Download Elevated peak exercise systolic blood pressure is not associated

J Appl Physiol 101: 893– 897, 2006.
First published May 25, 2006; doi:10.1152/japplphysiol.00260.2006.
Elevated peak exercise systolic blood pressure is not associated with reduced
exercise capacity in subjects with Type 2 diabetes
Patrice Brassard, Annie Ferland, Valérie Gaudreault, Nadine Bonneville, Jean Jobin, and Paul Poirier
Institut Universitaire de Cardiologie et de Pneumologie, Centre de
Recherche de l’Hôpital Laval, Université Laval, Québec, Canada
Submitted 28 February 2006; accepted in final form 24 May 2006
peak oxygen uptake; Type 2 diabetic patients; high blood pressure
response
THE STUDY OF OXYGEN UPTAKE (V̇O2) during an incremental
exercise protocol reflects the integration of numerous body
functions in response to an imposed work stimulus (28). The
V̇O2 measured at maximal exercise, i.e., maximal or peak V̇O2
(V̇O2 max or V̇O2 peak), is very important in clinical practice
because it is related to survival (19). In subjects with Type 2
diabetes, a reduced V̇O2 max has been reported compared with
nondiabetic subjects (23, 24). However, the mechanisms responsible for this phenomenon remain unclear. Presence of
endothelial dysfunction (10, 27) and abnormalities of cardiac
function such as diastolic dysfunction (21) may be related to
this reduced exercise capacity. Furthermore, subtle hemodynamic changes in response to exercise appearing early in the
time course of diabetes might also have a negative influence on
exercise capacity.
Address for reprint requests and other correspondence: P. Poirier, Institut
Universitaire de Cardiologie et de Pneumologie, Centre de Recherche Clinique/Hôpital Laval, 2725 Chemin Ste-Foy, Sainte-Foy, Québec, Canada G1V
4G5 (e-mail: [email protected]).
http://www. jap.org
Type 2 diabetes is related to arterial stiffness (6), which in
turn is associated with increased afterload (6), leading to an
elevated systolic blood pressure (SBP) (4). An exaggerated
SBP response to exercise is associated with a lower cardiorespiratory fitness level in women (12). In contrast, athletes are
known to develop an elevated blood pressure (BP) response in
association with a higher exercise capacity compared with
nonathletes (9). In fact, a positive relationship between the
exercise BP response and left ventricular (LV) mass has been
documented in this population (9). However, the influence of
early hemodynamic changes induced by diabetes, such as the
presence of an elevated exercise SBP response on exercise
capacity in subjects with Type 2 diabetes without cardiovascular disease, is unknown.
The aim of the present study was to evaluate the impact of
an elevated SBP in response to peak exercise on different
parameters related to exercise capacity in sedentary subjects
with Type 2 diabetes without cardiovascular disease. We
hypothesized that subjects with higher exercise SBP would
have a reduced exercise capacity.
MATERIALS AND METHODS
Study Population
Twenty-eight sedentary men with Type 2 diabetes were recruited
for this study. All subjects had Type 2 diabetes treated with oral
hypoglycemic agents (metformin, glyburide, glyclazide) and/or diet.
No subject was on insulin. Exclusion criteria were a documented
presence of cardiovascular disease and hypertension, all forms of
complications related to diabetes and cardiovascular related medication. No subject presented macroalbuminuria. The study was approved by the local hospital ethics committee in accordance with the
Declaration of Helsinki, and all subject gave signed informed consent.
Evaluations
Blood sampling. At subjects’ arrival at the laboratory, a 18-gauge
polyethylene catheter was inserted into a forearm vein for blood
sampling. Blood samples were drawn at rest from subjects 30 min
before the exercise protocol for the measurement of fasting blood
glucose (FBG) and glycated hemoglobin (HbA1c), after an 8-h overnight fast. FBG was assayed using the hexokinase method (Roche
Diagnosis, Indianapolis, IN). HbA1c was assayed using the ionexchange high-performance liquid chromatography method (Bio-Rad,
Hercules, CA).
Exercise protocol. Exercise capacity was evaluated for each subject
using an incremental protocol of 15 W/min after a warm-up period of
1 min at 15 W and 2 min at 30 W, performed on an electromagnetically braked cycle ergometer (Corival, Lode, The Netherlands) at a
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8750-7587/06 $8.00 Copyright © 2006 the American Physiological Society
893
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Brassard, Patrice, Annie Ferland, Valérie Gaudreault, Nadine
Bonneville, Jean Jobin, and Paul Poirier. Elevated peak exercise
systolic blood pressure is not associated with reduced exercise capacity in
subjects with Type 2 diabetes. J Appl Physiol 101: 893– 897, 2006. First
published May 25, 2006; doi:10.1152/japplphysiol.00260.2006.—Subjects with Type 2 diabetes without cardiovascular disease have a reduced
exercise capacity compared with nondiabetic subjects. However, the
mechanisms responsible for this phenomenon are unknown. The purpose
of this study was to evaluate the impact of exercise systolic blood
pressure (SBP) response on diverse exercise tolerance parameters in Type
2 diabetic subjects. Twenty-eight sedentary men with Type 2 diabetes
were recruited for this study. Subjects were treated with oral hypoglycemic agents and/or diet. Evaluation of glycemic control and peak exercise
capacity were performed for each subject. The subjects were divided into
two groups according to the median value of peak SBP (210 mmHg)
measured in each subject. We observed a 13, 13, and 16% reduction in
the relative peak oxygen uptake (V̇O2 peak), absolute V̇O2 peak, and peak
work rate in the low- compared with the high-peak SBP group [26.95 (SD
5.35) vs. 30.96 (SD 3.61) ml䡠kg⫺1 䡠min⫺1, 2.5 (SD 0.4) vs. 2.8 (SD 0.6)
l/min, and 169 (SD 34) vs. 202 (SD 32) W; all P ⬍ 0.05]. After adjusting
for age, relative V̇O2 peak was still significantly different (P ⬍ 0.05). There
were similar peak respiratory exchange ratio (RER) [1.20 (SD 0.08) vs.
1.16 (SD 0.07); P ⫽ 0.24] and peak heart rate [160 (SD 20) vs. 169 (SD
15) beats/min; P ⫽ 0.18] between the low- compared with the high-SBP
group. No difference in glycemic control was observed between the two
groups. The results reported in this study suggest that in subjects with
Type 2 diabetes without cardiovascular disease, an elevated exercise SBP
is not associated with reduced exercise capacity and its modulation is
probably not related to glycemic control.
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BLOOD PRESSURE AND EXERCISE CAPACITY IN TYPE 2 DIABETES
Table 1. Baseline characteristics of the groups according to
median peak systolic blood pressure
n
Age, yr
Height, cm
Weight, kg
BMI, kg/m2
FBG, mmol/l
HbA1c, %
Resting HR, beats/min
Resting SBP, mmHg
Resting DPB, mmHg
Duration of diabetes, mo,
(range)
Therapeutic regimen n
Diet only
Oral hypoglycemic agents
⬍210 mmHg
⬎210 mmHg
P Value
14
56 (8)
172 (4)
93 (14)
31 (5)
6.8 (1.5)
6.5 (1.1)
74 (12)
130 (11)
84 (9)
14
50 (10)
173 (8)
92 (13)
31 (4)
7.1 (1.6)
6.5 (1.2)
80 (11)
139 (14)
86 (6)
0.08
0.84
0.76
0.66
0.62
0.82
0.24
0.06
0.49
26 (35) (0–113)
17 (25) (0–74)
11
3
8
6
0.5
0.42
pedaling rate of 50 –70 rpm. Expired air was continuously collected
for the determination of V̇O2, carbon dioxide production (V̇CO2),
pulmonary ventilation (V̇E), and the respiratory exchange ratio (RER)
(V̇CO2/V̇O2) on a breath-by-breath basis (Medgraphics, CPX Ultima,
St. Paul, MN). Heart rate (HR) was obtained using electrocardiographic monitoring during the test. Subjects exercised until volitional
exhaustion. Peak exercise (V̇O2 peak) was defined as the mean V̇O2
recorded in the last 15 s of the incremental exercise protocol concurrent with a RER ⱖ1.15. The exercise protocol was always performed
in the fasting state at the same time of the day at 20°C room
temperature.
BP. After 15 min of quiet rest in a supine position, resting BP was
then measured with the subject seated using an automated sphygmomanometer with headphone-circuit option (model 412, Quinton Instrument, Bothell, WA). BP during exercise was measured every 2
min throughout the maximal exercise protocol using the same automated sphygmomanometer as for the evaluation of resting BP. The
subjects were divided into two groups according to the median value
of peak SBP measured in each subject.
Statistical Analysis
A Student’s unpaired t-test and a one-way analysis of covariance
were used to evaluate the peak exercise parameters differences between the groups. The Mann-Whitney test was used for data not
normally distributed. The hypoglycemic regimen in the two groups
were compared using the Fisher’s exact test. The Pearson’s correlation
was used to assess associations between variables. All data are
presented as means (SD) unless otherwise specified. A value of P ⬍
0.05 was considered statistically significant.
RESULTS
Baseline characteristics of each group separated on the basis
of the median peak exercise SBP are presented in Table 1.
There was no statistical difference in all baseline characteristics between groups. Also, there was no statistical difference in
the proportions of subjects on hypoglycemic agents. However,
the subjects in the high-peak SBP group tended to be younger
[50 (SD 10) vs. 56 (SD 8) yr; P ⫽ 0.08], whereas a trend for
a lower resting SBP was observed in the low-peak SBP group
(⬍210 mmHg) compared with the high-peak SBP group
J Appl Physiol • VOL
DISCUSSION
These results suggest that, in subjects with Type 2 diabetes
without cardiovascular disease, an elevated exercise SBP is not
associated with reduced exercise capacity. Furthermore, SBP
modulation during exercise is not related to glycemic control in
our sample. To our knowledge, the present study is the first to
evaluate the impact of diverse exercise SBP responses on
parameters related to exercise capacity in subjects with Type 2
diabetes.
The presence of an elevated SBP response during exercise
may be a predictor of future hypertension (17, 18, 26). In
Table 2. Exercise capacity parameters observed in the
groups according to median peak systolic blood pressure
Total work, W
Exercise duration, s
V̇O2 peak,
ml䡠kg⫺1䡠min⫺1
V̇O2 peak, l/min
Peak HR, beats/min
⌬ HR, beats/min
V̇Emax, l/min
RER
Peak exercise SBP,
mmHg
⌬ SBP, mmHg
Peak exercise DPB,
mmHg
⌬ DBP, mmHg
Peak RPP,
mmHg䡠beats⫺1䡠min⫺1
Peak RR, breaths/min
⬍210 mmHg
⬎210 mmHg
P Value
169 (34)
725 (122)
202 (32)
823 (131)
0.01
0.09
27.0 (5.4)
2.47 (0.39)
160 (20)
85 (22)
103 (26)
1.20 (0.08)
31.0 (3.6)
2.84 (0.55)
169 (15)
89 (20)
120 (26)
1.16 (0.07)
0.03
0.046
0.18
0.64
0.09
0.24
193 (16)
63 (21)
235 (19)
96 (17)
⬍0.001
⬍0.001
94 (11)
11 (13)
97 (17)
11 (17)
0.60
0.88
30,822 (4,406)
42 (7)
39,676 (5,515)
43 (7)
⬍0.001
0.71
Values are means (SD). V̇O2 peak, peak oxygen consumption; V̇Emax, maximal pulmonary ventilation; RER, respiratory exchange ratio; RPP, rate pressure product; RR, respiratory rate; ⌬, Change (peak-resting).
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Values are means (SD); n, no. of subjects. BMI, body mass index; FBG,
fasting blood glucose; HbA1c: glycated hemoglobin; HR, heart rate; SBP,
systolic blood pressure; DPB, diastolic blood pressure. HbA1c normal range:
4.3– 6.2%.
(⬎210 mmHg) [130 (SD 11) vs. 139 (SD 14) mmHg; P ⫽
0.06].
Table 2 presents results from the peak exercise capacity
evaluation (V̇O2 peak). Per study design, there was a difference
between the peak SBP between groups (P ⬍ 0.001). A reduced
increment in SBP (peak SBP minus resting SBP) during
exercise was observed in the low-peak SBP group compared
with the high-peak SBP group [63 (SD 21) vs. 98 (SD 17)
mmHg; P ⬍ 0.001]. We observed a 13% reduction in the
relative and absolute V̇O2 peak and a 16% reduction in the peak
work rate in the low- compared with the high-peak SBP (all
P ⬍ 0.05). An elevated rate-pressure product (SBP ⫻ HR) was
also observed in subjects with higher peak SBP (P ⬍ 0.001).
After adjusting for age, relative V̇O2 peak was still significantly
higher in subjects with higher peak SBP (P ⬍ 0.05).
Significant relationships were observed between the resting
SBP (r ⫽ 0.422), absolute V̇O2 peak (r ⫽ 0.405), exercise
duration (r ⫽ 0.414), peak work rate (r ⫽ 0.454), and peak
exercise SBP (all P ⬍ 0.05) (Fig. 1). Whereas there was a
significant inverse relation between age and absolute values of
V̇O2 peak (r ⫽ ⫺0.612; P ⬍ 0.001) and a trend between age and
relative values of V̇O2 peak (r ⫽ ⫺0.332; P ⫽ 0.08), there was
no significant relation between age and peak SBP. No difference in the glycemic control (FBG and HbA1c) was observed
between the two groups.
BLOOD PRESSURE AND EXERCISE CAPACITY IN TYPE 2 DIABETES
895
Fig. 1. A: relationship between peak oxygen uptake (V̇O2 peak) and peak
exercise systolic blood pressure (SBP) B: relationship between exercise duration and peak exercise SBP. C: relationship between total work rate and peak
exercise SBP.
contrast, an elevated SBP response to exercise has been also
observed in endurance- and strength-trained athletes as well as
in subjects with prehypertension, and it seems to be positively
associated with exercise capacity (7, 25). In the present study,
important parameters related to exercise capacity, namely abJ Appl Physiol • VOL
Fig. 2. Schematic representation of the parameters influencing exercise capacity in patients with higher peak exercise SBP.
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solute V̇O2 peak, exercise duration, and peak work rate, were
positively related to peak exercise SBP. In addition, subjects
with an elevated SBP (⬎210 mmHg) in response to peak
exercise presented higher V̇O2 peak compared with subjects with
lower SBP (⬍210 mmHg) even after adjustment for age. The
literature regarding the BP response to exercise in subjects with
diabetes is sparse. A greater diastolic BP (DBP) in response to
submaximal exercise has been reported in Type 2 diabetes (2)
while an exaggerated SBP has also been documented in normoalbuminuric Type 1 (3) as well as in Type 2 diabetic
patients (13).
Type 2 diabetes is related to reduced LV systolic volume,
altered myocardial and diastolic functions and increased arterial stiffness (6, 11, 22). These are all important parameters
related to BP regulation, and they are potential contributors to
the reduced exercise capacity documented in diabetic individuals. The elevated peak exercise SBP observed in our subjects
is probably partly associated with the arterial stiffness observed
in subjects with diabetes (4, 6). In theory, a cascade of events
will take place after the appearance of arterial stiffness: 1)
increased afterload, 2) reduced stroke volume, 3) LV remodeling, 4) increased SBP, 5) diastolic dysfunction, 6) reduced
exercise performance, and 7) systolic dysfunction (6, 8). So,
how can we reconcile the positive results related to elevated
peak SBP observed in our subjects with the reported harmful
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BLOOD PRESSURE AND EXERCISE CAPACITY IN TYPE 2 DIABETES
J Appl Physiol • VOL
ence in terms of resting or peak exercise HR, it seems unlikely
that sympathetic overactivity might have accounted for our
results. However, we cannot exclude the possibility that a
subtle change in sympathovagal activity, i.e., sympathetic
predominance, might have influenced our findings (22). Finally, we cannot ignore that these differences might be related
to whether the maximal effort was attained or not because we
used V̇O2 peak instead of V̇O2 max. However, this is unlikely
because our two groups reached similar RER both above 1.15,
and it was recently shown that V̇O2 peak is likely to be a valid
index of V̇O2 max (5).
Further research is needed to evaluate whether 1) these
results represent an increase or a preservation of exercise
performance, 2) LV remodeling is related to increased peak
SBP and exercise capacity in these subjects, and 3) these
results will be influenced in subjects with LV diastolic function.
In conclusion, our results suggest that, in subjects with Type
2 diabetes without cardiovascular disease, an elevated exercise
SBP is not associated with reduced exercise capacity and that
its modulation is probably not related to glycemic control.
GRANTS
This work was supported in part by the Canadian Diabetes Association and
the Quebec Heart Institute Foundation. P Brassard is the recipient of a graduate
research scholarship in pharmacy (PhD) from the Rx & D Health Research
Foundation Awards Program funded in partnership with the Canadian Institutes of Health Research (CIHR). A. Ferland is supported by the CIHR. P.
Poirier is a clinician-scientist of the Fonds de la Recherche en Santé du
Québec.
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The principal limitation of the present study is the absence of
a control group of nondiabetic subjects. Consequently, we used
the terms elevated and high SBP instead of exaggerated SBP
because we did not compare our results with a “normal”
exercise response obtained from a control group. Nevertheless,
the goal of this study was to investigate the impact of an
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Type 2 diabetes. Therefore, the group with peak exercise SBP
below 210 mmHg could be considered as control subjects
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