Focusing on Physical Activity,Not Body Weight,for the Control of Type 2 Diabetes

Human beings are built for physical activity. This is the key message I extracted, anyway, from Daniel Lieberman’s ¹ fascinating book Exercised. Regardless of its size or shape, the human body is a dynamic structure designed for movement. In addition to the discernible outcomes, such as locomotion and object manipulation, physical activity triggers numerous unseen effects, including the release of powerful signaling moieties throughout the body. These molecules, first dubbed “exerkines” in a 2016 paper, ² are increasingly viewed as pivotal contributors in the prevention and control of myriad diseases, including type 2 diabetes. ³

Although they do not employ the word “exerkines” expressis verbis, Adams and colleagues ⁴ focus our attention on the subcellular level in their analytic review of diabetes prevention in this issue of the journal. Their important article equips clinicians and population health specialists to rethink metabolic disease, transitioning from “visual and quantitative measures” to those that truly capture an individual’s health status. To question the validity of body mass index (BMI), and to suggest that its obsessive use may propagate weight stigmatization and body shaming, demonstrates intellectual curiosity and courage. BMI is the standard metric used in the United States ⁵ and around the world ⁶ for obesity assessment and control; its ubiquity as a screening tool has made it something of a third rail in epidemiology.

But Adams and colleagues are undeterred. In an engaging and comprehensive review, they promote a “paradigm change in how we think about weight and health.” ⁴ Insofar as physical activity is concerned, their paradigm is evidentially correct: Physical activity provides significant health benefits irrespective of one’s BMI. Numerous large-scale epidemiologic studies support their assertion, of which we will highlight just 3.

First, in a pooled meta-analysis with over 650K participants, Moore and colleagues found a dose-response relationship between physical activity and life expectancy at age 40 across 4 different BMI categories (18.5 to 24.9 kg/m² [normal]; 25.0 to 29.9 [overweight]; 30.0 to 34.9 [obese class I]; and ≥35.0 [obese class II]). Within each category, moderately active individuals lived longer than their inactive peers, and highly active individuals lived longer still. By stratifying by both BMI and physical activity level, the investigators uncovered an astounding pearl in the dataset: Compared to having a normal BMI and being highly active (defined as ≥7.5 MET-hours per week), having a normal BMI and being inactive resulted in more life lost (4.7 years) than having an obese BMI and being highly active (1.6 years for obese class I and 4.5 years for obese class II). In other words, as pertaining to longevity, physical activity engagement was more important than a weight-to-height ratio. Or in even simpler words—which happen to be those of the authors: “obese and active people may live longer than normal weight and inactive people.” ⁷

A second study deserves our consideration. Zhao and colleagues ⁸ examined nearly 480K adults in the National Health Interview Survey, who were followed for mortality outcomes as recorded in the National Death Index. Unsurprisingly, participants who reported meeting the recommended level of aerobic physical activity (at least 150 minutes/week of moderate-intensity activity, or at least 75 minutes/week of vigorous-intensity activity, or an equivalent combination) had lower risk of death than their peers who were insufficiently active. This applied to all-cause mortality and every specific cause of mortality assessed, including the big 3 of cardiovascular diseases, cancer, and chronic lower respiratory diseases. Associations held when adjusted for assorted covariates, including BMI and underlying medical conditions. Remarkably, the association between sufficient aerobic activity and all-cause mortality was nearly identical across their 3 BMI categories. Those with a normal BMI (<25), had a 30% lower risk of death, those with an overweight BMI (25 to <30) had a 29% lower risk, and those with an obese BMI (≥30) had a 27% lower risk.

What about diabetes? We cannot do better than the recent cohort study by Wei and colleagues, in which the investigators assessed the mortality implications of physical activity on nearly 50K adults with type 2 diabetes at baseline. For these individuals, achieving the recommended level of aerobic physical activity, compared to being inactive, was associated with a 32% lower risk of cardiovascular disease mortality and a 28% lower risk of non-cardiovascular disease mortality (adjusted for multiple covariates). Those who also conducted muscle-strengthening activity and vigorous-intensity aerobic activity achieved even better survival outcomes. In fact, compared to their inactive peers and fully adjusted for potential confounders, those who engaged in a single weekly episode of muscle-strengthening activity and 75-150 minutes/week of vigorous-intensity activity had a 70% lower risk of all-cause mortality. What matters most for our present purpose is buried in a supplementary table. In a subgroup analysis, individuals with T2D were stratified by baseline BMI into the typical categories of normal, overweight, and obesity, using identical definitions as those in the previous paragraph. Within each of these categories, those who engaged in sufficient aerobic physical activity had a lower mortality risk than their counterparts who were inactive. Among those with BMI-defined obesity, sufficient physical activity was associated with a 25% lower risk of all-cause mortality (fully adjusted hazard ratio of 0.75; 95% CI: 0.66, 0.87). ⁹

These 3 studies capture the downstream population-level outcomes of the individual-level biochemical mechanisms elucidated by Adams and colleagues in the journal’s present issue. For lifestyle medicine practitioners and their patients—and indeed for all of us—this is good news. It means that our metabolic health is determined in great measure by our behaviors (which we mostly control), regardless of our size and shape (which we mostly don’t). It means that the benefits of exerkines are available to all, if only we do what our body is designed to do: to move, lift, push, and pull. The upshot for clinical lifestyle medicine is that behavioral prescriptions should specify attainable goals, tackling the behavior itself rather than the potential phenotypic consequences of the behavior. ¹⁰ In light of the robust epidemiologic evidence linking physical activity to health independent of BMI, and acknowledging the damage of weight stigmatization, the time has come to reframe metabolic health as a behavioral phenomenon, where the number on the pedometer matters more than the number on the scale.