and cardiovascular autonomic function were taken before and after the intervention. The diagnosis of DAN was confirmed using the Ewing autonomic function tests, as previously described [5] and standardized in our institution [12]. Patients were classified according to the number of abnormal tests. An electrocardiogram tracing (Biopac MP-150, California, USA) was obtained for 15 min and the RR time series were evaluated in the time and frequency domain [7]. Maximal respiratory pressures were evaluated through measurements of maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax), as previously described [4]. The results were expressed as absolute values and percentage of predicted. Pulmonary function was evaluated with a spirometer (Minispir-Medical International Research, Rome, Italy). Measurements of FVC, FEV1, FEV1/FVC, peak expiratory flow (PEF), and inspiratory capacity before and after the use of a bronchodilator (400 lg salbutamol) were obtained. Functional capacity and ventilatory efficiency were evaluated by maximal cardiopulmonary exercise test, using a bicycle ergometer with electromagnetic braking (Inbrasport, Porto Alegre, Brazil), a 12-lead electrocardiogram (Apex 2000, Inbramed, Porto Alegre, Brazil) and a metabolic gas analyzer (VO2000, Inbrasport) [7]. Inspiratory muscle training was performed using a linear pressure resistance device (ThresholdÒ, New Jersey, USA), for a period of 8 weeks, 7 days/week, 30 min/day as described [4].
Statistical analysis Descriptive data are presented as mean ± SD. Characteristics were compared by the Student’s t test, Mann–Whitney test, or Fischer’s exact test. The effect of the intervention was analyzed by the two-way analysis of variance for repeated measurements (ANOVA) followed by the Tukey post hoc test, and by comparing the deltas (variation between post and pre) using the Mann–Whitney
123
test. A p value \0.05 was considered significant. Software statistical package for social sciences (SPSS version 13.0 for Windows) was used.
Results One hundred and fifty patients were selected from our medical records; 65 declined the invitation, 20 did not attend scheduled appointments, and 25 could not be contacted, leaving 40 patients for evaluation. From these, seven could not be evaluated with the Ewing tests, four did not have DAN, 3 had other exclusion criteria, and 13 abandoned the study. The 12 remaining patients were classified as having incipient (n = 5), moderate (n = 5), or severe (n = 2) cardiovascular DAN, and were then randomized; two of them abandoned the study after randomization, and 10 completed the protocol. Baseline clinical characteristics were similar between groups: age was 56 ± 9 vs. 55 ± 10 years, duration of diabetes was 13 ± 1 vs. 10.7 ± 6 years, severity of cardiovascular DAN, blood pressure levels, glycemia, glycated hemoglobin, creatinine, and lipids. The groups were also similar with respect to respiratory muscle strength, and inspiratory muscle weakness was present in only two patients of the IMT group at baseline. Table 1 shows respiratory muscle strength, pulmonary function, and functional capacity at baseline and after training in the groups evaluated. Inspiratory muscle training resulted in higher PImax levels after 8 weeks; the delta of this variable was greater in the IMT group (49 ± 39 cmH2O) as compared to the P-IMT group (14 ± 12 cmH2O), p = 0.05. Table 2 shows heart rate variability in the time and frequency domains in the groups studied, expressed as delta variation, showing a decrease of the LFn component in the IMT as compared with the P-IMT group.
Discussion We demonstrated that inspiratory muscle training was effective in improving the strength of the inspiratory muscles and in reducing the LFn component of heart rate variability in patients with DAN irrespective of them having or not having muscle weakness, but it had no effect on lung function and functional capacity. The adaptive change in inspiratory muscles (36 % increase in inspiratory muscle strength) probably represents an increased thickness of the diaphragm [2]. Prior studies in heart failure patients with inspiratory muscle weakness showed a greater increase in PImax than presented here [2, 4]. These differences are probably due to the distinct
Clin Auton Res Table 1 Respiratory muscle strength, pulmonary function, and functional capacity in P-IMT and IMT groups before and after intervention P-IMT (n = 5) Before PImax (-cmH2O)
IMT (n = 5) After
Before
P value After
Time
Group
Interaction
98 ± 34
112 ± 23
88 ± 26
137 ± 27*
0.01
0.61
0.09
102 ± 26
118 ± 21
88 ± 28
141 ± 51*
0.02
0.80
0.16
98 ± 35
105 ± 27
111 ± 16
111 ± 24
0.47
0.62
0.47
PEmax (% of predicted)
100 ± 16
108 ± 13
111 ± 30
109 ± 26
0.48
0.67
0.29
FVC (% of predicted)
100 ± 12
96 ± 10
93 ± 07
98 ± 11
0.99
0.67
0.99
FEV1 (% of predicted)
97 ± 13
98 ± 18
95 ± 10
98 ± 14
0.36
0.90
0.43
FEV1/FVC (% of predicted) PEF (% of predicted)
97 ± 03 95 ± 11
100 ± 06 95 ± 17
98 ± 10 91 ± 15
100 ± 06 98 ± 10
0.17 0.26
0.92 1.00
0.95 0.29
PImax (% of predicted) PEmax (cmH2O)
Inspiratory capacity (% of predicted)
89 ± 17
91 ± 09
71 ± 15
88 ± 16
0.13
0.19
0.21
Peak VO2 (ml/kg.min)
24 ± 07
20 ± 03
26 ± 03
26 ± 03
0.25
0.18
0.12
Peak VO2 (% of predicted)
81 ± 28
66 ± 14
79 ± 21
83 ± 24
0.28
0.61
0.10
VE/VO2
20 ± 02
22 ± 03
20 ± 03
21 ± 04
0.36
0.59
0.75
VE/VCO2
23 ± 01
25 ± 04
25 ± 03
22 ± 01
0.57
0.52
0.06
Values are expressed as mean ± SD IMT inspiratory muscle training group, P-IMT inspiratory muscle training placebo group, PImax maximum inspiratory pressure, PEmax maximum expiratory pressure, FVC forced vital capacity, FEV1 forced expiratory volume in one second, FEV1% percentage of FEV1 expired in one second, PEF peak expiratory flow, VO2 maximal oxygen uptake, VE/VO2 ventilatory equivalent for oxygen, and VE/VCO2 ventilatory equivalent for carbon dioxide * p \ 0.05 for comparison with before by Tukey post hoc test
Table 2 Heart rate variability in the time and frequency domain in P-IMT and IMT groups, expressed as difference between before and after intervention P-IMT (n = 5)
IMT (n = 5)
P value
Time domain RR (ms) RRsd (ms) rMSSD (ms) HR (bpm)
83 ± 40
96 ± 134
0.41
5±4 5±6
5±4 3±4
0.90 0.41
-8 ± 3
-5 ± 10
0.29 0.73
Frequency domain Var (ms2)
152 ± 730
430 ± 594
TP (ms2 Hz-1)
98 ± 236
172 ± 209
0.29
LF (ms2)
31 ± 52
9 ± 15
0.90
HF (ms2)
78 ± 108
47 ± 87
0.41
LFn (n.u.)
6±2
-3 ± 4
0.02
HFn (n.u.) LF/HF (ratio)
20 ± 8 -0.1 ± 0.2
1 ± 10
0.06
-0.2 ± 0.2
0.19
Values of delta are expressed as mean ± SD Mann–Whitney test: p \ 0.05 for comparison of the deltas IMT inspiratory muscle training group, P-IMT inspiratory muscle training placebo group, RR mean RR interval, RRsd standard deviation of RR intervals, rMSSD square root of the mean differences between consecutive high-squared RR intervals, HR heart rate, Var variance of RR intervals, TP total power, LF low frequency power, HF high frequency power, LFn normalized unit of low frequency power, HFn normalized unit of high frequency power, LF/HF relationship between low frequency and high frequency
characteristics of the primary disease. Inspiratory muscle weakness at baseline was an inclusion criteria in these previous studies, perhaps potentiating the improvement of PImax and, therefore, the effectiveness of inspiratory muscle training. The same explanation can be applied to the fact that a 119 % increase in PImax after inspiratory muscle training was previously shown in patients with diabetes, irrespective of them having or not autonomic neuropathy— these patients had muscle weakness previous to engaging on the training [3]. The decrease respiratory muscle strength in type 2 diabetes can be explained by impaired respiratory neuromuscular function caused by polyneuropathy [9]. It is noteworthy that even in cases with no inspiratory muscle weakness prior to training, the inspiratory muscle training was able to increase the PImax. Considering cardiovascular autonomic evaluation, the reduction in the LFn component of heart rate variability suggests a decreased sympathetic cardiac modulation induced by the inspiratory training. This reduction in LFn component was accompanied by an increase in the LFn component in the P-IMT group, which probably explains the significant results that we found. The positive effects of inspiratory muscle training previously described in hypertensive patients (increased parasympathetic modulation, reduced sympathetic modulation, and reduced cardiac sympathetic discharge) probably occurred because of the concomitant reduction in blood pressure [7]. The high
123
Clin Auton Res
variability observed in our results, in consideration with the small number of individuals evaluated, could overestimate the observation of a possible positive result. Moreover, given that subjects on the P-IMT group were leaner (data not shown), the inspiratory muscle training could have improved sleep apnea among the intervention training group and this would change autonomic modulation [1]. A limitation of the study is the small sample size. In conclusion, an 8-week inspiratory muscle training program can improve the inspiratory muscle strength and modulate autonomic function in patients with DAN.
References 1. Arikan H, Bellur N, Caliskan H, Saglam M, Vardar-Yagli N, Calik E, Inal-Ince D, Savci S, Yuce Ege M, Firat H, Ardic S (2012) Inspiratory muscle training in obstructive sleep apnea syndrome. Eur Respir J 40 2. Chiappa GR, Roseguini BT, Vieira PJ, Alves CN, Tavares A, Winkelmann ER, Ferlin EL, Stein R, Ribeiro JP (2008) Inspiratory muscle training improves blood flow to resting and exercising limbs in patients with chronic heart failure. J Am Coll Cardiol 51:1663–1671 3. Correa AP, Ribeiro JP, Balzan FM, Mundstock L, Ferlin EL, Moraes RS (2011) Inspiratory muscle training in type 2 diabetes with inspiratory muscle weakness. Med Sci Sports Exerc 43:1135–1141 4. Dall’Ago P, Chiappa GR, Guths H, Stein R, Ribeiro JP (2006) Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: a randomized trial. J Am Coll Cardiol 47:757–763
123
5. Ewing DJ, Campbell IW, Clarke BF (1980) The natural history of diabetic autonomic neuropathy. Q J Med 49:95–108 6. Ewing DJ, Clarke BF (1982) Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed) 285:916–918 7. Ferreira JB, Plentz RD, Stein C, Casali KR, Arena R, Lago PD (2013) Inspiratory muscle training reduces blood pressure and sympathetic activity in hypertensive patients: a randomized controlled trial. Int J Cardiol 166:61–67 8. Fuso L, Pitocco D, Longobardi A, Zaccardi F, Contu C, Pozzuto C, Basso S, Varone F, Ghirlanda G, Antonelli Incalzi R (2012) Reduced respiratory muscle strength and endurance in type 2 diabetes mellitus. Diabetes Metab Res Rev 28:370–375 9. Kabitz HJ, Sonntag F, Walker D, Schwoerer A, Walterspacher S, Kaufmann S, Beuschlein F, Seufert J, Windisch W (2008) Diabetic polyneuropathy is associated with respiratory muscle impairment in type 2 diabetes. Diabetologia 51:191–197 10. Lahiri MK, Kannankeril PJ, Goldberger JJ (2008) Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol 51:1725–1733 11. Mello PR, Guerra GM, Borile S, Rondon MU, Alves MJ, Negrao CE, Dal Lago P, Mostarda C, Irigoyen MC, Consolim-Colombo FM (2012) Inspiratory muscle training reduces sympathetic nervous activity and improves inspiratory muscle weakness and quality of life in patients with chronic heart failure: a clinical trial. J Cardiopulm Rehabil Prev 32:255–261 12. Neumann C, Schmid H (1997) Standardization of a computerized method for calculating autonomic function test responses in healthy subjects and patients with diabetes mellitus. Braz J Med Biol Res 30:197–205 13. Yeh HC, Punjabi NM, Wang NY, Pankow JS, Duncan BB, Cox CE, Selvin E, Brancati FL (2008) Cross-sectional and prospective study of lung function in adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 31:741–746
SHORT COMMUNICATION
Inspiratory muscle training in patients with diabetic autonomic neuropathy: a randomized clinical trial Diogo Machado Kaminski1,2 • Beatriz D. Schaan1,3,4 • Antoˆnio Marcos Vargas da Silva5 • Pedro Paulo Soares6 • Pedro Dal Lago7
Received: 11 August 2014 / Accepted: 5 March 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Aims and methods We evaluated the effects of an 8-week inspiratory muscle training (IMT, n = 5) or placebo IMT (P-IMT, n = 5) on maximal respiratory pressures, pulmonary function, functional capacity, and cardiac autonomic control in patients with type 2 diabetes and diabetic autonomic neuropathy (DAN). Results and conclusions The IMT group had a greater increase in maximum inspiratory pressure as compared to P-IMT (p \ 0.05). The IMT improved inspiratory muscle strength in patients with DAN.
Introduction
1
Hospital de Clı´nicas de Porto Alegre, Porto Alegre, RS, Brazil
2
Instituto de Cardiologia/Fundac¸a˜o, Universita´ria de Cardiologia do Rio Grande do Sul, Porto Alegre, RS, Brazil
Diabetic autonomic neuropathy (DAN) causes significant morbidity and mortality [5]. It is usually diagnosed using the classic cardiovascular autonomic tests described by Ewing [6], but analysis of heart rate variability (HRV) can also evaluate sympathetic and parasympathetic modulation of heart rate [10]. Pulmonary function abnormalities, such as reduction in forced vital capacity (FVC), forced expiratory volume in one second (FEV1) [13], inspiratory muscle strength [3, 8] and ventilatory muscle endurance were also described [8] in patients with type 2 diabetes, irrespective of the presence of DAN. Since inspiratory muscle training can be beneficial to diabetic patients with inspiratory muscle weakness [3], we hypothesized that it would also be useful for patients with DAN. Inspiratory muscle training has also been shown to improve autonomic modulation in patients with hyperrtension [7] and heart failure [11]. The purpose of this study was to evaluate the effects of inspiratory muscle training on maximal respiratory pressures, pulmonary function, functional capacity, and cardiac autonomic control, in patients with cardiovascular DAN.
3
Servic¸o de Endocrinologia, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, pre´dio 12, 48 andar, Porto Alegre, RS, Brazil
Methods
Keywords Diabetes mellitus type 2 Diabetic neuropathies Autonomic nervous system Inspiratory muscle training
& Beatriz D. Schaan [email protected]
4
Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
5
Department of Physiotherapy and Rehabilitation, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
6
Universidade Federal Fluminense, Nitero´i, RJ, Brazil
7
Universidade Federal de Cieˆncias da Sau´de de Porto Alegre, Porto Alegre, RS, Brazil
This randomized controlled clinical trial was conducted in patients with type 2 diabetes and cardiovascular DAN (one or more Ewing positive tests) [6, 12], who were recruited from a tertiary general hospital. The primary outcome was maximal inspiratory pressure, and the secondary outcomes were changes in cardiovascular autonomic control indexes, pulmonary function, and functional capacity. Subjects who
123
Clin Auton Res
satisfied the inclusion criteria had a diagnosis of type 2 diabetes and cardiovascular DAN, and were between the ages of 35 and 69 years old. Exclusion criteria were heart failure, class III obesity, chronic obstructive pulmonary disease, exercise-induced asthma, and/or current smoking habit. The protocol was previously registered with (NCT00752440) and approved by the research ethics committees of the involved institutions. All subjects gave informed consent. Eligible subjects were randomly assigned by electronic randomization to the inspiratory muscle training group (IMT) or to the placebo group (PIMT) for 8 weeks. Measurements of maximal respiratory pressures, pulmonary function, functional capacity, and cardiovascular autonomic function were taken before and after the intervention. The diagnosis of DAN was confirmed using the Ewing autonomic function tests, as previously described [5] and standardized in our institution [12]. Patients were classified according to the number of abnormal tests. An electrocardiogram tracing (Biopac MP-150, California, USA) was obtained for 15 min and the RR time series were evaluated in the time and frequency domain [7]. Maximal respiratory pressures were evaluated through measurements of maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax), as previously described [4]. The results were expressed as absolute values and percentage of predicted. Pulmonary function was evaluated with a spirometer (Minispir-Medical International Research, Rome, Italy). Measurements of FVC, FEV1, FEV1/FVC, peak expiratory flow (PEF), and inspiratory capacity before and after the use of a bronchodilator (400 lg salbutamol) were obtained. Functional capacity and ventilatory efficiency were evaluated by maximal cardiopulmonary exercise test, using a bicycle ergometer with electromagnetic braking (Inbrasport, Porto Alegre, Brazil), a 12-lead electrocardiogram (Apex 2000, Inbramed, Porto Alegre, Brazil) and a metabolic gas analyzer (VO2000, Inbrasport) [7]. Inspiratory muscle training was performed using a linear pressure resistance device (ThresholdÒ, New Jersey, USA), for a period of 8 weeks, 7 days/week, 30 min/day as described [4].
Statistical analysis Descriptive data are presented as mean ± SD. Characteristics were compared by the Student’s t test, Mann–Whitney test, or Fischer’s exact test. The effect of the intervention was analyzed by the two-way analysis of variance for repeated measurements (ANOVA) followed by the Tukey post hoc test, and by comparing the deltas (variation between post and pre) using the Mann–Whitney
123
test. A p value \0.05 was considered significant. Software statistical package for social sciences (SPSS version 13.0 for Windows) was used.
Results One hundred and fifty patients were selected from our medical records; 65 declined the invitation, 20 did not attend scheduled appointments, and 25 could not be contacted, leaving 40 patients for evaluation. From these, seven could not be evaluated with the Ewing tests, four did not have DAN, 3 had other exclusion criteria, and 13 abandoned the study. The 12 remaining patients were classified as having incipient (n = 5), moderate (n = 5), or severe (n = 2) cardiovascular DAN, and were then randomized; two of them abandoned the study after randomization, and 10 completed the protocol. Baseline clinical characteristics were similar between groups: age was 56 ± 9 vs. 55 ± 10 years, duration of diabetes was 13 ± 1 vs. 10.7 ± 6 years, severity of cardiovascular DAN, blood pressure levels, glycemia, glycated hemoglobin, creatinine, and lipids. The groups were also similar with respect to respiratory muscle strength, and inspiratory muscle weakness was present in only two patients of the IMT group at baseline. Table 1 shows respiratory muscle strength, pulmonary function, and functional capacity at baseline and after training in the groups evaluated. Inspiratory muscle training resulted in higher PImax levels after 8 weeks; the delta of this variable was greater in the IMT group (49 ± 39 cmH2O) as compared to the P-IMT group (14 ± 12 cmH2O), p = 0.05. Table 2 shows heart rate variability in the time and frequency domains in the groups studied, expressed as delta variation, showing a decrease of the LFn component in the IMT as compared with the P-IMT group.
Discussion We demonstrated that inspiratory muscle training was effective in improving the strength of the inspiratory muscles and in reducing the LFn component of heart rate variability in patients with DAN irrespective of them having or not having muscle weakness, but it had no effect on lung function and functional capacity. The adaptive change in inspiratory muscles (36 % increase in inspiratory muscle strength) probably represents an increased thickness of the diaphragm [2]. Prior studies in heart failure patients with inspiratory muscle weakness showed a greater increase in PImax than presented here [2, 4]. These differences are probably due to the distinct
Clin Auton Res Table 1 Respiratory muscle strength, pulmonary function, and functional capacity in P-IMT and IMT groups before and after intervention P-IMT (n = 5) Before PImax (-cmH2O)
IMT (n = 5) After
Before
P value After
Time
Group
Interaction
98 ± 34
112 ± 23
88 ± 26
137 ± 27*
0.01
0.61
0.09
102 ± 26
118 ± 21
88 ± 28
141 ± 51*
0.02
0.80
0.16
98 ± 35
105 ± 27
111 ± 16
111 ± 24
0.47
0.62
0.47
PEmax (% of predicted)
100 ± 16
108 ± 13
111 ± 30
109 ± 26
0.48
0.67
0.29
FVC (% of predicted)
100 ± 12
96 ± 10
93 ± 07
98 ± 11
0.99
0.67
0.99
FEV1 (% of predicted)
97 ± 13
98 ± 18
95 ± 10
98 ± 14
0.36
0.90
0.43
FEV1/FVC (% of predicted) PEF (% of predicted)
97 ± 03 95 ± 11
100 ± 06 95 ± 17
98 ± 10 91 ± 15
100 ± 06 98 ± 10
0.17 0.26
0.92 1.00
0.95 0.29
PImax (% of predicted) PEmax (cmH2O)
Inspiratory capacity (% of predicted)
89 ± 17
91 ± 09
71 ± 15
88 ± 16
0.13
0.19
0.21
Peak VO2 (ml/kg.min)
24 ± 07
20 ± 03
26 ± 03
26 ± 03
0.25
0.18
0.12
Peak VO2 (% of predicted)
81 ± 28
66 ± 14
79 ± 21
83 ± 24
0.28
0.61
0.10
VE/VO2
20 ± 02
22 ± 03
20 ± 03
21 ± 04
0.36
0.59
0.75
VE/VCO2
23 ± 01
25 ± 04
25 ± 03
22 ± 01
0.57
0.52
0.06
Values are expressed as mean ± SD IMT inspiratory muscle training group, P-IMT inspiratory muscle training placebo group, PImax maximum inspiratory pressure, PEmax maximum expiratory pressure, FVC forced vital capacity, FEV1 forced expiratory volume in one second, FEV1% percentage of FEV1 expired in one second, PEF peak expiratory flow, VO2 maximal oxygen uptake, VE/VO2 ventilatory equivalent for oxygen, and VE/VCO2 ventilatory equivalent for carbon dioxide * p \ 0.05 for comparison with before by Tukey post hoc test
Table 2 Heart rate variability in the time and frequency domain in P-IMT and IMT groups, expressed as difference between before and after intervention P-IMT (n = 5)
IMT (n = 5)
P value
Time domain RR (ms) RRsd (ms) rMSSD (ms) HR (bpm)
83 ± 40
96 ± 134
0.41
5±4 5±6
5±4 3±4
0.90 0.41
-8 ± 3
-5 ± 10
0.29 0.73
Frequency domain Var (ms2)
152 ± 730
430 ± 594
TP (ms2 Hz-1)
98 ± 236
172 ± 209
0.29
LF (ms2)
31 ± 52
9 ± 15
0.90
HF (ms2)
78 ± 108
47 ± 87
0.41
LFn (n.u.)
6±2
-3 ± 4
0.02
HFn (n.u.) LF/HF (ratio)
20 ± 8 -0.1 ± 0.2
1 ± 10
0.06
-0.2 ± 0.2
0.19
Values of delta are expressed as mean ± SD Mann–Whitney test: p \ 0.05 for comparison of the deltas IMT inspiratory muscle training group, P-IMT inspiratory muscle training placebo group, RR mean RR interval, RRsd standard deviation of RR intervals, rMSSD square root of the mean differences between consecutive high-squared RR intervals, HR heart rate, Var variance of RR intervals, TP total power, LF low frequency power, HF high frequency power, LFn normalized unit of low frequency power, HFn normalized unit of high frequency power, LF/HF relationship between low frequency and high frequency
characteristics of the primary disease. Inspiratory muscle weakness at baseline was an inclusion criteria in these previous studies, perhaps potentiating the improvement of PImax and, therefore, the effectiveness of inspiratory muscle training. The same explanation can be applied to the fact that a 119 % increase in PImax after inspiratory muscle training was previously shown in patients with diabetes, irrespective of them having or not autonomic neuropathy— these patients had muscle weakness previous to engaging on the training [3]. The decrease respiratory muscle strength in type 2 diabetes can be explained by impaired respiratory neuromuscular function caused by polyneuropathy [9]. It is noteworthy that even in cases with no inspiratory muscle weakness prior to training, the inspiratory muscle training was able to increase the PImax. Considering cardiovascular autonomic evaluation, the reduction in the LFn component of heart rate variability suggests a decreased sympathetic cardiac modulation induced by the inspiratory training. This reduction in LFn component was accompanied by an increase in the LFn component in the P-IMT group, which probably explains the significant results that we found. The positive effects of inspiratory muscle training previously described in hypertensive patients (increased parasympathetic modulation, reduced sympathetic modulation, and reduced cardiac sympathetic discharge) probably occurred because of the concomitant reduction in blood pressure [7]. The high
123
Clin Auton Res
variability observed in our results, in consideration with the small number of individuals evaluated, could overestimate the observation of a possible positive result. Moreover, given that subjects on the P-IMT group were leaner (data not shown), the inspiratory muscle training could have improved sleep apnea among the intervention training group and this would change autonomic modulation [1]. A limitation of the study is the small sample size. In conclusion, an 8-week inspiratory muscle training program can improve the inspiratory muscle strength and modulate autonomic function in patients with DAN.
References 1. Arikan H, Bellur N, Caliskan H, Saglam M, Vardar-Yagli N, Calik E, Inal-Ince D, Savci S, Yuce Ege M, Firat H, Ardic S (2012) Inspiratory muscle training in obstructive sleep apnea syndrome. Eur Respir J 40 2. Chiappa GR, Roseguini BT, Vieira PJ, Alves CN, Tavares A, Winkelmann ER, Ferlin EL, Stein R, Ribeiro JP (2008) Inspiratory muscle training improves blood flow to resting and exercising limbs in patients with chronic heart failure. J Am Coll Cardiol 51:1663–1671 3. Correa AP, Ribeiro JP, Balzan FM, Mundstock L, Ferlin EL, Moraes RS (2011) Inspiratory muscle training in type 2 diabetes with inspiratory muscle weakness. Med Sci Sports Exerc 43:1135–1141 4. Dall’Ago P, Chiappa GR, Guths H, Stein R, Ribeiro JP (2006) Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: a randomized trial. J Am Coll Cardiol 47:757–763
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5. Ewing DJ, Campbell IW, Clarke BF (1980) The natural history of diabetic autonomic neuropathy. Q J Med 49:95–108 6. Ewing DJ, Clarke BF (1982) Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed) 285:916–918 7. Ferreira JB, Plentz RD, Stein C, Casali KR, Arena R, Lago PD (2013) Inspiratory muscle training reduces blood pressure and sympathetic activity in hypertensive patients: a randomized controlled trial. Int J Cardiol 166:61–67 8. Fuso L, Pitocco D, Longobardi A, Zaccardi F, Contu C, Pozzuto C, Basso S, Varone F, Ghirlanda G, Antonelli Incalzi R (2012) Reduced respiratory muscle strength and endurance in type 2 diabetes mellitus. Diabetes Metab Res Rev 28:370–375 9. Kabitz HJ, Sonntag F, Walker D, Schwoerer A, Walterspacher S, Kaufmann S, Beuschlein F, Seufert J, Windisch W (2008) Diabetic polyneuropathy is associated with respiratory muscle impairment in type 2 diabetes. Diabetologia 51:191–197 10. Lahiri MK, Kannankeril PJ, Goldberger JJ (2008) Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol 51:1725–1733 11. Mello PR, Guerra GM, Borile S, Rondon MU, Alves MJ, Negrao CE, Dal Lago P, Mostarda C, Irigoyen MC, Consolim-Colombo FM (2012) Inspiratory muscle training reduces sympathetic nervous activity and improves inspiratory muscle weakness and quality of life in patients with chronic heart failure: a clinical trial. J Cardiopulm Rehabil Prev 32:255–261 12. Neumann C, Schmid H (1997) Standardization of a computerized method for calculating autonomic function test responses in healthy subjects and patients with diabetes mellitus. Braz J Med Biol Res 30:197–205 13. Yeh HC, Punjabi NM, Wang NY, Pankow JS, Duncan BB, Cox CE, Selvin E, Brancati FL (2008) Cross-sectional and prospective study of lung function in adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 31:741–746
