Physical activity and T2DM

Numerous studies have shown that low physical activity levels are adversely associated with metabolic risk factors, including measures of glucose homeostasis. Large clinical trials have shown that increased physical activity reduces the risk of developing type 2 diabetes by 15-60%. Correspondingly, the amount of time spent in sedentary activities has been found to be positively associated with a less healthy glucose metabolic profile. The overall pathophysiological mechanisms underlying the beneficial effects of physical activity on glucose metabolism appear due to the effect of increased physical activity in causing increased peripheral insulin sensitivity, leading to increased muscular glucose uptake. Increased physical activity levels may in addition cause increased beta cell function, leading to increased insulin secretion.

Physical activity

Physical activity can be defined as ’any bodily movement produced by skeletal muscles that results in energy expenditure’ and refers to physical activities performed during daily life, for example, at work, and during leisure time. Physical activity is not to be confused with ‘exercise’ which is just a part of overall physical activity, and refers to planned and structured bodily movement, often with the aim of improving or maintaining physical fitness components.

Physical activity is a complex and multidimensional behavior that includes type (e.g. aerobic or muscle-strengthening), total volume of physical activity (covering frequency, intensity, and duration of the physical activity bouts), and the context in which physical activity is performed. The total volume of physical activity performed can be expressed as the ‘physical activity energy expenditure’, which is the physical activity induced energy expenditure, and is most often measured in kilojoules or kilo-calories per time unit, taking into account bodyweight. Another way to quantify physical activity is to describe the intensity with which the physical activity is performed, combined with the duration of the task.

Traditionally, epidemiological studies have classified physical activity intensity into different intensity categories using cut-points based on metabolic Figure 1. The movement continuum: illustrating different physical activity intensities. METs= metabolic equivalent tasks. SB= sedentary behavior.
Figure 1. The movement continuum: illustrating different physical activity intensities. METs= metabolic equivalent tasks. SB= sedentary behavior.
equivalents (METs, defined as multiples of the resting metabolic rate) for specific activities, derived from different laboratory studies. The activity intensity is illustrated in the ‘movement continuum’ (Figure 1), ranging from sleep to vigorous physical activity intensity.

Physical activity and glucose metabolism

In experimental studies, the physiological pathways linking exercise bouts with increased insulin sensitivity and glucose uptake is suggested to include Figure 2. Simplified figure of the muscle contraction-mediated translocation of glucose transporter protein 4 (GLUT4) to the cell membrane and glucose uptake
Figure 2. Simplified figure of the muscle contraction-mediated translocation of glucose transporter protein 4 (GLUT4) to the cell membrane and glucose uptake
increased capillarisation, oxidative capacity of the mitochondria, and increased glucose transporter 4 protein, GLUT4 [1]. After contraction of the skeletal muscle, a cascade reaction (Figure 2) leading to translocation of GLUT4 to the cell membrane is started. In addition to increasing insulin sensitivity, exercise training has been suggested to be associated with an increased insulin secretion in patients with type 2 diabetes and with a decrease in healthy persons [2].

Frequency, duration, and intensity

Duration of the physical activity is thought to be one of the primary factors that influence the response of insulin action to exercise training [3], but the intensity, as well as the frequency of exercise bouts, seems to influence insulin sensitivity. The effect of exercise on insulin sensitivity has been found to last up to 48 hours, which has been the background for recommending regularly physical activity to improve glucose homeostasis.

Most studies investigating the association of physical activity with glucose metabolism has included measures of moderate-to-vigorous physical activity due to the health beneficial effects of the higher physical activity intensities. In cross-sectional and prospective studies, physical activity of moderate-to-vigorous intensity, has been related to better glucose homeostasis [4], whereas other studies have found overall physical activity to be the main determinant of insulin sensitivity [5].

Recent studies have investigated the association of light physical activity with glucose metabolism and more time spent with light physical activity is, in some studies, positively associated with insulin sensitivity and negatively associated with insulin concentration two hours after a glucose load [6]. This indicates that even small increments in physical activity levels are associated with a better glucose metabolic profile.

However, there does seem to be a dose-response relationship of the association of physical activity with glucose metabolism, so that the higher the total volume, the better the glucose metabolic profile. Results from large epidemiological studies show that vigorous physical activity performed at work might not be associated with a better glucose metabolic profile. Thus, the context of physical activity (e.g. performed during leisure time or at work) also seems to be an important factor.

Context of physical activity

While most studies suggest leisure time physical activity to be beneficial for health glucose metabolism, some discrepancy in determining the direction of the association of occupational physical activity with cardio-metabolic risk factors exists. The hypothesis of a u-shaped curve between occupational physical activity and metabolic risk factors is somewhat supported by recent findings from a large Scandinavian study [7].

Compared to persons with an occupational physical activity level characterized as ‘sedentary’, persons with an occupational physical activity level characterized as ‘moderate’ had lower insulin resistance (as compared to persons with sedentary levels), whereas those that had a ‘high’ occupational physical activity level had higher levels of insulin resistance compared to those in the sedentary category [7]. It is worthy of note that these associations were seen even after adjusting for educational attainment. As such, the accumulation of physical activity throughout the day and type of physical activity (e.g. bending the back, lifting heavy things) might be an important factor in relation to specific health outcomes, including glucose metabolism.

Sedentary behavior

In modern societies, the time spent with sitting activities is increasing, and an increasing number of studies have focused on the deleterious health consequences of prolonged sitting. Even for persons meeting the recommended physical activity level of 30-minutes moderate-to vigorous physical activity per day, sedentary behavior is adversely associated with the glucose metabolism [8]. Accelerometer-assessed sedentary behavior has been found to be adversely associated with insulin concentration and with hepatic insulin resistance, and questionnaire-assessed sedentary time with plasma glucose levels two hours after an oral glucose tolerance test (2-hour plasma glucose).

Additionally, breaking up sedentary time has been shown to be beneficially associated with 2-hour plasma glucose levels. Furthermore, television viewing time (a widely used marker of sedentary behavior) has been shown to be adversely associated with fasting and 2-hour plasma glucose levels, with cardio-metabolic risk and with death [9].

The underlying mechanisms of the deleterious associations of sedentary behavior with glucose metabolism are to be elucidated. However, results from animal studies suggest that decreased contractile stimulation of skeletal muscles while being inactive results in a reduced glucose uptake through reduced translocation of GLUT4 to the cell surface.

Effects of increasing physical activity – the public health perspective

Although lifestyle interventions aiming at increasing physical activity have shown to be a promising way of delaying the pathophysiological changes that leads to diabetes [10], results from the LOOK AHEAD study did not find any effect of physical activity on cardio-vascular events or mortality, which are the main complications of diabetes. In patients with diabetes, the study evaluated the effect of an intervention (increasing moderate physical activity to at least 175 minutes per week) on cardiovascular events or mortality [11] and found no differences in primary end-points (cardio-vascular events or death) between the intervention and the control group over the ten years of follow-up. However, the intervention group had significantly lower levels of glycated hemoglobin than the control group. Furthermore, medication usage (such as antihypertensive drugs, statins and insulin) was significantly lower in the intervention group as compared to the control group. As such, physical activity can work as a tool to lower medication and to maintain glycemic control in patients with diabetes.

Even though the effect sizes of the associations of physical activity with components of glucose metabolism is often small, increasing physical activity level and decreasing time spent sedentary will have a potential large effect on the population level, and thus, will, in addition to other lifestyle modifications, lower the risk of development of type 2 diabetes.

Since physical activity intensity should be seen as a continuum, decreasing sedentary behavior will inevitably leave more time for other physical activities. For some persons, increasing the amount of light physical activity might be a more realistic approach rather than increasing physical activity of moderate-to-vigorous character. Another way of increasing physical activity levels by relatively small changes are by ‘high intensity training’ (or HIT). In HIT, short periods of high intensity physical activity are implemented repeatedly into light or moderate activity (in example while walking or cycling). This has shown to be a promising way of increasing overall physical activity level, cardio-respiratory fitness, and glucose uptake [12].

Future studies will provide important insights into the link between physical activity and diabetes due to the rapid and continuous development of new methods to obtain precise and reliable direct measures of physical activity, in ‘real-life’ settings.

See also: Prevention of T2DM: Physical exercise


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