Introduction
Lifestyle intervention programmes that combine regular exercise, dietary modulation and/or oral blood-glucose-lowering medication have proven an effective therapeutic strategy in type 2 diabetes [
1‐
3]. Continuous endurance-type exercise training has been shown to lower blood HbA
1c, increase insulin sensitivity, improve the risk profile for cardiovascular disease and reduce adipose-tissue mass in patients with type 2 diabetes [
4,
5]. In addition, exercise training represents the only interventional strategy that has consistently been shown to improve whole body and skeletal muscle oxidative capacity [
6]. In accordance, recently published standards of medical care for type 2 diabetes underline the importance of exercise prescription [
7].
However, the clinical guidelines do not include detailed information on the preferred exercise modalities that should be implemented to maximise the clinical benefits of exercise intervention in diabetes patients [
7]. Exercise intensity has been suggested to represent one of the more important exercise modalities that determine the clinical outcome of exercise interventions [
1,
4]. This has been attributed to the inverse relationship between exercise intensity and glycogen use within the muscle [
8,
9]. The magnitude of the increase in insulin sensitivity following an acute bout of continuous endurance-type exercise has been associated with the extent of muscle glycogen depletion and the subsequent repletion rate [
10,
11]. Whether such differences in the acute glucoregulatory effect of a single bout of exercise also translate into improvements in glycaemic control following more prolonged endurance-type exercise interventions in type 2 diabetes patients remains speculative [
12,
13].
Long-term exercise intervention studies investigating the impact of continuous low- to moderate-intensity (LI) vs high-intensity endurance-type exercise training on glycaemic control in healthy and/or glucose-intolerant individuals have reported high intensity exercise training to be, when compared with low-intensity endurance-type exercise training, less [
14], equally [
15,
16] or more [
17] effective. However, long-term exercise intervention studies in type 2 diabetes patients investigating the clinical benefits of either continuous LI or moderate- to high-intensity (HI) exercise training remain lacking.
The preference for implementing either an LI or HI exercise regimen in a continuous endurance-type exercise intervention programme for patients with type 2 diabetes is of great clinical relevance, especially when considering the inverse relationship between exercise intensity and patient compliance [
18]. As long-term patient compliance and adherence are required to improve glycaemic control effectively and reduce the prevalence of diabetes-related co-morbidities, it is essential to minimise patient dropout [
4].
Therefore, the present study compares the clinical benefits of continuous LI vs HI exercise training, matched for total energy cost, in obese type 2 diabetes patients. Changes in blood HbA1c content, indices of oral glucose tolerance and/or whole body insulin sensitivity, blood lipid profile, body composition, exercise performance and whole body and skeletal muscle oxidative capacity, as well as muscle fibre type composition, were assessed prior to and after 2 and 6 months of either continuous LI or HI endurance-type exercise training.
Discussion
In this study, the clinical benefits of 6 months of continuous LI vs HI endurance-type exercise training were assessed in obese type 2 diabetes patients. After 6 months of intervention, blood HbA1c content, body composition and whole body and skeletal muscle oxidative capacity had improved significantly, with no differences between the two groups.
It has been firmly established that regular exercise effectively lowers blood HbA
1c content in type 2 diabetes patients [
1‐
5]. In accordance, we observed a significant reduction in blood HbA
1c level following 2 and 6 months of exercise intervention in the obese type 2 diabetes patients (Table
2). It has been well established that the magnitude of the reduction in HbA
1c content following prolonged exercise intervention strongly depends on pre-intervention HbA
1c levels [
4]. In the present study, we observed a 0.3% reduction in HbA
1c level from the pre-intervention level of 7.2 ± 0.2%. This represents a clinically relevant decline and translates into a 6% reduction in the risk of premature death and an 11% reduction in the risk of microvascular disease [
21]. Furthermore, none of the participants had to increase oral blood-glucose-lowering medication within the 6 month intervention period. In contrast, six participants had to lower their medication dose. Though we confirm the benefits of exercise intervention to lower blood HbA
1c in type 2 diabetes patients, it still remains to be established which exercise training modalities should be applied to maximise the clinical benefits of exercise intervention [
1,
5]. Some suggest that (relatively) high intensity exercise activities are required to effectively improve glycaemic control [
8,
9]. However, others have failed to observe differences in the acute effects of a low-to-moderate vs a high intensity exercise bout on subsequent glycaemic control in type 2 diabetes patients, when exercise bouts were matched for total energy cost [
12,
13].
Surprisingly, long-term intervention studies investigating the impact of exercise intensity on the clinical benefits of exercise training in type 2 diabetes patients are lacking. Therefore, in the present study, we compared the impact of continuous LI with HI endurance-type exercise training, matched for total energy expenditure, in type 2 diabetes patients. Even though 6 months of endurance-type exercise training significantly lowered blood HbA
1c, this reduction did not differ between the groups undertaking the LI and HI exercise regimens (Table
2). Furthermore, no changes were observed in basal blood glucose and insulin concentrations and/or in the glucose response in the oral glucose tolerance tests. The present findings tend to be in line with previous observations of the acute effects of a low vs a high intensity exercise bout on glucose tolerance [
12,
13], and indicate that the implementation of continuous high intensity endurance-type exercise is not required to lower blood HbA
1c during more prolonged exercise intervention in obese type 2 diabetes patients. However, it should be noted that there is recent evidence showing that more intense interval-type exercise training is more effective than continuous-type exercise training in various metabolically and/or functionally compromised populations [
22‐
24]. However, the clinical benefits and feasibility of high intensity interval training remain to be established in type 2 diabetes patients.
The present findings suggest that prolonged continuous low-to-moderate-intensity exercise training is equally effective when compared with more intense exercise training as a means to lower blood HbA
1c content, when exercise bouts are being matched for total energy expenditure. This is of important clinical relevance, as patients with long-standing type 2 diabetes generally suffer from muscle weakness, cardiovascular co-morbidities and reduced exercise tolerance. Consequently, it has proven difficult to engage sedentary patients with type 2 diabetes in more intense exercise intervention programmes [
25]. As an inverse relationship exists between exercise training intensity and patients’ adherence to an exercise intervention programme [
18], it is not surprising that the implementation of a relative high intensity exercise regimen is generally associated with low patient adherence and higher dropout rates [
18]. In accordance, we observed a greater dropout rate from the HI group (
n = 8) than from the LI group (
n = 5), though this did not reach statistical significance (
p > 0.05). From the present findings, we conclude that the implementation of a continuous high intensity exercise programme is not required to lower blood HbA
1c content in obese type 2 diabetes patients. Consequently, a less intense continuous endurance-type exercise regimen can be equally effective when longer duration of exercise compensates for the lower exercise intensity.
Endurance-type exercise is generally implemented as the main type of exercise in diabetes intervention programmes to effectively reduce whole body fat mass. Historically, low-to-moderate intensity endurance-type exercise has been prescribed to maximise oxidation of skeletal muscle fat [
26] and thus maximise loss of fat mass. In the present study, we observed improvements in body composition, including an increase in skeletal muscle mass and a decline in body fat mass following 2 and 6 months of exercise intervention (Table
2). We observed a significantly greater reduction in trunk fat mass in the group undergoing HI exercise than in those undergoing LI training (Table
2). Although this may reflect a greater lipolytic response in adipose tissue during post-exercise recovery from more intense exercise [
27], the greater loss of trunk fat mass in the HI group was not accompanied by a measurable increase in oral glucose tolerance and/or whole body insulin sensitivity.
A low oxidative capacity of skeletal muscle has been associated with reduced fat oxidative capacity and greater risk of developing obesity, insulin resistance and/or type 2 diabetes. This has raised the question as to whether impaired mitochondrial function might represent an important factor in the aetiology of insulin resistance [
28]. In line with observations of differences in the morphological structure of skeletal muscle mitochondria in patients with type 2 diabetes [
28], reduced rates of expression of multiple nuclear respiratory factor-1-dependent genes have been reported in muscle tissue obtained from type 2 diabetes patients [
29]. Furthermore, studies applying
31P-magnetic resonance spectroscopy (MRS) with the intention to assess in vivo muscle mitochondrial function suggest the presence of impairments in mitochondrial function in insulin-resistant elderly men and the insulin-resistant offspring of people with type 2 diabetes [
30]. However, a significant limitation of these studies is that during the
31P-MRS measurements, O
2 flux was not normalised for mitochondrial content. When normalised, both oxidative phosphorylation and electron-transport capacity do not seem to be impaired in type 2 diabetes patients [
31]. Therefore, mitochondrial dysfunction does not represent a cause but rather a consequence of the obese insulin-resistant and/or type 2 diabetic state [
31,
32]. Prospective long-term training studies aiming to prevent or treat insulin resistance and type 2 diabetes are warranted to determine to what extent the proposed impairments in mitochondrial function can be remedied. In the present study, we observed increases in whole body oxygen uptake capacity (
\( \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} \): +16 ± 4%) and skeletal muscle oxidative enzyme activity (cytochrome
c oxidase: +56 ± 16% and citrate synthase: +46 ± 22%; Table
3) following 6 months of exercise training. As no interactions were observed within this timeframe, we conclude that continuous moderate-to-high intensity exercise training does not further augment
\( \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} \) or skeletal muscle oxidative capacity when compared with a less intense exercise regimen. Moreover, changes in
\( \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} \) and skeletal muscle oxidative enzyme activity did not correlate with the decline in blood HbA
1c levels. Interestingly, the continuous HI exercise regimen tended to result in a faster increase in
\( \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} \) during the first 2 months of the intervention programme. However, this was no longer apparent after 6 months of exercise training (Table
2).
In conclusion, despite a smaller decline in trunk fat mass, prolonged continuous moderate-to-high intensity endurance type exercise is equally as effective as low-to-moderate intensity exercise training at lowering blood HbA1c, elevating muscle mass and increasing whole body and skeletal muscle oxidative capacity in obese type 2 diabetes patients.