A moderate-intensity exercise program with a weekly duration not adherent to international guidelines improves blood glucose in women with type 2 diabetes

Introduction

Diabetes mellitus (DM) is a global health problem, with 537 million cases of DM were estimated worldwide in 2021 [1]. Type 2 DM is the most common type of DM and accounts for 90% of all cases of DM around the world [1]. This prevalence of DM is going to increase over the next years, with the greatest growth being in lowerincome countries [1]. In Egypt, the 10th highest ageadjusted diabetes prevalence worldwide was reported [2]. Women with type 2 diabetes have 25–50% increased risk of cardiovascular diseases (CVD) than diabetic men because women have a lower physical activity level and develop diabetes at a higher body mass index (BMI) than their male counterparts with diabetes, which means that women are subjected to excess body fatness and co-existing cardiovascular risks for a longer duration than men before developing type 2 diabetes [3].
Hyperglycaemia is a major risk factor for CVD and allcause mortality in patients with type 2 diabetes. Treatment interventions that reduce hyperglycaemia to nearnormal levels could prevent cardiovascular events and mortality of type 2 diabetic patients [4]. Exercise therapy is an effective intervention for normalizing blood glucose levels and reducing the risk of cardiovascular disease in patients with type 2 diabetes [5]. Current guidelines for the management of type 2 diabetes consider physical exercise training to be an essential component of the management plan, and recommend a minimum of 150 minutes up to 300 min of moderate-intensity activity per week [6]. However, many patients with type 2 diabetes, particularly obese women, may be unable to meet the recommended exercise volume because of reduced cardiopulmonary fitness [3], or because of time constraints owing to household activities or family commitments. Therefore, the purpose of this study was to investigate the effect of low-volume, moderate-intensity aerobic exercise training, defined as moderate-intensity exercise of < 150 minutes/week, on estimated average glucose in obese type 2 diabetic women. The results of this study may aid health professionals interested in exercise therapy of type 2 diabetes.

Material and methods

Ethical considerations

This study was conducted according to the Helsinki Declaration and approved by the Ethics Committee of Scientific Research of the Faculty of Physical Therapy at Cairo University (Approval No.: P.T.REC/012/004119). Patients gave their written consent prior to participation in this research.

Subjects

Twenty-two women with type 2 diabetes were recruited for this study. Patients were assigned to either an exercise group (n1 = 10) or a non-exercising control group (n2 = 12). For patient selection, a thorough medical history was taken, and patients were selected according to certain criteria. Inclusion criteria were type 2 diabetic women diagnosed by glycosylated haemoglobin (HbA1c) > 6.5%, age 30–50 years, obese patients with BMI > 30 kg/m2, and patients under oral hypoglycaemic agents. Exclusion criteria were male patients, pregnancy, patients with regular exercise habits, and/or patients with cardiopulmonary, neurological, or musculoskeletal limitations to exercise training. Patients in both groups received oral antidiabetic medications and maintained their usual lifestyle throughout the study. No dietary intervention was included in this study.

Measurements

Anthropometric measurements

Body weight, height, and waist circumference were measured at baseline. The body mass index (BMI) was calculated as BMI = body weight (kg)/height in metres squared.

Estimated average glucose

The glycosylated haemoglobin was measured for all patients, and the average blood glucose was estimated at baseline and after 8 weeks according to this equation: estimated average glucose [eAG] in (mg/dl) = 28.7 × HbA1c – 46.7 [7].

Incremental exercise test

Prior to exercise intervention, the eligibility for exercise testing/training was checked and a symptom-limited maximal treadmill exercise test was performed according to the modified Bruce protocol [8, 9]. Compared with the original Bruce protocol that has 5 stages and begins with a speed of 1.7 miles/hour at an inclination of 10% (stage 1), the modified protocol has 7 stages and starts at a zero inclination with a speed of 1.7 miles/hour (stage 0) and then increases to a 5% inclination at the same speed (stage 0.5) [9]. Patients underwent the test safely and stopped because of maximal exertion. The peak heart rate (HRpeak) was recorded immediately after the end of the test using a fingertip pulse oximetry. The baseline HRpeak was needed for the calculation of the target heart rate (THR).

Interventions

Exercise training intervention

The exercise training was prescribed to the patients in the intervention group using the “FITT” principle of exercise prescription laid down by the American College of Sports Medicine [10], as follows:
frequency – patients exercised for 3 days/week on alternate days;
intensity – the intensity of the working phase of exercise was set at a THR of 65–75% of HRpeak, determined from the incremental exercise test. The THR was monitored during exercise sessions by a fingertip pulse oximetry. The speed of the treadmill was adjusted to make the patients achieve their THR. A low intensity walking at a THR of < 60% HRpeak was set for the warm-up and cool-down phases of exercise;
time (duration) – the time of session was ≤ 45 minutes (5–10 minutes warm-up, 30 min working phase, and 3–5 min cool-down). The moderate-intensity exercise volume = frequency of sessions × actual duration of moderate-intensity exercising = 3 days/week × 30 minutes = 90 minutes/week, which is < 150 minutes per week. The total duration of exercise program was 8 weeks;
type/mode – continuous treadmill walking exercise.

Antidiabetic drug therapy

Patients in both groups were on oral hypoglycemic medication throughout the entire period of the study.

Statistical analysis

Unpaired t-test was used to analyse the data between the 2 groups at baseline. A paired t-test was used to analyse the changes in eAG means within each group after the intervention. A one-way ANCOVA test was used to assess the difference in the postintervention eAG means between the 2 groups after adjusting for the base­line differences in eAG means between the 2 groups [11, 12]. Descriptive statistics were used to present the data as means ± standard devision. P-values < 0.05 were considered statistically significant. GraphPad prism soft­ware was used for statistical analysis.

Results

The baseline age and anthropometric characteristics of the patients in the 2 groups are shown in Table 1. As shown in Table 1, there was no statistically significant difference in the anthropometric characteristics between the 2 groups. As shown in Table 2, there was a statistically significant reduction in average blood glucose compared to the baseline values in the exercise group only (paired t test, p < 0.001) (Fig. 1, Tab. 2). There was also a statistically significant difference in the eAG means between the 2 groups after the intervention in favour of the exercise group (ANCOVA test, p = 0.040) (Fig. 1, Tab. 2).

Discussion

The main findings of this study are as follows:
low-volume, moderate-intensity exercise (i.e. < 150 minutes/week) combined with oral hypoglycemic therapy induced a highly statistically significant reduction in estimated average blood glucose (eAG) compared tothe baseline value (p < 0.001);
the statistically significant improvement in eAG reported in the exercise group was clinically meaningful; the eAG reduced significantly from 187.3 ±18.29 to 147.7 ±10.50 mg/dl, which corresponds to a 1.4% reduction in HbA1c. For each 1% reduction in HbA1c there is an 18% reduction in cardiovascular risk [13] and a 37% decrease in micro-vascular complications [14] in patients with type 2 diabetes;
compared to the non-exercising control group, the low-volume, moderate-intensity aerobic exercise in addition to oral hypoglycemic medication induced significantly greater improvement in eAG in type 2 diabetic women.
Our results are supported by a recent meta-analysis by Pan et al. [15] which has shown that supervised aerobic exercises significantly reduced HbA1c and fasting blood glucose compared to no exercise. Our results are also consistent with a very recent study, which has shown that moderate aerobic exercises are capable of inducing significant improvements in blood glucose levels in type 2 diabetes [16]. In addition, a single session of moderate-intensity exercises was enough to produce a significant reduction in blood glucose in patients with type 2 diabetes, particularly in patients with excess body fatness and worse glycaemic control [17]. Furthermore, a cross-sectional study by Park et al. [18] showed that the moderate aerobic exercise can reduce the risk of poor glycaemic control by 0.317 times [18].
Physical exercise training stimulates muscle blood glucose uptake through insulin-dependent and insulinindependent pathways [19]. The cellular mechanisms responsible for exercise-induced glucose uptake could be as follows:
exercise-induced improvement in insulin sensitivity. Moderate-intensity exercise has been found to improve insulin sensitivity within skeletal muscles [20];
exercise-induced enhancement in mitochondrial function. Patients with type 2 diabetes have been shown to have damaged or dysfunctional mitochondria, which has been associated with insulin resistance [21]. Exercise training restores mitochondrial dysfunction found in type 2 diabetes partly due to increased mitochondrial content, which has been linked with enhanced insulin sensitivity and insulin-mediated glucose disposal [22];
exercise-induced increased availability, translocation, and expression of glucose transporter 4 (GLUT4). Aerobic exercise training has been reported to increase GLUT4 protein levels within the muscles [23]. Physical exercise is a potent stimulus to increase GLUT4 translocation and expression within skeletal muscles, contributing to improved insulin action and enhanced glucose disposal [24];
exercise-induced activation of 5’ adenosine monophosphate-activated protein kinase (AMPK). Muscle contractions increase AMPK activity – this enzyme plays a major role in stimulating blood glucose uptake by the working muscles [23, 25];
nitric oxide-mediated blood glucose uptake. Moderate-intensity exercise increases the bioavailability of nitric oxide [26], which plays an important role in the regulation of glucose uptake by muscles during exercise in patients with type 2 diabetes [24, 27]. Nitric oxide stimulates blood glucose uptake by skeletal muscles through modulation of blood flow (i.e. glucose delivery) or by regulation of intramuscular signalling involved in translocation of GLUT4 [28];
calcium (Ca2+) ion-induced glucose uptake. It has been reported that Ca2+ ions released during muscle contraction indirectly mediate glucose uptake through the increased energy expenditure needed for the action of Ca2+ pumps in the sarcoplasmic reticulum [23]. However, Jensen et al. [25] have suggested that sarcoplasmic reticulum Ca2+ plays no role in muscle contraction-stimulated glucose uptake;
exercise-induced increased muscle temperature could play a role in glucose uptake regulation. There is evidence suggesting that the increased muscle temperature can directly stimulate glucose uptake by the muscle, partly, through the activation of AMPK [29];
actin cytoskeleton reorganization within the muscles during physical exercise. The actin cytoskeleton is a composition of actin filaments with their accessory and regulatory proteins. The contraction/relaxation of muscle fibres during exercise leads to reorganization of the actin cytoskeleton, which modulates insulin signalling for GLUT-4 translocation, resulting in enhancement of glucose uptake by the muscles [19];
a potential role of exercise-induced hypoxia in the regulation of blood glucose uptake. Heinonen et al. [30] have shown that moderate hypoxia during exercise increased glucose uptake by the muscles; how­ever, this effect is yet to be confirmed;
exercise-induced adenosine triphosphate turnover and mechanical stress feedback signalling has also been found to stimulate skeletal muscle glucose uptake [25].
Interestingly, the remarkable reductions in average blood glucose seen in the exercise group, compared to the baseline and the control group, occurred without dietary co-intervention. This finding is consistent with the American Diabetes Association position statement, which has reported that supervised aerobic exercise training can reduce blood glucose levels in type 2 diabetic patients regardless of any dietary co-intervention [31]. Limitations of this study include the relatively small number of participants. Also, a few variables were measured; however, the exercise training protocol was designed based on an accurate and individualized determination of targeted exercise intensity using a symptom-limited maximal exercise test to record patients’ actual peak heart rate.

Conclusions

Complementary to oral antidiabetics, low-volume, moderate-intensity exercise, performed for less than 150 minutes/week, could be successful in inducing statistically and clinically significant reductions in average blood glucose in women with type 2 diabetes. This improvement can be attributed to exercise-mediated muscle glucose uptake through several cellular mechanisms recruiting insulin-dependent and insulin non-dependent pathways. This finding could be of great clinical relevance for obese patients with type 2 diabetes, particularly women unable to adhere to an exercise volume of ≥ 150 min/week as recommended by the current international guidelines, because of low functional capacity or lack of time to exercise. Future research work with a large sample size and both genders may be needed to confirm our findings.

The authors declare no conflict of interest.

References