Most cases of type 2 diabetes (T2D) can be prevented by adopting a healthy lifestyle, highlighting that lifestyle modifications should be the primary defence against developing T2D. Although accumulating evidence suggests that exercise can be an efficacious therapy for T2D, especially in conjunction with pharmacological interventions, its long-term effectiveness remains controversial owing to significant adherence challenges. In this narrative review, we combine an evolutionary perspective with epidemiological and prospective interventional studies to examine the efficacy versus effectiveness of varying volumes of exercise prescriptions for treating T2D. Commonly prescribed and recommended volumes of moderate-intensity physical activity (150 min/week) have demonstrated low-to-moderate efficacy in improving glycaemic control, reflected by improvements in glycated haemoglobin levels. Higher exercise volumes have been shown to enhance efficacy. While exercise can be moderately efficacious under the optimal circumstances of short-term exercise interventions (≤1 year), there is little evidence of its long-term effectiveness, primarily due to poor adherence. To date, no study has demonstrated long-term adherence to exercise programmes in individuals with T2D (>1 year). From an evolutionary perspective, the finding that exercise interventions are often ineffective over time is unsurprising. Although often overlooked, humans never evolved to exercise. Exercise is a counter-instinctive behaviour that can be difficult to maintain, even in healthy populations and can be especially challenging for individuals who are unfit or have T2D morbidities. We conclude by presenting several considerations informed by evolutionary logic that may be useful for practitioners, policymakers and advocates of exercise as medicine to improve exercise adherence.

OBJECTIVES:Although humans used to be physically active hunter-gatherers and subsistence farmers, there has been a recent and ongoing global physical activity transition as billions of people adopt industrial lifestyles primarily in urban areas. In order to analyze how to quantify the magnitude of this physical activity transition in a natural experiment, we compared two different metrics of physical activity metabolism among intensive subsistence farmers in northern Rwanda (Burera District, Northern Province) and urban professionals in the country's main city, Kigali. METHODS:We used the doubly labeled water (DLW) method to measure body composition, daily energy expenditure, and estimate activity energy expenditure in 36 individuals (n = 19 rural, n = 17 urban). We then used two metrics to compare activity energetics between the groups: Physical Activity Level (PAL), the ratio of total to resting energy expenditure, and Activity Metabolic Quotients (AMQ), a size-normalized measure of the daily metabolic demand from physical activity. RESULTS:While PALs suggest that Rwandan farmers are 1.5 times more active than urban office workers on average (PAL: 2.41 vs. 1.56), AMQs indicate that the rural farmers actually spend 2.6 times more energy on physical activity than urban office workers (AMQ: 1.85 ± 0.09 vs. 0.72 ± 0.05, p < 0.0001). CONCLUSIONS:Metrics based on total daily metabolism such as PAL and TMQ captured some of the differences in physical activity metabolism between the farmers and office workers but severely underestimated the magnitude of the difference as illustrated by AMQ. We find that rural Rwandan farmers have some of the highest physical activity metabolic rates ever measured in humans, emphasizing the magnitude of the physical activity transition and suggesting that subsistence farming can demand much higher energy expenditures compared not just to industrial lifestyles but also to hunting and gathering.

Back endurance is a strong predictor of back pain, but the mechanisms underlying this relationship are not clear. Fatigue reduces muscles' force-generating capacity, so greater fatigability may increase lumbar motion and loading and trunk muscle co-contraction. Using a novel pack to modify inertia, we tested the effect of back fatigue and increased trunk inertia on lumbar kinematics, kinetics and muscle activity during walking. Lumbar kinematic and kinetic amplitudes and maximum muscle activity were measured per stride across four conditions: pre- and post-fatigue, with and without increased trunk inertia. The pack caused increases in maximum lumbar erector spinae (ES) activity by 3.19 times the average value calculated during the pre-fatigue no-pack trial (P<0.001), amplitude of lumbar flexion-extension moment by 0.0189 N m (kg g m)-1 (P<0.001), lumbar lateral bending moment by 0.0028 N m (kg g m)-1 (P=0.019) and lumbar axial rotation moment by 0.0203 N m (kg g m)-1 (P<0.001), and decreases in the amplitude of roll angle by 1.31 deg and yaw angle by 6.65 deg (both P<0.001). Back endurance is positively associated with change in maximum lumbar ES activity (r=0.69, P=0.013) and negatively associated with change in maximum rectus abdominus (RA) activity (r=-0.72, P=0.008) and lumbar flexion-extension moment amplitude (r=-0.62, P=0.031). Overall, individuals with less back endurance had increased maximum RA activity and sagittal kinetics post-fatigue whereas individuals with higher back endurance showed the opposite response. Increased RA activity with less back endurance may be a protective mechanism for stabilizing the trunk in response to increased sagittal lumbar loading due to fatigue.

Accurately estimating kinetic metrics, such as braking and propulsion forces, in real-world running environments enhances our understanding of performance, fatigue, and injury. Wearable inertial measurement units (IMUs) offer a potential solution to estimate kinetic metrics outside the lab when combined with machine learning. However, current IMU-based kinetic estimation models are trained and evaluated within a single environment, often on lab treadmills. The transferability of these treadmill-trained models during overground running in and out of the lab is underexplored, and the individualization and validation of such models remain a challenge. Toward bridging this gap, we trained a generalized model on treadmill data of 15 recreational runners and evaluated braking and propulsion force estimates during overground running in and out of the lab. We explored fine-tuning with individual data from lab-based overground running to quantify model performance improvements with individualization. The generalized and fine-tuned models were extrapolated to outdoor running for a subset of five participants, and estimates were compared to lab-based overground measurements. Evaluating the generalized model with a leave-one-out cross validation yielded overground braking and propulsion force root mean squared error of 4.3 ± 1.1 % bodyweight (%BW). Fine-tuning this model with eight strides reduced error to 2.6 ± 0.5 %BW. Outdoor force predictions from the fine-tuned model better aligned with expected linear trends between braking/propulsion impulses and speed than the generalized model. These results provide insights into the accuracy and applicability of IMU data-driven models for braking and propulsion estimation during overground running, facilitating the development of practical, individualized biomechanical analysis tools for real-world use.

Optical motion capture (OMC) is considered the best available method for measuring spine kinematics, yet inertial measurement units (IMU) have the potential to collect data outside the laboratory. When combined with musculoskeletal modeling, IMU technology may be used to estimate spinal loads in real-world settings. To date, IMUs have not been validated for estimates of spinal movement and loading during both walking and running. Using OpenSim Thoracolumbar Spine and Ribcage models, we compare IMU and OMC estimates of lumbosacral (L5/S1) and thoracolumbar (T12/L1) joint angles, moments, and reaction forces during gait across six speeds for five participants. For comparisons, time series are ensemble averaged over strides. Comparisons between IMU and OMC ensemble averages have low normalized root mean squared errors (< 0.3 for 81% of comparisons) and high, positive cross-correlations (> 0.5 for 91% of comparisons), suggesting signals are similar in magnitude and trend. As expected, joint moments and reaction forces are higher during running than walking for IMU and OMC. Relative to OMC, IMU overestimates joint moments and underestimates joint reaction forces by 20.9% and 15.7%, respectively. The results suggest using a combination of IMU technology and musculoskeletal modeling is a valid means for estimating spinal movement and loading.

During vigorous physical activity, contracting muscles secrete a variety of immunomodulatory and metabolic factors called myokines that perform a variety of functions. Foremost among these is interleukin 6 (IL-6), which increases fatty acid mobilization and stimulates anti-inflammatory cytokine release. Despite being well characterized in vigorous exercise contexts, whether IL-6 is secreted during moderate-intensity activities such as walking is unclear. This is especially pertinent as regular walking is one of the oldest and most common forms of physical activity and comes with a variety of health benefits, which may be coordinated in part by IL-6 signaling. To test the hypothesis that IL-6 release occurs during evolutionarily normal physical activity contexts like long distance walking, we performed a dose-response experiment to test the effect of walking duration on IL-6 secretion. Thirteen participants completed four moderate-intensity walking trials (55% HRmax) of varying durations (30 min, 1 h, 2 h, and 3 h) in a randomized order with intervening washout periods of at least 1 week. Using a linear mixed effects model, we found that IL-6 levels modestly increased during only the 2 h and 3 h walking trials. These results suggest that small frequent increases in IL-6 signaling may be an important mechanism underlying the health benefits of regular walking. Furthermore, this finding raises the possibility that IL-6 secretion is an adaptation to fuel physical activity, especially during periods of negative energy balance.

All organisms use limited energy to grow, survive, and reproduce, necessitating energy allocation tradeoffs, but there is debate over how selection impacted metabolic budgets and tradeoffs in primates, including humans. Here, we develop a method to compare metabolic rates as quotients of observed relative to expected values for mammals corrected for size, body composition, environmental temperature, and phylogenetic relatedness. Contrary to previous analyses, these quotients reveal that nonhuman primates have total metabolic rates expected for similar-sized mammals in similar environments. In addition, data from several small-scale societies show that humans evolved exceptionally high resting, activity, and total metabolic rates apparently by overcoming tradeoffs between resting and active energy expenditures that constrain other primates. Enhanced metabolic rates help humans fuel expanded brains, faster reproductive rates, extended longevity, and high percentage of body fat.

Shoes affect the evolved biomechanics of the foot, potentially affecting running kinematics and kinetics that can in turn influence injury and performance. An important feature of conventional running shoes is heel height, whose effects on foot and ankle biomechanics remain understudied. Here, we investigate the effects of 6-26 mm increases in heel height on ankle dynamics in 8 rearfoot strike runners who ran barefoot and in minimal shoes with added heels. We predicted higher heels would lead to greater frontal plane ankle torques due to the increased vertical moment arm of the mediolateral ground reaction force. Surprisingly, the torque increased in minimal shoes with no heel elevation, but then decreased with further increases in heel height due to changes in foot posture. We also found that increasing heel height caused a large increase in the ankle plantarflexion velocity at heel strike, which we explain using a passive collision model. Our results highlight how running in minimal shoes may be significantly different from barefoot running due to complex interactions between proprioception and biomechanics that also permit runners to compensate for modifications to shoe design, more in the frontal than sagittal planes.

Running injuries are prevalent, but their exact mechanisms remain unknown largely due to limited real-world biomechanical analysis. Reducing overstriding, the horizontal distance that the foot lands ahead of the body, may be relevant to reducing injury risk. Here, we leverage the geometric relationship between overstriding and lower extremity sagittal segment angles to demonstrate that wearable inertial measurement units (IMUs) can predict overstriding during treadmill and overground running in the laboratory. Ten recreational runners matched their strides to a metronome to systematically vary overstriding during constant-speed treadmill running and showed similar overstriding variation during comfortable-speed overground running. Linear mixed models were used to analyze repeated measures of overstriding and sagittal segment angles measured with motion capture and IMUs. Sagittal segment angles measured with IMUs explained 95% and 98% of the variance in overstriding during treadmill and overground running, respectively. We also found that sagittal segment angles measured with IMUs correlated with peak braking force and explained 88% and 80% of the variance during treadmill and overground running, respectively. This study highlights the potential for IMUs to provide insights into landing and loading patterns over time in real-world running environments, and motivates future research on feedback to modify form and prevent injury.

Chronic medical conditions caused by the inadequate adaptation of the body to modern lifestyles, such as physical inactivity and unhealthy diets, are on the rise. This study assessed whether a comprehensive lifestyle intervention, including high volumes of supervised exercise, could improve health outcomes. Eight volunteers with lifestyle-related diseases received a 6-month lifestyle intervention consisting of 8000-10 000 steps/day, 6 moderate-intensity endurance and 3 resistance training sessions per week, a 5-week long hike, and dietary advice. This was followed by 7 months of limited remote supervision, ending 13 months from baseline. The participants (3 females, 5 males; mean age 42.9 years) had conditions including type 2 diabetes (T2D), depression/stress, and metabolic syndrome (MS). After 6 months, body weight decreased significantly by 23 kg (95% CI; -33.7 to -12.2), with a minor non-significant decrease in lean body mass of 1.96 kg (95% CI; -4.34 to 0.27). Maximal oxygen consumption (VO2max) increased by 18.5 mL/O2/kg/min. (95% CI; 13.8-23.1) and systolic and diastolic blood pressures decreased by 33 (95% CI; -39 to -26) and 18 mmHg (95% CI; -23 to -14), respectively. Three of the 4 participants with T2D had normalized glycated hemoglobin (HbA1c) levels, and all showed improved 2-h oral glucose tolerance (OGTT) without pharmacological treatment. Participants with T2D continued to lower HbA1c during the 7-month follow-up period. This 6-month lifestyle intervention restored metabolic health and improved cardiovascular health in 8 participants with lifestyle-related diseases while reducing the need for pharmacological treatments. These findings suggest that comprehensive lifestyle changes can reverse several medical conditions caused by evolutionary mismatch.

BACKGROUND:Although human diets varied considerably before the spread of agriculture, public perceptions of preagricultural diets have been strongly influenced by the Paleo Diet, which prescribes percentage calorie ranges of 19-35% protein, 22-40% carbohydrate, and 28-47% fat, and prohibits foods with added sugar, dairy, grains, most starchy tubers, and legumes. However, the empirical basis for Paleolithic nutrition remains unclear, with some of its assumptions challenged by the archaeological record and theoretical first principles. OBJECTIVES:We assessed the variation in diets among tropical hunter-gatherers, including the effect of collection methods on implied macronutrient percentages. METHODS:We analyzed data on animal food, plant food, and honey consumption by weight and kcal from 15 high-quality published ethnographic studies representing 11 recent tropical hunter-gatherer groups. We used Bayesian analyses to perform inference and included data collection methods and environmental variables as predictors in our models. RESULTS:Our analyses reveal high levels of variation in animal versus plant foods consumed and in corresponding percentages of protein, fat, and carbohydrates. In addition, studies that weighed food items consumed in and out of camp and across seasons and years reported higher consumption of animal foods, which varied with annual mean temperature. CONCLUSIONS:The ethnographic evidence from tropical foragers refutes the concept of circumscribed macronutrient ranges modeling preagricultural diets.

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

We examined the effects of vertical load placement on the metabolic cost of walking. Twelve healthy participants walked on a treadmill with 13.8 and 23.4 kg loads in both high and low vertical positions. Metabolic rate was measured using respirometry. While load position had no effect on the net metabolic rate for the 13.8 kg load, the net metabolic rate with the 23.4 kg load was significantly reduced by 4.3% in the high vertical load position compared to the low vertical load position. Loads carried higher on the trunk were also associated with increased forward trunk lean that reduced the load gravitational moment arm in the sagittal plane suggesting that reduction of fore-aft upper body torques is an energy-saving mechanism during loaded walking. Practitioner Summary: Load placement within a backpack affects the biomechanics of load carriage. We experimentally tested the metabolic cost of high and low load placement during walking and found the high position to be less costly with large loads. Loading high may be the optimal technique for carrying heavy backpacks.

Globally, we are witnessing the rise of complex, non-communicable diseases (NCDs) related to changes in our daily environments. Obesity, asthma, cardiovascular disease, and type 2 diabetes are part of a long list of "lifestyle" diseases that were rare throughout human history but are now common. A key idea from anthropology and evolutionary biology-the evolutionary mismatch hypothesis-seeks to explain this phenomenon. It posits that humans evolved in environments that radically differ from the ones experienced by most people today, and thus traits that were advantageous in past environments may now be "mismatched" and disease-causing. This hypothesis is, at its core, a genetic one: it predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions and have differential health effects in ancestral versus modern environments. Here, we discuss how this concept could be leveraged to uncover the genetic architecture of NCDs in a principled way. Specifically, we advocate for partnering with small-scale, subsistence-level groups that are currently transitioning from environments that are arguably more "matched" with their recent evolutionary history to those that are more "mismatched". These populations provide diverse genetic backgrounds as well as the needed levels and types of environmental variation necessary for mapping GxE interactions in an explicit mismatch framework. Such work would make important contributions to our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and sociocultural contexts.

There is debate and confusion over how to evaluate the biomechanical effects of running shoe design. Here, we use an evolutionary perspective to analyze how key design features of running shoes alter the evolved biomechanics of the foot, creating a range of tradeoffs in force production and transmission that may affect performance and vulnerability to injury.

The prevalence of obesity has reached pandemic proportions, and now approximately 25% of adults in Westernized countries have obesity. Recognized as a major health concern, obesity is associated with multiple comorbidities, particularly cardiometabolic disorders. In this Review, we present obesity as an evolutionarily novel condition, summarize the epidemiological evidence on its detrimental cardiometabolic consequences and discuss the major mechanisms involved in the association between obesity and the risk of cardiometabolic diseases. We also examine the role of potential moderators of this association, with evidence for and against the so-called 'metabolically healthy obesity phenotype', the 'fatness but fitness' paradox or the 'obesity paradox'. Although maintenance of optimal cardiometabolic status should be a primary goal in individuals with obesity, losing body weight and, particularly, excess visceral adiposity seems to be necessary to minimize the risk of cardiometabolic diseases.