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1 Section of Vascular Medicine, Divisions of 2 Internal Medicine, 3 Cardiology, 4 Endocrinology and 6 Geriatrics, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262; and 5 Division of Pulmonary Medicine, University of Oregon Health Sciences Center, Portland, Oregon 97201
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Persons with type II diabetes mellitus
(DM), even without cardiovascular complications have a decreased
maximal oxygen consumption (
O2 max) and
submaximal oxygen consumption
(O2) during
graded exercise compared with healthy controls. We
evaluated the hypothesis that change in the rate of
O2 in response to the onset
of constant-load exercise (measured by
O2-uptake
kinetics) was slowed in persons with type II DM. Ten premenopausal
women with uncomplicated type II DM, 10 overweight, nondiabetic
women, and 10 lean, nondiabetic women had a
O2 max test. On two
separate occasions, subjects performed 7-min bouts of constant-load
bicycle exercise at workloads below and above the lactate threshold to
enable measurements of O2
kinetics and heart rate kinetics (measuring rate of heart rate rise).
O2 max
was reduced in subjects with type II DM compared with both lean and
overweight controls (P < 0.05).
Subjects with type II DM had slower
O2 and heart rate kinetics
than did controls at constant workloads below the lactate threshold.
The data suggest a notable abnormality in the cardiopulmonary response
at the onset of exercise in people with type II DM. The findings may
reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.
oxygen consumption; exercise test; female
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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IT HAS PREVIOUSLY BEEN OBSERVED that persons with type
II diabetes mellitus (DM), even in the absence of clinical
cardiovascular disease, have a reduced maximal oxygen consumption
(O2 max) compared with
nondiabetic persons (20). In addition, the rate of
increase in oxygen consumption
(O2) during graded treadmill exercise is attenuated in persons with type II DM compared with nondiabetic individuals (20). These data suggest that the reduced O2 max in type II DM
may not simply be due to the early termination of graded exercise, or
deconditioning, but to a qualitative difference in the rate of rise in
O2 with graded exercise.
However, observations made during incremental exercise do not represent
steady-state phenomena and may be influenced by a variety of factors,
including the rate of progression in workload and the ability of the
cardiovascular system to respond to the increased work demand. To
control for these variables, constant-load, steady-state exercise can
be utilized. Under constant-load conditions,
O2 at steady state is in
direct proportion to the external work demand. However, during the
transition from rest to constant-load exercise, the rate of rise of
O2 reflects the dynamic
response of the cardiovascular system and skeletal muscle oxygen
uptake. A rapid increase of
O2 to steady state is seen in
healthy, physically trained individuals (3, 31). In contrast, a delayed
rise in O2 to steady state is observed in patients with decreased cardiac function or in chronic obstructive pulmonary disease (5, 25, 26).
To evaluate the effects of type II DM on
O2 kinetics, we had 10 sedentary women with uncomplicated type II DM perform bouts of
constant-load exercise. In addition, we measured heart rate kinetics,
which evaluate the rate of rise in heart rate at the beginning of
exercise. The effects of obesity (commonly observed in type II DM) were
controlled for by including two control groups (both sedentary). One
group was moderately overweight, similar to the group with type II DM,
and one group was composed of lean women.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Subjects
Ten moderately overweight, sedentary, premenopausal women with type II DM and no complications or comorbid conditions, 10 moderately overweight but otherwise healthy women of similar age and activity levels, and 10 healthy lean women of similar age and physical activity levels were studied. Only women were enrolled because preliminary data suggested that exercise performance may be more affected by type II DM in women than in men (unpublished observations). No subject was >140% of ideal body weight. All women displayed sedentary behavior defined as not participating in a regular exercise program (>1 bout of exercise per week). Furthermore, use of a low-level physical activity recall (LOPAR) questionnaire ensured that physical activity levels were similar among subjects (20, 21). Presence of type II DM was documented by chart review, which confirmed the diagnosis as well as the presence of drug treatment for diabetes. Persons with type II DM were included in the study if their diabetes was treated by diet or oral agents, but not by insulin, because subjects treated with insulin tend to have more advanced disease. Two patients with type II DM were treated with diet only, six with glyburide, and two with glipizide. Duration of diabetes (from diagnosis) was noted. Other than oral agents, subjects with type II DM were taking no other medicines. Women with type II DM were accepted for study only if they had glycosylated hemoglobin levels (Hb AIc) levels <9% (adequate control) on therapy.Women who were current smokers were not accepted for study because smoking can impair cardiovascular exercise performance. Former smokers must have been abstinent for the past 2 yr.
Premenopausal women between the ages of 30 and 50 yr were included in the study. Premenopausal status was evaluated in all women by history of regular menstrual cycles and by measurements of serum follicle-stimulating hormone (FSH) levels. For the purpose of uniformity and to rule out effects of widely differing levels of female hormones on exercise as well as to minimize potential effects of progesterone on ventilation, women were tested in the midfollicular phase (days 6-10) of the menstrual cycle (14, 22).
Absence of comorbid conditions was confirmed by history, physical examination, and laboratory testing. Distal symmetrical neuropathy was evaluated by symptoms (numbness, paresthesia) and signs. Persons who had clinically evident distal symmetrical neuropathy were excluded from further study because of possible effects on exercise performance (10). Three subjects were excluded by using these criteria.
Through the use of resting echocardiographic criteria, persons were
excluded who had the presence of global or regional contractile abnormalities (12). Exclusions occurred if
1) regional wall motion
abnormalities suggested coronary disease,
2) left ventricular (LV) wall
thickness was >1.3 cm (suggesting moderate LV hypertrophy), or
3) there was decreased
contractility, i.e., fractional shortening <35%. Subjects were also
excluded if they had evidence of ischemic heart disease by history or
abnormal resting or exercise electrocardiogram (ECG) (
1-mm flat or
downsloping S-T segment depression). Persons with angina or any other
cardiac or pulmonary symptoms potentially limiting exercise performance
were excluded as well. Presence of systolic blood pressure >130 mmHg
at rest or >190 mmHg with exercise or diastolic pressure >90 mmHg
at rest or >100 mmHg with exercise was also grounds for exclusion.
Persons with autonomic insufficiency, assessed by measuring variation
in R-R intervals with cycled breathing and by the presence of a
>20-mm fall in upright blood pressure without a change in heart rate,
were excluded because of possible effects on exercise performance (9).
Subjects with proteinuria (urine protein >200 mg/dl) or a creatinine
2.0 mg/dl, suggestive of renal disease, were excluded. Renal disease was grounds for exclusion because it can alter exercise performance (2).
Control subjects were screened identically to persons with type II DM. These subjects were taking no medications, had a normal Hb AIc, and had no history of any active medical problems.
Design (Study Protocol)
Subjects were evaluated over the course of six visits on separate days. Subjects made an initial visit to the General Clinical Research Center (GCRC) to have a history and physical examination, blood draws, and questionnaire administrations. A resting ECG was obtained, and a familiarization bicycle test was performed. During the two subsequent visits, a diet interview was administered and underwater weighing was performed. Three days before the fourth visit (to control for the effects of diet on exercise performance), subjects began receiving all meals from the GCRC. On the fourth visit, subjects performed a graded maximal bicycle exercise test to determine the lactate threshold andO2 max. On the fifth and sixth visits, four 7-min bouts of constant-load exercise were performed each day (with 15-min rest periods between bouts) so that
three bouts at 20 W, three bouts at 30 W, and two bouts at 80 W were
performed in total over the 2-day period. Performance of multiple bouts
enabled averaging of O2
kinetic data within a workload to reduce variability of results.
Graded Maximal Exercise Test
After subjects fasted overnight,O2 max and lactate
threshold were determined during a graded bicycle protocol to
exhaustion. Each test began with the subject seated at rest on the
cycle ergometer (Cardio-2, Medical Graphics, Minneapolis, MN) breathing
into a mouthpiece connected to a metabolic cart (CPX-D, Medical
Graphics). All testing was done with the subject in the upright seated
position. Three minutes of resting data were collected to obtain
baseline measurements before exercise. The rest period was prolonged at the discretion of the investigator if additional time was required for
adjustment to the mouthpiece and stabilization of physiological variables. To obviate the need to overcome inertia of the ergometer flywheel at the start of exercise, the flywheel was driven at 60 rpm
during rest by an electric motor, which was turned off synchronous with
the start of exercise. At the start of exercise, the work rate was
increased in 10 W/min increments, and the incremental portion of the
test was 12-15 min in duration.
O2 max was defined as
O2 remaining unchanged or
increasing <1
ml · kg
1 · min1
for 30 s or more despite an increment in workload (29).
O2 and carbon dioxide
production (CO2)
were measured, breath by breath, at rest and during
exercise. Peak O2 data were averaged over 30-s intervals. Arm blood pressure (by auscultation) and
heart rate (by 12-lead ECG) were obtained every minute during exercise.
Cardiac status was monitored throughout the test by 12-lead ECG. The
respiratory exchange ratio was calculated as CO2/O2.
O2 was normalized on a per
kilogram basis and per lean body mass as well as presented as
milliliters per minute. Normalization by lean body mass was done to
avoid confounding, which could result from differences in the fat mass
between lean and overweight (type II DM and overweight control)
subjects.
The slope of the increase in
O2 per increase in work
rate
(
O2/work
rate) was analyzed by least squares linear regression excluding the
first 2 min and last minute of graded exercise data as previously
described (11).
Blood was drawn every minute during the first
O2 max test to enable
determination of the lactate threshold. The lactate threshold was defined as the point at which a net increase in venous
lactate accumulation was observed during incremental maximal exercise.
Venous lactate (mmol) vs.
O2 was plotted for
determination of the lactate threshold for each patient. The
O2 at the lactate threshold
was determined and recorded from each plot. Confirmation of the lactate
threshold was performed by using ventilatory data and the V-slope
technique. CO2
was plotted against O2, and the ventilatory threshold was labeled where the slope of
CO2 vs.
O2 exceeded 1.0. In all
cases, V-slope analyses confirmed lactate threshold measurements.
Constant-Load Exercise Tests
An overnight fast preceded each test day. Each test began with 3 min of resting baseline measurements as described in Graded Maximal Exercise Test. After this period, with the flywheel driven by the motor as described Graded Maximal Exercise Test, the preselected workload (20, 30, or 80 W) was then imposed and the subject maintained pedaling at 60 rpm for 7 min. This protocol allowed all subjects to reach steady-stateO2 at 20 and 30 W but not
at 80 W, which was above the lactate threshold.
Kinetic Measurements During Constant-Load Exercise
O2 kinetic
measurements.
Three phases to the response of
O2 from rest to
moderate constant-load exercise were proposed by Whipp and Mahler (30). At the onset of exercise,
O2 from the lungs normally
increases abruptly for the first 15 s (phase
I) as pulmonary blood flow increases. Next, the
O2 increases exponentially
in phase II with a time constant (
) of ~30-45 s representing
further increases in blood flow and decreased venous
O2 content. Phase
II ends as gas exchange approaches a steady state.
Phase III is steady-state O2 below the lactate
threshold, but above the lactate threshold; phase
III O2
kinetic responses are not steady-state (phase
III drift), and modeling is altered accordingly (30).
O2 was measured breath by
breath. After collection, the
O2 data were
transferred to an ASCII file and filtered, and then a
O2 value was assigned to
each second by extrapolation between breaths by using a program
developed and validated at our laboratory. To dampen noise and enhance
resolution of data, the data from repetitions within a workload were
temporally aligned to a time at the start of exercise and superimposed
to yield a single second-by-second averaged record of the tests for
each subject at a given workload. The and the actual change in
O2 from rest to
steady-state O2
were then calculated by using a statistical program as previously described (6). With use of this program, a single exponential curve was
fit to the data from the onset of exercise to the end of the sixth
minute of steady-state exercise in 20- and 30-W transitions. Because we
expected that 80 W would constitute high-intensity exercise (i.e.,
above the lactate threshold) in the majority of patients (given the
sedentary profile of the patients), we modified the modeling procedures
for this workload to enable comparability between those for whom 80 W
was above the lactate threshold and those still below the lactate
threshold at 80 W. Thus, to minimize the impact of a
phase III drift in
O2 (non-steady-state
O2 associated with
constant-load exercise O2
above the lactate threshold), 80-W transitions were analyzed by using a
single exponential curve fit from the onset of exercise to the end of
the third minute of exercise.
Heart rate kinetic measurements. Heart rate was monitored beat by beat from the R-R interval of the ECG signal (Quinton Q-plex). These data underwent analog-to-digital conversion and were subjected to kinetic analyses as described in Kinetic Measurements During Constant-Load Exercise.
Specific Methods
Echocardiographic measurements. Two-dimensional and Doppler echocardiography were performed by using standard methods (12) to exclude the presence of significant valvular pathology, LV global dysfunction and segmental wall motion abnormalities (Sonos 2500, Hewlett-Packard, Andover, MA). Chamber sizes, LV end-systolic and diastolic chamber dimensions and wall thickness, fractional shortening, and the area-length method for measurement of cardiac volume (to measure ejection fraction) were quantitated by standard techniques for all individuals. All readings were done by one of the authors (E. E. Wolfel), a cardiologist who is skilled in these readings and who was blinded to the diagnostic status of the patient. Measurements of diastolic filling were assessed by analyzing mitral valve and pulmonary venous flow patterns by using Doppler techniques.
Dietary control. Three days before the fourth visit, subjects began diet regulation. The diet was administered until the sixth visit was completed. With the use of a diet interview administered during the third visit, subjects were given a diet composed of the percentage of each macronutrient that they customarily ate for all meals. Customary macronutrient pattern was used because a change in diet may affect the respiratory exchange ratio. Overnight fasting (from 10:00 PM the preceding night) was observed before the underwater weighing test day and each exercise test day.
Body composition and hydrodensitometry. Body composition and hydrodensitometry measurements were performed according to standard methods and were used to derive fat-free mass. Percent body fat was estimated from body density by using the revised equation of Brozek et al. (4). Body fat distribution was determined by using the waist-to-hip ratio, where the waist circumference was measured at one-half the distance from the xiphoid process to the navel and the hip circumference was measured at the level of the greater trochanter.
Tests of autonomic insufficiency. To evaluate autonomic insufficiency, we measured variation in R-R intervals with cycled breathing (7, 9). The method for obtaining R-R variability was as follows. The patient, while resting supine, breathed five times per minute, coordinating breaths with a visual electronic signal. This was repeated for 5 min. To obtain data, maximum inspiratory heart rate was subtracted from the minimum expiratory heart rate. Variations of >30 beats/min were considered normal, and values <20 beats/min were considered abnormal (7, 9). In addition, autonomic insufficiency was evaluated by measuring, in lying and standing subjects, heart rates and blood pressures (>20-mm fall in upright systolic blood pressure without a change in heart rate). Subjects who failed to meet these criteria were excluded from study. Three potential subjects were excluded in this way.
Blood collection and preparation. Blood was drawn at baseline for the measurement of glucose, insulin, and plasma FSH levels and of Hb AIc. Blood lactate concentrations were measured every minute during the graded exercise test to determine the lactate threshold in all subjects. In addition, lactate was measured at rest and at peak exercise during the constant-load tests. For the measurement of blood lactate concentration, a 20-gauge intravenous catheter was placed in a forearm vein, with a three-way stopcock to facilitate blood drawing, and patency was maintained with heparinized saline. For each sample, 50 µl of blood were withdrawn and immediately deproteinized in 3% perchloric acid and stored at room temperature.
Assay methods. Lactate concentration was assayed by a lactate dehydrogenase method (23). The lactate threshold was determined as the point at which blood lactate concentration began to progressively increase in the blood. Hb AIc was measured by glyc-affin GHB columns (Isolab). Serum insulin concentrations were measured by radioimmunoassay (18, 32). Serum glucose concentrations were measured by the glucose oxidase method (17). Plasma FSH levels were measured by a chemiluminescence assay (19).
LOPAR questionnaire.
This questionnaire has been modified for use in persons with type II DM
and peripheral arterial disease as well as in sedentary controls (20,
21). The subjects were asked a series of questions to itemize their
time (reporting specific activities) into work, leisure, and housework
categories for the previous week. Questionnaire results were expressed
in metabolic equivalents (METs) where 1 MET equals resting
O2 (3.5 ml · kg1 · min1).
Scores are reported in MET hours per week, derived by multiplying the
amount of time spent performing an activity by the MET value of the
activity. This questionnaire was primarily used in the present study to
quantify the activity level of all participants.
Data analysis. The three groups were compared by using a between-subjects ANOVA. The Student-Newman-Keuls test was used for post hoc analysis. Where data were nonparametric, the Kruskal-Wallis test was used to make between-group comparisons. Correlations were done by using Pearson's product-moment correlation.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Demographic Data
Ten subjects were enrolled in each group (Table 1). There were no significant differences among the three groups in age. The subjects with type II DM had been diagnosed with the disease an average of 3 yr. The group with type II DM and the overweight control group were not different with regard to weight, body mass index, or fat-free mass. However, these two groups differed from the lean control group in terms of the above measurements (Table 1). Fasting insulin, fasting glucose, and Hb AIc levels did not differ between the lean and overweight control groups. However, the group with type II DM had higher insulin, glucose, and Hb AIc levels than did the other two groups (all P < 0.05). Analysis of the physical activity recall revealed that there was no significant difference among the three groups in terms of habitual physical activity level measured by LOPAR. (Table 1).
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Graded Maximal Exercise Test
O2 max was lower in the
group with type II DM than in the other two groups whether expressed in
milliliters per minute or normalized to kilograms or kilograms of
fat-free mass (Table 2). In addition, the
maximal respiratory exchange ratio did not differ among
groups and suggested a maximal effort in all three groups (all values
were over 1.10). Maximal heart rate also was not different among
groups.
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To evaluate the
O2/work rate
relationship, we compared the slopes of the
O2/work rate
measured during the graded test between the three groups (Fig.
1). Overweight and lean groups exhibited
nearly identical slopes (Fig. 1). Data from the overweight group were
shifted upward, reflecting the effect of obesity on the absolute
O2/work rate. In
contrast, data from the group with type II DM, which similarly shifted
upward, revealed a decreased slope (P < 0.05).
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Kinetic Responses to Constant-Load Exercise
O2 kinetics were slower in
persons with type II DM than in the lean and overweight control groups
at the 20- and 30-W workloads (both P < 0.05, comparison between persons with type II DM and the other two
groups) and tended to be slower at 80 W as well (P = 0.09; Figs.
2 and 3, Table
3). The heart rate kinetics were slower in
persons with type II DM than in the other two groups at all three
workloads (both P < 0.05, comparison
between persons with type II DM and the other 2 groups). The values of
the overweight and lean control groups were not different from each
other in terms of the O2 and
heart rate kinetic measurements.
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Steady-State Measurements During Constant-Load Exercise
Respiratory exchange ratios did not differ between groups during constant-load exercise workloads (Table 4). However, lactate concentrations were higher at 30 and 80 W (both P < 0.05) in the group with type II DM than in the other two groups. Lactate concentration was higher in the group with type II DM than in the lean group at 20 W and tended to be higher in persons with diabetes than in the overweight control group. Steady-stateO2 did
not differ between groups at any workload. However, steady-state
O2 as a percentage of
O2 max was higher for
the group with diabetes at all three constant-load workloads (Table 4).
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Correlations Between Maximal and Steady-State Values
There was an inverse correlation across the three groups between theO2 and
O2 max such that the
shorter the , the greater the
O2 max
(r = 
0.36,
r = 0.38, and
r = 0.38, all P < 0.05 for 20, 30, and 80 W,
respectively). There was also an inverse correlation between heart rate
kinetics and O2 max
such that the shorter the for heart rate kinetics, the greater the O2 max
(r = 0.59,
r = 0.45, and
r = 0.60, all
P < 0.05, for 20, 30, and 80 W,
respectively).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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In the present study, we found that women with type II DM had impaired
maximal and submaximal cardiopulmonary responses to exercise, even
though they had no evidence of clinical cardiovascular disease or
diabetic complications. We had previously observed a lower
O2 response to submaximal
workloads during submaximal graded exercise testing in persons with
type II DM compared with controls (20). We reasoned that this finding
might be due to slowed O2
kinetic responses in subjects with type II DM. In the present study,
constant-load testing was used to confirm that the
O2/workload relationship was
impaired and that
O2
kinetic responses were in fact slowed in type II DM. In
addition, the presence of slowed heart rate kinetics in the women with
type II DM suggested that a cardiac component may be partially
responsible for the abnormalities observed.
In the present study, to confirm our finding of slowed
O2 kinetics, we
used multiple constant workloads, with each workload repeated several times over 2 days. We documented the consistent finding of slowed kinetics in persons with type II DM at the two workloads below the lactate threshold. However, at the one workload above the lactate threshold, persons with type II DM only tended to
have slower kinetics than did controls. This may have been due in part
to limitations in monoexponential modeling techniques at this
workload.
Importantly, the presence of greater than ideal body weight could not
account for the lower
O2 max or slowed
O2 and heart rate
kinetic responses observed in the study because the overweight and lean
groups had similar responses. Overweight controls were not different in
terms of weight and fat-free mass from subjects with type II DM. In
addition, O2 max was
lower in persons with type II DM than in controls, whether presented in
milliliters per minute or milliliters per kilogram per minute.
Differences in habitual physical activity level could also not account
for the exercise differences observed between persons with type II DM
and control subjects. The use of the LOPAR questionnaire revealed that
physical activity levels did not significantly differ between groups.
The present study was performed in women only. The reason for studying
women was that we observed that women with type II DM had a lower
O2 max relative to
their nondiabetic counterparts than did men with type II DM compared
with nondiabetic men (unpublished observations). The reason for
studying premenopausal women only was for greater homogeneity of the
sample in terms of age. The finding of cardiopulmonary exercise
abnormalities during maximal and submaximal exercise was especially
interesting given that the women studied had only had the clinical
diagnosis of diabetes for a relatively short time.
Whereas, in healthy individuals,
O2 kinetic measurements are
thought to closely reflect the time course of changing
O2 of exercising muscles,
persons with specific cardiovascular or cardiopulmonary diseases have
rate-limiting defects in the oxygen delivery and utilization process
(5, 25, 26, 31). In the healthy individual, where oxygen delivery is
not rate limiting during submaximal exercise,
O2 kinetics
reflect the oxidative resynthesis rate of phosphocreatine (i.e.,
primarily reflect muscle bioenergetics and oxygen diffusion at the
tissue level) (31) and therefore the utilization
aspects of O2 during
exercise. However, in disease states in which oxygen delivery is
compromised, for example, by a limited cardiac output response,
O2 kinetics also reflect the
ability of the cardiovascular system to deliver oxygen to working
muscle and therefore may reflect impaired oxygen delivery (28).
Consistent with this thinking is the finding that the of
phase II of
O2 kinetics (rise to steady
state) is prolonged in patient groups with abnormal cardiovascular
responses to exercise, such as pulmonary vascular disease and cyanotic
congenital heart disease (25, 26). Further evidence for a relationship between impaired oxygen delivery and slowed kinetics is the observation that patients with pulmonary vascular disease who underwent surgical procedures that improved pulmonary hemodynamics had faster
O2 kinetics after the
procedure (25).
There is evidence to support the idea that both central (cardiac) and peripheral factors may be related to the exercise abnormalities associated with type II DM. Studies have not thoroughly assessed the ability of the person with diabetes to utilize oxygen during exercise. Allenberg et al. (1) and Lithell et al. (16) reported that citrate synthase activity in skeletal muscle increased markedly after exercise training in type II DM, thereby showing the normal response. In contrast, Simoneau and Kelley (27) recently reported a higher than normal ratio between glycolytic and oxidative enzyme activities that was explained not only by an increased activity for glycolytic enzymes but also by decreased maximum velocities for citrate synthase and cytochrome-c oxidase enzymes in the subjects with type II DM compared with lean and nondiabetic obese subjects. Another recent study investigated whether older persons with impaired glucose tolerance or type II DM had an increased frequency of mitochondrial DNA deletions in skeletal muscle compared with an age-matched nondiabetic control group (15). The authors found that one particular deletion (4,977 bp) as well as other deletions were significantly increased in the muscle tissue of subjects with type II DM or impaired glucose tolerance compared with nondiabetic individuals. Future studies should further explore the effects of type II DM on skeletal muscle metabolism.
There is also evidence suggesting that impaired myocardial function (and subsequently oxygen delivery) in persons with type II DM may play a critical role in the abnormal exercise performance observed in persons with type II DM compared with controls (13, 24). In the present study, the finding of slowed heart rate kinetics supports the likelihood of a cardiac factor as a component of the exercise abnormalities observed. In other studies, a reduced cardiac output during exercise has been reported in persons with type II DM vs. controls (13, 24). One study used right heart catheterization to show the presence of a reduced cardiac output in men with diabetes during submaximal workloads of supine bicycling exercise (13). Another study, which used noninvasive methods (24), also measured cardiac output during exercise in persons with diabetes and reported similar results. Methodological issues limit interpretation in both studies. For instance, subjects were included who were taking insulin and oral agents. Persons with both type II DM and type I DM were studied, although evidence suggests that these groups may show differing hemodynamic responses to exercise (8). Also, subjects were not separated according to physical activity levels or carefully matched for age, factors which can strongly affect exercise performance. Finally, the presence of autonomic dysfunction was not evaluated in the first study. However, the suggestion from the literature is that some degree of LV dysfunction may occur in persons with diabetes.
To summarize, the results of the present study demonstrate that
premenopausal women with uncomplicated diabetes have impaired O2 responses to maximal and
submaximal exercise. Further studies will be necessary to evaluate
whether cardiac output, arteriovenous oxygen difference, and/or
aspects of skeletal muscle metabolism are involved in causing the
abnormalities observed. Understanding the magnitude and causes of the
exercise impairments observed in this relatively healthy group of women
with type II DM is important to potentially target appropriate
interventions to improve exercise performance and thereby perhaps
prevent increasing disability.
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ACKNOWLEDGEMENTS |
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The authors thank Sheri Kozemchak and the other nurses of the General Clinical Research Center for their excellent work on this study. In addition, the authors thank the participants in the study, who gave generously of their time and effort. The authors thank Vermont Medical, Inc., for their support of our research.
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FOOTNOTES |
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This study was funded by a clinical research grant from the American Diabetes Association to J. G. Regensteiner and by the General Clinical Research Center RR 501RR-00051. W. R. Hiatt is the recipient of the National Institutes of Health Academic Award in Vascular Disease.
The study was presented in abstract form to the American Federation for Clinical Research in Washington, DC, in May 1997.
Address for reprint requests: J. G. Regensteiner, Sect. of Vascular Medicine, Divs. of Internal Medicine and Cardiology, Univ. of Colorado Health Sciences Center, Box B-180, 4200 E. Ninth Ave., Denver, CO 80262 (E-mail: judy.regensteiner{at}uchsc.edu).
Received 9 December 1997; accepted in final form 10 March 1998.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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