Annals of African Medicine

ORIGINAL ARTICLE
Year
: 2012  |  Volume : 11  |  Issue : 2  |  Page : 96--102

Gender differences in the variables of exercise treadmill test in type 2 diabetes mellitus


Ajayi E Adekunle1, Anthony O Akintomide2,  
1 Department of Internal Medicine, University Teaching Hospital, Ado Ekiti, Nigeria
2 Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria

Correspondence Address:
Ajayi E Adekunle
Department of Internal Medicine, University Teaching Hospital, Ado Ekiti
Nigeria

Abstract

Background: Exercise capacity, like some other variables of exercise stress test, is a strong predictor of cardiovascular and overall mortality. Many confounding factors, including gender, have been found to affect exercise capacity. This study evaluated whether exercise capacity differs in age-matched type 2 diabetic Nigerian men and their women counterparts and the hemodynamic variables of exercise treadmill test that correlate with exercise capacity in them. Materials and Methods: A total of 61 type 2 diabetics (male = 34; female = 27) aged 30 to 60 years who were recruited through the Medical Out-patient Department of OAUTHC, Ile Ife, Nigeria, underwent symptom-limited maximal treadmill exercise using Bruce protocol. Result: Patients had comparable clinical and demographic patterns. There was no gender difference in the chronotropic response to exercise. Males had faster heart rate recovery (HRR) than females. Though both sexes had similar resting systolic blood pressure (SBP), males had significantly higher peak SBP than females (216.2 ± 23.7 mmHg vs 203.3 ± 21.7 mmHg; P = 0.03). Exercise capacity was significantly higher in males (7.5 ± 2.0 METs) than females (6.4 ± 1.5 METs); P = 0.01. Significant correlates of exercise capacity in both sexes were fasting plasma glucose, resting diastolic blood pressure, Duke Treadmill Score, and HRR. Majority of the patients were in moderate DUKE risk subgroup and there was no statistically significant difference between males and females in this regard. Conclusion: Gender difference occurs in the exercise capacity of diabetic patients and the factors associated with this disparity may be related to gender differences in resting heart rate and HRR, both reflecting a withdrawal of vagal tone.



How to cite this article:
Adekunle AE, Akintomide AO. Gender differences in the variables of exercise treadmill test in type 2 diabetes mellitus.Ann Afr Med 2012;11:96-102


How to cite this URL:
Adekunle AE, Akintomide AO. Gender differences in the variables of exercise treadmill test in type 2 diabetes mellitus. Ann Afr Med [serial online] 2012 [cited 2021 Jan 21 ];11:96-102
Available from: https://www.annalsafrmed.org/text.asp?2012/11/2/96/93532


Full Text

 Introduction



Clinical and observational studies have shown that exercise capacity is a strong predictor of cardiovascular and overall mortality. [1] This is also true of some of the variables of exercise such as heart rate recovery (HRR), [2],[3] chronotropic response, [4] and Duke Treadmill Score (DTS). [5] Despite this, there is widespread tendency to ignore exercise testing in clinical management of patients with diabetes mellitus even when evidence abound showing that exercise improves health status in patients with diabetes mellitus [6] and the need to properly evaluate the patients before prescribing such exercise. The prognostic and therapeutic benefits of exercise testing cannot be overemphasized. [6]

However, it is known that many factors, including female gender, are associated with a reduction in exercise capacity, as reflected by a decrease in maximal workload achieved or maximal oxygen consumption. [7] Though the differences in exercise capacity between men and women have largely been attributed to nonmodifiable differences in cardiac output and skeletal muscle mass, [7],[8] determining the most important parameters affecting exercise capacity in diabetic men and women is difficult because of the numerous confounding factors such as age, body mass index, and glycemic control.

The purpose of this study was to determine whether exercise capacity differs in age-matched type 2 diabetic Nigerian men vs their women counterparts and the hemodynamic variables of exercise treadmill test that correlate with exercise capacity in them. To the best of our knowledge, relevant studies addressing this issue from Nigeria are scarce, if any.

 Material and Methods



A total of 61 type 2 diabetics (male = 34; female = 27) aged 30 to 60 years were recruited through the Medical Out-patient Department of Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Nigeria. Ethical clearance for the study was approved by the Ethics and Research Committee of the hospital in conformity with ethical guidelines of the 1975 Declaration of Helsinki and all the participants gave written consent to participate.

Demographic parameters of subjects were noted and recorded. All subjects were clinically examined to evaluate their body mass index (BMI) and cardiovascular status at rest. Subjects were considered diabetic if they had fasting plasma glucose (FBG) th > 126 mg/dl (7.0 mmol/l) [9] or if they were on hypoglycemic medication. FBG and 2-hour postprandial plasma glucose were obtained 24 hours prior to the procedures. Resting 12-lead electrocardiogram (ECG) was done to exclude patients with baseline ST-segment abnormalities and bundle branch block. Also excluded were patients with coexisting hypertension or who were on antihypertensive(s), established chronic kidney disease or serum creatinine >1.5 mg% (132 umol/l), congestive heart failure, valvular heart disease, and other diseases known to influence left ventricular (LV) function such as thyroid disease and severe obesity.

All the subjects underwent treadmill symptom-limited maximal exercise using Bruce protocol [10] with Schiller CS-200 machine. The protocol continued until one of several endpoints was reached. These included if the patient requested that the exercise be terminated; developed severe chest pain, fatigue, leg discomfort or dyspnea; developed frequent premature ventricular beats, developed a systolic blood pressure (SBP) >250 mmHg or a drop in the pretest SBP >10 mmHg; or developed any other reasons necessitating termination of exercise.

The following exercise variables (as defined) were recorded:



Peak systolic blood pressure (pSBP): Highest SBP during exercisePeak diastolic blood pressure (pDBP): Highest DBP during exerciseExercise capacity: estimated metabolic equivalent (MET) of workload which was calculated from the exercise time using the regression equation: MET = 1.11 + 0.016Y (exercise time in seconds). [11] Percentage of normal exercise capacity achieved: (Achieved exercise capacity/the predicted peak exercise capacity) x 100; where predicted peak exercise capacity is 18 - (0.15 x age). [12] Heart rate reserve: [(peak HR - HR at rest)/(220 - age - HR at rest)] x 100, with value ≤70% taken as low. [13] This is also a measure of chronotropic competence. [14] HRR: measured as the difference between maximal heart rate and 1-minute heart rate immediately after peak exercise. Abnormal HRR was defined as HRR ≤12 beats per minute. [3] Recovery time: Time between end of exercise and reversal of heart rate to pre-exercise rate.DTS: Exercise duration (minutes) - 5 x ST- segment deviation (millimeters) - 4 x treadmill angina index [15] with the Duke risk grouping, as shown in [Table 1].{Table 1}

Statistical Analysis

SPSS version 11.0 software (SPSS, Chicago, IL, USA) was used in the analysis of the data. Continuous variables were expressed as mean ± SD, while categorical variables were expressed as counts (percentages). Comparison between two groups was assessed by the Students t-test for independent variables, while the Chi-square analysis was used to compare proportions. Pearson's correlation was used to investigate the correlation of variable factors. P values <0.05 were considered statistically significant.

 Results



As shown in [Table 2], clinical and demographic patterns were comparable in both sexes, except the resting heart rate that was significantly higher in females than males.{Table 2}

There was no significant difference in the number of males who attained at least 85% of the age-predicted maximum heart rate compared with females. A trend similar to this observation was also seen in the percentage of heart rate reserve used by both sexes during exercise. On the whole, 23% of the study population did not achieve at least 85% of the age-predicted maximum heart rate, and their resting systolic and DBPs were observed to be significantly higher than those who achieved at least 85% of the age-predicted maximum heart rate (127.45 ± 17.43 mmHg vs 145.71 ± 17.47 mmHg; P = 0.001 and 79.68 ± 10.43 mmHg vs 90.86 ± 7.83 mmHg; P<0.001, respectively). HRR was significantly higher in males than females. [Table 3] shows that more males also had normal HRR than females.{Table 3}

Though both sexes had similar resting SBP, males had significantly higher pSBP than females (216.2 ± 23.7 mmHg vs 203.3 ± 21.7 mmHg; P = 0.03).

The mean exercise capacity for the study population was 7.02 ± 1.84. As shown in [Table 4], exercise capacity was significantly higher in males (7.5 ± 2.0 METs) than females (6.4 ± 1.5 METs); P = 0.01. Percentage of expected normal exercise capacity achieved in males was also significantly higher than in females (72.7 ± 19.9% vs 59.9 ± 13.3%; P = 0.01). Significant correlates of exercise capacity in both sexes are shown in [Table 5]. They were FBG, resting DBP, DTS, and HRR. Other gender-specific correlate was heart rate reserve (r = 0.80, P = 0.002) in males.{Table 4}{Table 5}

The reason for terminating exercise was fatigue in 95.1% and SBP greater than 250 mmHg in 4.9% of the patients.

Majority of the patients were in moderate DUKE risk subgroup [Table 6] and there was no statistically significant difference between males and females in this regard.{Table 6}

 Discussion



Exercise stress testing is presently used to assess physical fitness, determine exercise capacity, diagnose cardiac disease, define the prognosis of known cardiac disease, prescribe an exercise plan, and guide cardiac rehabilitation. [17] Exercise treadmill test is one of the various ways by which a patient's exercise capacity can be assessed. It had been demonstrated that a woman's inability to reach a MET level of 5 was associated with a 3.1-fold increase in the risk of death compared with MET levels >8, and that asymptomatic women whose exercise capacity was <85% of the age-predicted value had twice the risk of death from cardiac causes than those whose exercise capacity was ≥85% of the age-predicted value. [18] As expected, the females in our study had a lower exercise capacity, measured in METs, than their male counterparts. This gender difference in exercise capacity is well-described in published data and is attributed to the higher body fat composition, lower hemoglobin content, and smaller heart size of women. Again, a decreased peak stroke volume associated with female gender had also been associated with a reduced exercise capacity. [7] Interestingly, this gender difference in exercise capacity was not associated with a difference in exercise efficiency either at baseline or after training, unlike what obtains in the elderly where a decreased exercise capacity is associated with decreased exercise efficiency. Thus, the gender-related differences in exercise capacity may largely be explained by gender-related differences in cardiovascular hemodynamic factors such as peak heart rate and stroke volume. [19]

The linkage between exercise capacity and left ventricular diastolic function is also well established. [20] There is an association between left ventricular diastolic dysfunction and exercise performance in patients without [20] and with [21] type 2 diabetes. Subjects with impaired left ventricular diastolic dysfunction have been found to have reduced exercise capacity. Though left ventricular functions were not assessed in our study, previous reports have shown that the absolute reduction in exercise capacity in women compared with men is similar across the spectrum of diastolic dysfunction, suggesting that diastolic parameters do not account for the sex differences in exercise capacity. [22]

We also examined the effect of autonomic function on this gender difference in exercise capacity in our diabetic subjects. Though female diabetics in this study had higher resting heart rate, this became blunted when compared with male counterparts at the peak of exercise. There was also no significant difference in the heart rate reserve and the number of males who achieved at least 85% maximum age-predicted heart rate with exercise compared with females. In short, there was no significant gender difference in chronotropic response to exercise in our study. However, HRR was faster in males than females and in discrete term, more females had abnormal HRR compared with females. The pathophysiology of abnormal HRR and chronotropic response is not fully understood. Both HRR and chronotropic response appear to measure the autonomic response to exercise, abnormalities of which have been demonstrated to independently predict adverse cardiac outcomes. [16],[23] Predisposition to fatal arrhythmias, sudden cardiac death, and significant coronary artery disease has been postulated as potential mediators of these outcomes. [4],[24] HRR appears to measure the capacity of the cardiovascular system to reverse the vagal withdrawal that occurs during exercise. [25],[26] Abnormalities in this reversal, as indicated by abnormal HRR, are associated with mortality in asymptomatic patients, patients….…undergoing coronary angiography, stress echocardiography, and nuclear perfusion imaging. This association is independent of left ventricular systolic function and severity of coronary artery disease. Chronotropic response on the other hand appears to assess the autonomic response to exercise. Abnormalities in this response may indicate disruptions in autonomic balance and an inability of the cardiovascular system to respond appropriately to the sympathetic discharge and parasympathetic withdrawal that occurs during exercise. [27]

Increased resting heart rate itself may reflect autonomic dysfunction, especially dysfunction in parasympathetic nervous system. Patients with high parasympathetic activation usually have low resting heart rate and baseline oxygen consumption and may achieve high workload for a certain level of oxygen consumption. Physiologically, exercise results in prompt withdrawal of vagal tone and subsequent sympathetic activation, while recovery is associated with parasympathetic activation followed by sympathetic withdrawal. HRR correlates with vagal activity. [25],[26] Previous studies have shown that reduced HRR is associated with type 2 diabetes. [28] The present study further showed that the reduced HRR is more in females than males. Taken together, the higher resting heart rate and slower HRR may reflect a more serious damage to parasympathetic nervous system in female diabetics compared with male diabetics. That an abnormality in HRR correlated with exercise capacity in our study is consistent with previous studies. [29] The fact that exercise training improves both autonomic function and exercise capacity in type 2 diabetes [30] is noteworthy. This should encourage physicians to emphasize the need for exercise training as part of management strategies to reduce morbidity and mortality in type 2 diabetes.

Peak exercise SBP was significantly higher in the male than the female subjects in our study. Type 2 diabetes is associated with reduced LV systolic volume, altered myocardial and diastolic functions, and increased arterial stiffness, [31],[32] which are important parameters related to BP regulation and equally potential contributors to the reduced exercise capacity documented in diabetic individuals. How then does one explain the higher pSBP in the male subjects and their observed better exercise capacity compared with female diabetics seen in our study?

A likely explanation could be that a relatively more important LV remodeling, [33] induced by diabetes and triggered more specifically by arterial stiffness, [31] might be present and induce a transitory adaptive beneficial impact such as a higher cardiac output before the appearance of diastolic dysfunction in subjects with higher exercise SBP compared with subjects with lower exercise SBP. This might override the deleterious impact induced by diabetes on left ventricular function. To buttress this argument, a positive relationship has been reported between a nonpathological left ventricular hypertrophy with a preserved diastolic function [34] and elevated exercise SBP and exercise capacity in athletes. [35] However, this positive influence on exercise capacity is probably lost with the appearance of diastolic dysfunction. [21]

Lastly, the DTS has been recommended by the American College of Cardiology and the American Heart Association as a tool for post-test cardiac risk stratification. [5] The use of multivariable statistical techniques to estimate probability of cardiac events or angiographic findings has led to several valid scores. The most universal of these tests is the DTS. Considering the likelihood that a large number of diabetic patients will have obesity, hypertension, peripheral vascular disease, peripheral neuropathy, physical deconditioning, and decreased exercise capacity, which are factors that may influence the ability of the patients to exercise long enough to achieve a workload adequate to induce ischemia and its related symptoms and electrocardiogrphic findings, significant coronary artery disease may be present but remain undetected. As a result, these individuals may fall into the low or intermediate DTS range erroneously as may have been the case in our present study where majority of the patents fell into the intermediate DTS, despite the fact that exercise was terminated in majority of the patients as a result of fatigue and not reported chest pain. They therefore may be wrongly managed conservatively, similar to their nondiabetic counterparts. Lakkireddy et al. [5] demonstrated the clinical value of the DTS in the risk stratification of nondiabetic and diabetic patients. They noted a strong association between DTS and the combined outcomes of cardiac death, nonfatal myocardial infarction, congestive heart failure, and revascularization in both nondiabetic and diabetic patients.

A major limitation of this study was the small sample size and non-measurement of glycated hemoglobin of the patients which assesses glycemic control over a longer period of time than FPG.

 Conclusion



Gender difference occurs in the exercise capacity of diabetic patients. The factors associated with this difference may be related to gender differences in resting heart rate and HRR, both reflecting a withdrawal of vagal tone. The need to prescribe exercise as part of the management strategies in type 2 diabetes is well established, but then, not until appropriate cardiac risk stratification has been done with a noninvasive method such as exercise stress test.

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