Over the centuries, many theories on chronic disease prevention have come and gone, but one recommendation has stood the test of time: a physically active lifestyle is a key behavior required for optimal health and disease prevention. The importance of physical activity in cardiometabolic diseases such as type 2 diabetes (T2D) prevention and treatment has been recognized for centuries, and two decades have passed since the publication of clinical evidence from large outcome-driven randomized clinical trials supporting the notion that increasing physical activity levels confers protection against the onset of T2D (13). Results from these lifestyle intervention studies support those derived from large observational cohorts suggesting an inverse relationship between self-reported physical activity levels and long-term T2D risk (46). As a result, most guidelines not only for T2D prevention but also for cardiovascular disease (CVD) or nonalcoholic fatty liver disease prevention recommend achieving a certain amount of physical activity, such as 150 min of moderate to vigorous physical activity per week via aerobic or resistance training or both (7,8). While randomized clinical trials have been helpful to establish a causal role of physical activity on cardiometabolic disease prevention, many scientific questions remain, including the “dose” of physical activity for optimal T2D risk reduction. Unfortunately, this issue has not yet been answered by large outcome-driven randomized clinical trials. To provide clear and concise messages to our policy makers, health professionals, and the general public, further data from large and rigorous studies with an adequate assessment of physical activity minutes, intensity, and volume are needed. However, a large proportion of observational studies published to date have relied on self-reported physical activity level. Studies using objective measures of physical activity–associated energy expenditure (PAEE) usually have had limited sample size, making it difficult to appropriately evaluate the health benefits of various physical activity modalities.

In the early 2000s, the U.K. government, via the Medical Research Council, the Wellcome Trust, and the Department of Health, began funding the UK Biobank, a prospective cohort including hundreds of thousands of deeply phenotyped U.K. participants with anonymized data that have been made available to scientists from all over the world. Two decades after the launch of this study, the UK Biobank has become an inspiring example of data generating and sharing in health research. Among the plethora of phenotypes assessed in UK Biobank participants, questionnaire- and accelerometer-based assessments of physical activity habits were obtained in a subgroup of nearly 100,000 participants. Such a large study represented an unprecedented opportunity to further explore an important question, such as the optimal “dose” of directly measured physical activity to prevent the onset of cardiometabolic diseases such as T2D.

Figure 1

Implementing population-based and individual approaches to increase daily physical activity energy expenditure may provide cardiometabolic benefits and decrease long-term risk of age-associated health outcomes such as type 2 diabetes. In the study by Strain et al. (10), a dose-response effect of daily physical activity volume and intensity and T2D risk in 90,096 participants of the UK Biobank was observed. These results suggest that individuals should be encouraged to increase daily PAEE for optimal cardiometabolic health and lower risk of T2D. Other UK Biobank analyses revealed possible effects of a higher daily PAEE on other age-associated health outcomes that are listed in the figure. It should be emphasized that individuals with a higher daily PAEE do not differ from people with a lower daily PAEE only by their personal will or awareness of the health benefits of physical activity. The presence of systemic barriers to physical activity may explain the large interindividual PAEE differences in the population. The systemic barriers that prevent individuals from engaging in daily physical activity and other lifestyle behaviors associated with cardiometabolic health are also presented. These barriers will also need to be addressed to increase physical activity habits and reduce the societal burden associated with T2D.

Figure 1

Implementing population-based and individual approaches to increase daily physical activity energy expenditure may provide cardiometabolic benefits and decrease long-term risk of age-associated health outcomes such as type 2 diabetes. In the study by Strain et al. (10), a dose-response effect of daily physical activity volume and intensity and T2D risk in 90,096 participants of the UK Biobank was observed. These results suggest that individuals should be encouraged to increase daily PAEE for optimal cardiometabolic health and lower risk of T2D. Other UK Biobank analyses revealed possible effects of a higher daily PAEE on other age-associated health outcomes that are listed in the figure. It should be emphasized that individuals with a higher daily PAEE do not differ from people with a lower daily PAEE only by their personal will or awareness of the health benefits of physical activity. The presence of systemic barriers to physical activity may explain the large interindividual PAEE differences in the population. The systemic barriers that prevent individuals from engaging in daily physical activity and other lifestyle behaviors associated with cardiometabolic health are also presented. These barriers will also need to be addressed to increase physical activity habits and reduce the societal burden associated with T2D.

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In this issue of Diabetes Care, building on their previous work on the impact of wearable device–measured physical activity and health risk (9), Strain et al. (10) present the results of a prospective UK Biobank investigation into PAEE and incident T2D. The investigators first estimated PAEE based on data from a wearable device worn on the wrist for 7 days (a method validated against the gold standard stable isotope measurement) in 90,096 UK Biobank participants without T2D. During the follow-up, 2018 individuals received a diagnosis of T2D. A remarkably linear inverse relationship between PAEE and T2D risk was found. The authors then proposed that a PAEE equivalent to a 20-min brisk walk could reduce the risk of developing T2D by almost 20%. Additional low-intensity physical activity was associated with even lower odds of T2D, while higher-intensity activity appeared to provide additional benefits at a given amount of PAEE. These findings were consistent in both sexes and in older versus younger participants.

Taken together, results of this study suggest that when it comes to physical activity for T2D prevention, some is better than none, more is better, and earlier is best. Benefits of physical activity are observed across the adult life span. Thus, achieving a higher daily physical activity volume and higher intensity at any volume both may be important to minimize the risk of T2D. Of note, a higher volume of physical activity can also be achieved by adhering to a physically active lifestyle early in life. For those who were sedentary in their young adult life, the study suggests that it is never too late to become physically active to reduce the risk of T2D.

Interestingly, this dose-response effect is not observed with all cardiometabolic diseases, for instance, with CVD. Using a similar approach, the authors reported an important impact of achieving a minimal volume of PAEE but a more modest effect of increasing the dose of physical activity on CVD prevention (11). Physical activity intensity was, however, more linearly associated with CVD risk, suggesting that strategies based on increasing physical activity volume and intensity depending on individual preferences may prevent the onset of a broad range of cardiometabolic diseases.

This study may also provide important new insight into the pathobiology of T2D. For example, the authors reported large absolute differences across all BMI categories and that the BMI slightly mediated the relationship between higher PAEE and lower T2D risk. Although the relationship between PAEE and body weight was modest overall, a high daily PAEE may have important effects on daily energy turnover and partitioning as well as on body fat distribution. A high PAEE generates glycogen depletion, leading to increased glucose storage space, and improves insulin sensitivity (1214). Increased glucose uptake and oxidation in lean tissues such as skeletal muscle and liver relieves the pressure on adipose tissue for unused energy storage, improves adipose tissue storage capacity and thermogenesis, and lowers inflammation, which are all factors contributing to T2D risk reduction (15). Mobilization of “ectopic” lipids from the skeletal muscles, liver, pancreas, and/or abdomen could also contribute to alleviation of peripheral insulin resistance and improved β-cell function (15). Such metabolic improvements associated with more physical activity may not necessarily require substantial loss of body weight in some individuals, which explains why physical activity and exercise can prevent the onset of T2D even in the absence of BMI changes (16,17) (Fig. 1).

These findings should encourage clinicians to 1) inspire their patients who are capable to engage in daily physical activity, regardless of their weight status, 2) recognize the limitations of BMI for the assessment of overall metabolic or health status, 3) assess physical activity level as well as diet or sleep quality as “lifestyle vital signs,” and 4) promote healthy lifestyles in everyone, regardless of the impact of such interventions on body weight (18,19). An active lifestyle first should be promoted for health rather than as a weight loss strategy.

Limitations of this important study are acknowledged by the authors themselves (10). Of course, causality cannot be inferred from an observational study design. In addition, physically active people do not differ from people who are more sedentary simply because of their personal will or awareness of the health benefits of physical activity. Dozens of socioeconomic and environment-related factors also influence population levels of physical activity and health hazards. From urban design, road safety, and public transportation policies to the way our families, schools, workplaces, and communities are organized and funded, many factors that are out of our individual control shape our daily physical activity habits, whether we live in urban, suburban, or rural areas. Many children and adolescents do not have equal opportunities of living engaged in organized sports or of access to recreational physical activities. Major socioeconomic disparities exist regarding access to resources and environments permissive to an active lifestyle. Thus, social factors influence both physical activity habits and disease trajectories, and they will need to be tackled if we want to be successful in the promotion of a sustainable physically active lifestyle (20). Addressing the environmental and systemic barriers to physical activity should be among our top priorities if we want to dampen the progression of T2D.

See accompanying article, p. 1145.

Funding. B.J.A. holds a senior scholarship from the Fonds de Recherche du Québec–Santé (FRQ-S) and is supported by grants from the Canadian Institutes of Health Research (CIHR) and the Foundation of the Quebec Heart and Lung Institute. J.-P.D. is the scientific director of the International Chair on Cardiometabolic Risk, supported by the Fondation de l’Université Laval, and is the cochair holder of the Chaire de Recherche en Santé Durable funded by FRQ-S. Research from J.-P.D. is currently supported by the CIHR (foundation grant FDN-167278).

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

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