Introduction
Moderate- to vigorous-intensity exercise is one of the cornerstones of prevention and treatment of type 2 diabetes [
1,
2], with current physical activity guidelines recommending performance of at least 150 min/week exercise at these intensities [
3]. Although this approach has proved effective in the prevention [
4] and treatment [
5] of type 2 diabetes, more than 90% of healthy adults do not adhere to these guidelines [
6]. In view of type 2 diabetes-related comorbidities such as muscle weakness and peripheral neuropathy, which can be a barrier to physical activity [
7], non-compliance may be even higher in individuals with type 2 diabetes. Alternatives to exercise are therefore needed for the treatment of type 2 diabetes.
The results of population-based studies suggest that the average adult spends more than half of the waking day sedentary, partaking in activities such as watching television and using the computer [
8‐
10]. Recent evidence from observational studies shows an association between sedentary time and an increased risk of type 2 diabetes, independent of the time spent exercising [
8,
10]. Experimental studies under laboratory conditions suggest that regular interruption of sitting using small bouts of walking may be effective in lowering glucose and insulin levels in healthy and overweight/obese adults and in individuals with type 2 diabetes [
11‐
15]. We recently showed that replacing sitting time with standing and light-intensity walking in free-living conditions was more efficient at improving insulin action than replacement with one bout of moderate- to vigorous-intensity exercise (cycling) in healthy sedentary participants [
16]. Since energy expenditure was comparable by design during these two conditions, these data suggest that sitting has negative effects on insulin sensitivity independent of energy expenditure.
To investigate whether these findings could be replicated in individuals with type 2 diabetes, we investigated whether, under conditions of comparable energy expenditure, breaking up sitting time with standing and light-intensity walking would improve 24 h glucose levels and insulin sensitivity in type 2 diabetes patients as compared with structured exercise. To our knowledge, this is the first study investigating the glycaemic effects of breaking up sitting time in people with type 2 diabetes in free-living conditions.
Results
After screening, 20 participants (14 men, six women) were included in the study (see electronic supplementary material [ESM] Fig.
1 for recruitment flow chart). Before completing the protocol, one participant withdrew because of osteoarthritis-related pain during walking. The remaining 19 individuals had a mean age of 63 years and a mean BMI of 30.5 kg/m
2 (Table
1). The median duration of type 2 diabetes was 6 years and participants had a mean HbA
1c of 6.7% (49.5 mmol/mol) and mean fasting plasma glucose of 7.88 mmol/l during screening (Table
1). Fourteen participants were using oral glucose-lowering drugs (metformin,
n = 14; sulfonylurea,
n = 7; sitagliptin,
n = 2), and 13 were using lipid-lowering drugs (statins,
n = 12; ezetimibe,
n = 2).
Table 1
Participant characteristics
N
| 19 |
Men (n) | 13 |
Age (years) | 63 (9) |
Duration of type 2 diabetes (years)a
| 6 (4, 10) |
Glucose-lowering drugs (n) | 14 |
Lipid-lowering drugs (n) | 13 |
Height (m) | 1.70 (0.07) |
Weight (kg) | 88.8 (12.0) |
BMI (kg/m2) | 30.5 (3.3) |
Waist circumference (cm) | 105 (8) |
Wmax (W) | 152 (43) |
Systolic BP (mmHg) | 143 (12) |
Diastolic BP (mmHg) | 82 (8) |
Glucose (mmol/l) | 7.88 (1.51) |
Triacylglycerol (mmol/l) | 1.51 (0.55) |
HbA1c (%) | 6.7 (0.8) |
HbA1c (mmol/mol) | 49.5 (8.8) |
Discussion
Structured exercise is a recognised cornerstone of type 2 diabetes treatment and prevention. However, sustained compliance with exercise programmes, especially by individuals with type 2 diabetes, is at best mediocre [
26,
27]. Observational studies have revealed associations between the time spent sitting and markers of metabolic disturbance [
8‐
10]. Therefore, reducing the sitting time may improve glycaemic control and insulin sensitivity in type 2 diabetes. Strategies to reduce sitting time are generally considered to be less demanding than structured exercise programmes and hence are more likely to have long-term compliance [
28]. In this study, we observed that the Sit Less regimen improved insulin sensitivity, mean 24 h glucose levels, 24 h glucose excursions, duration of hyperglycaemia (blood glucose ≥10 mmol/l) and fasting triacylglycerol levels.
We used a proof-of-concept study to determine the relative efficacy of reducing sitting time or increasing structured exercise. As a result, the number of steps during Sit Less (around 17,500 steps/day) was well above what is generally observed in patients with type 2 diabetes (around 6500–8000 steps/day) [
7,
29] and, therefore, the duration/intensity of exercise was also high (65 min/day cycling at 5.9 MET) and probably not sustainable on a long-term basis. The beneficial effects of Sit Less were observed in participants with type 2 diabetes, the majority of whom were men using oral glucose-lowering medication (the use of which was continued throughout the study duration). Subanalyses showed similar improvements in 24 h glucose iAUC during Sit Less in participants who were not taking glucose-lowering medication (
n = 5), as well as for women only (
n = 6).
The outcome of the present study fits the emerging picture that breaking up sedentary behaviour by light-intensity activities may help to improve glucose homeostasis in groups, ranging from young lean normoglycaemic individuals [
16] to overweight/obese normoglycaemic [
13] and dysglycaemic [
14] participants. Very recently, Dempsey et al showed that breaking up sitting time with brief bouts of light-intensity walking or resistance exercise attenuates postprandial glucose and insulin responses in type 2 diabetes [
12]. In the current study, the general effect of the Sit Less regimen on glucose homeostasis tended to be a little more potent than the effect of structured exercise. One of the effects of acute exercise on elevated blood glucose in diabetes is a post-exercise reduction in glucose levels; this can sometimes result in hypoglycaemia and can render some diabetic patients reluctant to perform structured exercise. In our study, the Sit Less regimen did not result in glucose level reductions at 30 min compared with the Sitting regimen, whereas 30 min glucose levels fell by more than 5 mmol l
−1 h
−1 during the Exercise regimen. These data suggest that more stable glucose levels can be achieved with light-intensity activity rather than with exercise.
For most variables, other than 24 h glucose, the structured exercise regimen (Exercise) had beneficial effects. The effect size of Exercise, however, was typically intermediate compared with the effects of Sit Less and was only greater for the increases observed in fasting plasma NEFA levels vs Sitting. These results are in line with a recent study by Henson et al showing that breaking up sitting time with walking or standing increased NEFA levels in overweight/obese postmenopausal women [
14]. Although the mechanism underlying the increase in NEFA concentration after Sit Less and Exercise is incompletely understood, it probably reflects a spill-over of fatty acids from increased adipose tissue lipolysis used to fuel contractile activity. Upon cessation of contractile activity, the amount of fatty acids taken up by the muscle for oxidation decreases more promptly than the catecholamine-induced elevation of adipose tissue lipolysis, resulting in elevated plasma NEFA levels [
30]. In contrast to our previous study in healthy volunteers [
16], we failed to observe significant effects on cholesterol levels in individuals with type 2 diabetes. The most likely explanation for this apparent discrepancy is the fact that participants stopped lipid-lowering medication 2 weeks prior to the study, a period that may have been too short.
Both Sit Less and Exercise resulted in lower fasting plasma triacylglycerol levels, which may be the result of increased triacylglycerol clearance due to enhanced lipoprotein lipase activity [
31]. These observed lower triacylglycerol levels after physical activity are in line with previous [
16,
31] but not all [
15] studies. In the latter study, however, triacylglycerol levels were probably measured too soon after exercise, as lipoprotein lipase activity typically peaks ≥8 h post exercise.
In line with our previous study in healthy individuals [
16], we observed that insulin sensitivity was more greatly improved after the Sit Less regimen than after the Exercise regimen. This finding may seem surprising given the high dose of exercise (65 min/day cycling at an intensity of 5.9 MET). It is possible that HOMA-IR was not accurate enough to detect relatively small changes in insulin sensitivity after Exercise. However, it should be noted that, during the Exercise regimen, participants spent most of the day sitting. We observed similar findings in healthy individuals [
16] and we therefore suggest that one bout of exercise probably cannot fully compensate for the negative effects of sitting for the rest of the day. Thus, the duration of non-sitting activities may be more important than the intensity of these activities. Since the participants were instructed to break up sitting time every 30 min, this may have contributed to the beneficial effects observed during Sit Less in comparison with Exercise. However, the activPAL programme did not provide information on the duration of sitting bouts; therefore, this behavioural outcome could not be well assessed. Energy expenditure was expressed in METs by the activPAL; for the sake of comparison, we also converted the external workload on the stationary bike to MET values. Although we appreciate that the conversion of measured power output to predicted MET values is a proxy for the actual energy expenditure, we believe that this method is valid when it comes to comparing the energy expenditure in Sit Less with Exercise.
In conclusion, this study suggests that breaking up sitting time by promoting time spent standing and light-intensity walking is a potent way to beneficially affect insulin resistance and other clinically relevant markers of glucose metabolism, and plasma triacylglycerols in individuals with type 2 diabetes who are taking oral glucose-lowering medication. Although an approximate energy-matched intervention with structured exercise also displayed most of the beneficial effects of breaking up sitting time, the present study provides indications favouring the implementation of interventions targeting the breaking-up of sitting time over interventions involving structured exercise. The effect of breaking up sitting time on insulin resistance was more pronounced than that of structured exercise. Additionally, the more abrupt and prominent reduction in blood glucose in the structured exercise intervention is proposed to increase the risk of hypoglycaemia [
32]. Since the volume of activities in this proof-of-concept study was high, future long-term studies are needed to determine the volume of light-intensity activities that is feasible in daily life.
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