Molecular Transducers of Physical Activity Consortium (MoTrPAC): Human Studies Design and Protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. While there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multi-center study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a pre-clinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 weeks of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 weeks. The adult component also includes recruitment of highly active endurance trained or resistance trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.

Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease.

BACKGROUND: Despite the benefits of exercise, many individuals are unable or unwilling to adopt an exercise intervention. PURPOSE: The purpose of this analysis was to identify putative genetic variants associated with dropout from exercise training interventions among individuals in the STRRIDE trials. METHODS: We used a genome-wide association study approach to identify genetic variants in 603 participants initiating a supervised exercise intervention. Exercise intervention dropout occurred when a subject withdrew from further participation in the study or was otherwise lost to follow-up. RESULTS: Exercise intervention dropout was associated with a cluster of single-nucleotide polymorphisms with the top candidate being rs722069 (T/C, risk allele = C) (unadjusted p = 2.2 × 10-7, odds ratio = 2.23) contained within a linkage disequilibrium block on chromosome 16. In Genotype-Tissue Expression, rs722069 is an expression quantitative trait locus of the EARS2, COG7, and DCTN5 genes in skeletal muscle tissue. In subsets of the STRRIDE genetic cohort with available muscle gene expression (n = 37) and metabolic data (n = 82), at baseline the C allele was associated with lesser muscle expression of EARS2 (p < .002) and COG7 (p = .074) as well as lesser muscle concentrations of C2- and C3-acylcarnitines (p = .026). CONCLUSIONS: Our observations imply that exercise intervention dropout is genetically moderated through alterations in gene expression and metabolic pathways in skeletal muscle. Individual genetic traits may allow the development of a biomarker-based approach for identifying individuals who may benefit from more intensive counseling and other interventions to optimize exercise intervention adoption. CLINICAL TRIAL INFORMATION: STRRIDE I = NCT00200993; STRRIDE AT/RT = NCT00275145; STRRIDE-PD = NCT00962962.

Regular participation in exercise can provide a myriad of health benefits. Although individuals recognize these benefits, many are unable or unwilling to adopt an exercise intervention once initiated. The purpose of this analysis was to identify genetic variants associated with dropout from an exercise training intervention. We found exercise intervention dropout to be genetically moderated through changes in gene expression and metabolic pathways in muscle. Thus, individual genetic traits may allow for the development of a biomarker-based targeted approach for identifying individuals who may benefit from more intensive counseling and interventions to optimize the adoption of an exercise intervention program.

Effect of Remotely Supervised Weight Loss and Exercise Training Versus Lifestyle Counseling on Cardiovascular Risk and Clinical Outcomes in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient-reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. METHODS: Twenty older (60-80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate-to-vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check-ins. The primary outcome was a composite metabolic syndrome z-score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein-cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient-reported outcomes. RESULTS: Both groups improved MSSc (absolute change -1.67 ± 0.64 in SWET; -1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between-group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score-28 C-reactive protein, and patient-reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between-group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component-specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score-28 C-reactive protein. CONCLUSION: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient-reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at-risk RA population.

Effects of exercise amount and intensity versus a combined exercise and lifestyle intervention on metabolic syndrome in adults with prediabetes: a STRRIDE-PD randomized trial.

The purpose of this secondary analysis was to determine what portion of the effects of a Diabetes Prevention Program-like intervention on metabolic syndrome (MetS) could be achieved with exercise alone, as well as to determine the relative importance of exercise intensity and amount to the total exercise effect on MetS. Sedentary, overweight adults with prediabetes were randomly assigned to one of four 6-month interventions: 1) low-amount/moderate-intensity (10 kcal/kg/week at 50% peak V˙O2); 2) high-amount/moderate-intensity (16 kcal/kg/week at 50% peak V˙O2); 3) high-amount/vigorous-intensity (16 kcal/kg/week at 75% peak V˙O2); or 4) diet (7% weight loss) plus low-amount/moderate-intensity (10 kcal/kg/week at 50% peak V˙O2). The primary outcome of this secondary analysis was change in the MetS z-score. A total of 130 participants had complete data for all five Adult Treatment Panel (ATP) III MetS criteria. The diet-and-exercise group statistically outperformed the MetS z-score and the ATP III score compared to the exercise alone group. Aerobic exercise alone achieved 24%-50% of the total effect of the combined diet-and-exercise intervention on the MetS score. Low-amount moderate-intensity exercise quantitatively performed equal to or better than the interventions of high-amount moderate-intensity or high-amount vigorous-intensity exercise in improving the MetS score. The combined diet-and-exercise intervention remains more efficacious in improving the MetS z-score. However, all three exercise interventions alone showed improvements in the MetS z-score, suggesting that a modest amount of moderate-intensity exercise is all that is required to achieve approximately half the effect of a diet-and-exercise intervention on the MetS. Clinical Trial Registration: clinicaltrials.gov, identifier NCT00962962.

Remotely Supervised Weight Loss and Exercise Training to Improve Rheumatoid Arthritis Cardiovascular Risk: Rationale and Design of the Supervised Weight Loss Plus Exercise Training-Rheumatoid Arthritis Trial.

Patients with rheumatoid arthritis (RA) remain at an increased risk for cardiovascular disease (CVD) and mortality. RA CVD results from a combination of traditional risk factors and RA-related systemic inflammation. One hypothetical means of improving overall RA CVD risk is through reduction of excess body weight and increased physical activity. Together, weight loss and physical activity can improve traditional cardiometabolic health through fat mass loss, while also improving skeletal muscle health. Additionally, disease-related CVD risk may improve as both fat mass loss and exercise reduce systemic inflammation. To explore this hypothesis, 26 older persons with RA and overweight/obesity will be randomized to 16 weeks of a usual care control arm or to a remotely Supervised Weight Loss Plus Exercise Training (SWET) program. A caloric restriction diet (targeting 7% weight loss) will occur via a dietitian-led intervention, with weekly weigh-ins and group support sessions. Exercise training will consist of both aerobic training (150 minutes/week moderate-to-vigorous exercise) and resistance training (twice weekly). The SWET remote program will be delivered via a combination of video conference, the study YouTube channel, and study mobile applications. The primary cardiometabolic outcome is the metabolic syndrome Z score, calculated from blood pressure, waist circumference, high-density lipoprotein cholesterol, triglycerides, and glucose. RA-specific CVD risk will be assessed with measures of systemic inflammation, disease activity, patient-reported outcomes, and immune cell function. The SWET-RA trial will be the first to assess whether a remotely supervised, combined lifestyle intervention improves cardiometabolic health in an at-risk population of older individuals with RA and overweight/obesity.

Branched-Chain Amino Acid Catabolism and Cardiopulmonary Function Following Acute Maximal Exercise Testing in Adolescents.

Background: To provide energy for cardiopulmonary function and maintenance of blood glucose, acute aerobic exercise induces lipolysis, fatty acid oxidation (FAO), glycolysis, and glycogenolysis/gluconeogenesis. These adaptations are mediated by increases in cortisol, growth hormone (GH), and catecholamines and facilitated by a decline in insulin. Branched-chain amino acids (BCAA) also undergo catabolism during intense exercise. Here, we investigated the relationship between BCAA catabolism and metrics of cardiopulmonary function in healthy, well-developed, mature adolescent athletes undergoing an acute bout of maximal aerobic exercise. Hypothesis: We hypothesized: (a) acute maximal exercise in adolescents induces lipolysis, FAO, and BCAA catabolism associated with increases in GH and cortisol and a reduction in insulin; (b) increases in GH are associated with increases in ghrelin; and (c) metrics of cardiopulmonary function (aVO2, rVO2, aVO2/HRmax) following maximal exercise correlate with increases in GH secretion, FAO, and BCAA catabolism. Methods: Blood samples before and after maximal cardiopulmonary exercise in 11 adolescent athletes were analyzed by tandem-mass spectrometry. Paired, two-tailed student's t-tests identified significant changes following exercise. Linear regression determined if pre-exercise metabolite levels, or changes in metabolite levels, were associated with aVO2, rVO2, and aVO2/HRmax. Sex and school of origin were included as covariates in all regression analyses. Results: Following exercise there were increases in GH and cortisol, and decreases in ghrelin, but no changes in glucose or insulin concentrations. Suggesting increased lipolysis and FAO, the levels of glycerol, ketones, ß-hydroxybutyrate, and acetylcarnitine concentrations increased. Pyruvate, lactate, alanine, and glutamate concentrations also increased. Plasma concentrations of valine (a BCAA) declined (p = 0.002) while valine degradation byproducts increased in association with decreases in urea cycle amino acids arginine and ornithine. Metrics of cardiopulmonary function were associated with increases in propionylcarnitine (C3, p = 0.013) and Ci4-DC/C4-DC (p < 0.01), byproducts of BCAA catabolism. Conclusions: Induction of lipolysis, FAO, gluconeogenesis, and glycogenolysis provides critical substrates for cardiopulmonary function during exercise. However, none of those pathways were significantly associated with metrics of cardiopulmonary function. The associations between rVO2, and aVO2/HRmax and C3 and Ci4-DC/C4-DC suggest that the cardiopulmonary response to maximal exercise in adolescents is linked to BCAA utilization and catabolism.

A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors.

INTRODUCTION: To assess the feasibility of a home-based aerobic exercise and nutrition counseling intervention and effect on cardiorespiratory fitness, cardiovascular disease risk profile, and immune response in obese endometrial cancer survivors. METHODS: A longitudinal pilot study assessed a 12-week home-based aerobic exercise and nutrition counseling intervention in obese endometrial cancer survivors. The primary outcome was feasibility defined as 80% adherence to weekly walking sessions calculated among individuals that completed the intervention. Secondary outcomes comprised pre- and post-intervention differences in cardiorespiratory fitness, cardiovascular risk factors, and T-cell function. Descriptive statistics summarized data. Wilcoxon sign tests identified differences between and pre and post-intervention variables. RESULTS: Nineteen women with stage 1 endometrial cancer consented; 9 withdrew and one was a screen failure. Median adherence to weekly walking sessions was 83.3%. Body composition was significantly altered with a reduction in median fat mass from 52.5 kg to 46.9 kg (p=0.04), and BMI from 37.5 kg/m2 to 36.2 kg/m2 (p = 0.004). There was no significant difference in cardiorespiratory fitness or cardiovascular parameters. The percentage of CD4+ and CD8+ T-cells producing IFNγ towards MAGE-A4 significantly increased from and 5.9% to 7.2% (p=0.043) and 13.9% to 14.8% (p=0.046), respectively. There were 3 related adverse events: hip pain, back sprain, and abdominal pain. DISCUSSION: Our home-based exercise and nutrition counseling program was feasible based on 80% adherence to walking sessions and favored altered body composition. However, the discontinuation rate was high and further research is needed to overcome barriers to implementation. Improvement in cardiovascular parameters will most likely require longer and more intensive programs.

Cardiopulmonary Exercise Testing in the Coronavirus Disease - 2019 Era: Safety and Protocol Considerations.

ABSTRACT: Cardiopulmonary exercise testing (CPX) is a valuable tool in both clinical practice and research settings. Therefore, it is advantageous for human performance laboratories to continue operating during the coronavirus disease 2019 (COVID-19) pandemic. All institutions should adhere to general COVID-19 guidelines provided by the Centers for Disease Control. Because of the testing environment, CPX laboratories must consider additional precautionary safety measures. This article provides recommendations for modifying the CPX protocol to ensure safety for all stakeholders during the pandemic. These modifications are universal across all populations, types of institutions and testing modalities. Preliminary measures include careful review of federal, local, and institutional mandates. The description outlines how to evaluate a testing environment and alter workflow. Guidelines are provided on what specific personal protective equipment should be acquired; as well as necessary actions before, during, and after the CPX test. These precautions will limit the possibility of both clients and staff from contracting or spreading the disease while maintaining testing volume in the laboratory.

The tropical Pacific Oceanscape: Current issues, solutions and future possibilities.

Marine ecosystems across the world's largest ocean - the Pacific Ocean - are being increasingly affected by stressors such as pollution, overfishing, ocean acidification, coastal development and warming events coupled with rising sea levels and increasing frequency of extreme weather. These anthropogenic-driven stressors, which operate cumulatively at varying spatial and temporal scales, are leading to ongoing and pervasive degradation of many marine ecosystems in the Pacific Island region. The effects of global warming and ocean acidification threaten much of the region and impact on the socio-cultural, environmental, economic and human health components of many Pacific Island nations. Simultaneously, resilience to climate change is being reduced as systems are overburdened by other stressors, such as marine and land-based pollution and unsustainable fishing. Consequently, it is important to understand the vulnerability of this region to future environmental scenarios and determine to what extent management actions can help protect, and rebuild ecosystem resilience and maintain ecosystem service provision. This Special Issue of papers explores many of these pressures through case studies across the Pacific Island region, and the impacts of individual and cumulative pressures on the condition, resilience and survival of ecosystems and the communities that depend on them. The papers represent original work from across the tropical Pacific oceanscape, an area that includes 22 Pacific Island countries and territories plus Hawaii and the Philippines. The 39 papers within provide insights on anthropogenic pressures and habitat responses at local, national, and regional scales. The themes range from coastal water quality and human health, assessment of status and trends for marine habitats (e.g. seagrass and coral reefs), and the interaction of local pressures (pollution, overfishing) with increasing temperatures and climate variability. Studies within the Special Issue highlight how local actions, monitoring, tourism values, management, policy and incentives can encourage adaptation to anthropogenic impacts. Conclusions identify possible solutions to support sustainable and harmonious environment and social systems in the unique Pacific Island oceanscape.

Synergies between local and climate-driven impacts on coral reefs in the Tropical Pacific: A review of issues and adaptation opportunities.

Coral reefs in the tropical Pacific region are exposed to a range of anthropogenic local pressures. Climate change is exacerbating local impacts, causing unprecedented declines in coral reef habitats and bringing negative socio-economic consequences to Pacific communities who depend heavily on coral reefs for food, income and livelihoods. Continued increases in greenhouse gas emissions will drive future climate change, which will accelerate coral reef degradation. Traditional systems of resource governance in Pacific island nations provide a foundation to address local pressures and build reef resilience to climate change. Management and adaptation options should build on the regional diversity of governance systems and traditional knowledge to support community-based initiatives and cross-sectoral cooperation to address local pressures and minimize climate change impacts. Such an inclusive approach will offer enhanced opportunities to develop and implement transformative adaptation solutions, particularly in remote and regional areas where centralized management does not extend.

Community Marine Monitoring Toolkit: A tool developed in the Pacific to inform community-based marine resource management.

In the Pacific region, community engagement, participation and empowerment are key to effective and sustainable marine resource management at the local level. With the prevalence of a local marine tenure systems and the widespread decline of coastal resources, communities need to be part of the solution to facilitate recovery. A novel marine monitoring toolkit was developed in Vanuatu with the participation of community resource monitors to inform local management actions. The Toolkit includes simplified versions of established monitoring methods for marine habitats and resources to achieve a balance between robust science and methods appropriate for communities. Key to its success is that it was developed in response to community needs using a participatory approach and implemented through a series of training workshops with local environmental leaders. Of particular note, the Toolkit includes a standardised process for communities to use monitoring results instantly, without the need for complex data analyses or external support. Using the Toolkit, communities are able to adapt their traditional management to address immediate and medium-term issues in their local marine environment. The observed benefits of the Toolkit include increased local awareness through community-led environmental outreach, increased ownership of and motivation for local monitoring and management, implementation of local management actions, expansion of traditional marine managed areas, and new local ecotourism initiatives to generate revenue to support environmental stewardship.

Community-based adaptation to climate change in villages of Western Province, Solomon Islands.

People, local cultures and the environments they live in are complex and dynamic social-ecological systems that have evolved together over time and are continually affected by a myriad of factors, including climate and global changes. Escalating climate and global changes present an imminent threat to Pacific communities, particularly for food security, livelihoods, health and safety, cultural identity and biodiversity conservation. A participatory community-based climate change adaptation planning process was used to engage with communities on Rendova Island in Western Province, Solomon Islands to identify local adaptation priorities. The methodology recognized that local community members are the managers of the resources they use daily, have direct knowledge of the status of key local resources and have direct influence over ongoing resource governance. The study focused on two objectives: (1) identifying community priorities and documenting them in adaptation plans intended for local implementation, and (2) evaluating whether community adaptation priorities addressed key vulnerabilities identified independently using a semi-quantitative vulnerability assessment. The adaptation priorities identified by the communities encompassed: governance, leadership and planning; farming and livestock; sustainable livelihoods; natural resource management; and youth capacity building. The community adaptation priorities were found to address the key climate change vulnerabilities identified in the semi-quantitative assessment and also addressed additional drivers of social vulnerability and adaptive capacity. This finding reiterates the importance of fully inclusive and participatory vulnerability assessments and community-identification of adaptation priorities coupled with scientific climate projections to comprehensively assess the complexity of social-ecological systems. The climate change adaptation priorities have informed ongoing local actions and are intended to be used by communities, government and NGOs to focus local effort, funding and project development. A review of the suitability of the adaptation priorities by similar villages on neighbouring islands would determine the utility of scaling-up and applying these adaptations to other rural communities in the Solomon Islands, and possibly more widely in other Pacific communities.

Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease.

INTRODUCTION: Low potassium intake can affect cardiovascular disease (CVD) risk and cardiometabolic risk factors. OBJECTIVE: We hypothesize that potassium chloride (KCl) supplementation can improve cardiovascular risk metabolomic profile. METHODS: In this secondary analysis of a pilot randomized clinical trial (RCT) of 26 participants with prediabetes randomized to KCl or placebo, we performed targeted mass-spectrometry-based metabolomic profiling on baseline and 12-week (end-of-study) plasma samples. Principal component analysis (PCA) was used to reduce the many correlated metabolites into fewer, independent factors that retain most of the information in the original data. RESULTS: Those taking KCl had significant reductions (corresponding to lower cardiovascular risk) in the branched-chain amino acids (BCAA) factor (P = 0.004) and in valine levels (P = 0.02); and non-significant reductions in short-chain acylcarnitines (SCA) factor (P = 0.11). CONCLUSIONS: KCl supplementation may improve circulating BCAA levels, which may reflect improvements in overall cardiometabolic risk profile. CLINICAL TRIALS REGISTRY: Clinicaltrials.gov identifier: NCT02236598; https://clinicaltrials.gov/ct2/show/NCT02236598.

Short-Term Changes in Cardiorespiratory Fitness in Response to Exercise Training and the Association with Long-Term Cardiorespiratory Fitness Decline: The STRRIDE Reunion Study.

Background Substantial heterogeneity exists in the cardiorespiratory fitness (CRF) change in response to exercise training, and its long-term prognostic implication is not well understood. We evaluated the association between the short-term supervised training-related changes in CRF and CRF levels 10 years later. Methods and Results STRRIDE (Studies of a Targeted Risk Reduction Intervention Through Defined Exercise) trial participants who were originally randomized to exercise training for 8 months and participated in the 10-year follow-up visit were included. CRF levels were measured at baseline, after training (8 months), and at 10-year follow-up as peak oxygen uptake (vo2, mL/kg per min) using the maximal treadmill test. Participants were stratified into low, moderate, and high CRF response groups according to the training regimen-specific tertiles of CRF change. The study included 80 participants (age: 52 years; 35% female). At 10-year follow-up, the high-response CRF group had the least decline in CRF compared with the moderate- and low-response CRF groups (-0.35 versus -2.20 and -4.25 mL/kg per minute, respectively; P=0.02). This result was largely related to the differential age-related changes in peak oxygen pulse across the 3 groups (0.58, -0.23, and -0.86 mL/beat, respectively; P=0.03) with no difference in the peak heart rate change. In adjusted linear regression analysis, high response was significantly associated with greater CRF at follow-up independent of other baseline characteristics (high versus low [reference] CRF response: standard ß=0.25; P=0.004). Conclusions Greater CRF improvement in response to short-term training is associated with higher CRF levels 10 years later. Lack of CRF improvements in response to short-term training may identify individuals at risk for exaggerated CRF decline with aging.

Effects of Exercise Training With and Without Ranolazine on Peak Oxygen Consumption, Daily Physical Activity, and Quality of Life in Patients With Chronic Stable Angina Pectoris.

Ranolazine reduces angina frequency and increases exercise capacity. We hypothesized that exercise training with ranolazine would allow subjects to train at greater intensities, resulting in greater improvements in exercise capacity, physical activity, and health-related quality of life (HRQOL). In a pilot study, subjects with chronic stable angina pectoris were randomized to ranolazine (n = 13) or placebo (n = 16). After a 2-week drug titration period, subjects participated in a 12-week exercise program. Peak VO2, physical activity (via accelerometer), and HRQOL were assessed before and after training. After exercise training, peak VO2increased twice as much with ranolazine (2.1 ± 3.4 ml/kg/min) as with placebo (0.9 ± 1.5) (both p <0.05). After exercise training, both groups significantly improved HRQOL score (p <0.05); however, the improvement with ranolazine (19 ± 21) was almost 50% greater than with placebo (13 ± 18). There was a significant decrease in maximal heart rate after training with ranolazine but not with placebo (group difference, p = 0.04). Oxygen pulse (peak VO2/peak HR) increased in both groups after training; but, the increase was 4 times greater with ranolazine - resulting in a significant difference between groups (p = 0.044). In conclusion, patients with angina, the addition of ranolazine to an exercise program may improve aerobic fitness, physical activity, and HRQOL beyond the results of an exercise training program alone. Exercise training with ranolazine led to significantly greater increases in oxygen pulse, which is significantly correlated with stroke volume and is an independent predictor of mortality.

Ten-Year Legacy Effects of Three Eight-Month Exercise Training Programs on Cardiometabolic Health Parameters.

Background: STRRIDE (Studies Targeting Risk Reduction Interventions through Defined Exercise) was an eight-month exercise study conducted from 1998-2003. Subjects were randomized to control or one of three exercise groups differing in intensity and amount. To determine if there were legacy effects, we invited 161 individuals who completed the intervention phase to return for a 10-year Reunion study. Methods: Subjects completed medical history and physical activity questionnaires. Height, body weight, blood pressure, waist circumference, and peak VO2 were measured. Fasting blood samples were analyzed for glucose, insulin and lipids. Of 161 original subjects, 153 were within 10 years of STRRIDE completion. Of these, 28 were lost to follow-up and 21 declined to participate in the Reunion study. Overall, 104 subjects (83% eligible) participated. Change over time was computed as the 10-year Reunion value minus the pre-intervention value. Significant within group changes were calculated using two-tailed t-tests. ANCOVA determined differences among groups with pre-intervention values as covariates. Bonferroni corrections were applied to account for multiple comparisons. Results: Ten years after completing STRRIDE, there were a number of group-specific health and fitness legacy effects. Original participation in either the moderate intensity exercise or control group resulted in a 10.5% decrease in peak VO2 over the ensuing 10 years. Conversely, both vigorous intensity groups experienced only a 4.7% decrement in cardiorespiratory fitness over that time period. As compared to controls, all three exercise groups experienced smaller increases in waist circumference. Those who participated in moderate intensity exercise experienced the greatest 10-year reduction in fasting insulin. Compared to all other groups, the moderate intensity subjects had greater reductions in mean arterial pressure at the Reunion timepoint. Summary: Ten years after completing a randomized eight-month exercise training intervention, previously sedentary individuals exhibited group-specific differences consistent with an intervention-based legacy effect on cardiorespiratory fitness and cardiometabolic parameters. These findings highlight the critical need to better understand the sustained legacy health effects of exercise training interventions.

Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial.

Background: Low potassium has been identified both as a risk factor for type 2 diabetes and as a mediator of the racial disparity in diabetes risk. Low potassium could be a potentially modifiable risk factor, particularly for African Americans.Objective: We sought to determine the effects of potassium chloride (KCl) supplements, at a commonly prescribed dose, on measures of potassium and glucose metabolism.Design: Among African-American adults with prediabetes, we conducted a double-blinded pilot randomized controlled trial that compared the effects of 40 mEq K/d as KCl supplements with a matching placebo, taken for 3 mo, on measures of potassium and glucose metabolism, with measures collected from frequently sampled oral-glucose-tolerance tests (OGTTs).Results: Twenty-seven of 29 recruited participants completed the trial. Participants had high adherence to the study medication (92% by pill count). Participants in both groups gained weight, with an overall mean ± SD weight gain of 1.24 ± 2.03 kg. In comparison with participants who received placebo, urine potassium but not serum potassium increased significantly among participants randomly assigned to receive KCl (P = 0.005 and 0.258, respectively). At the end of the study, participants taking KCl had stable or improved fasting glucose, with a mean ± SD change in fasting glucose of -1.1 ± 8.4 mg/dL compared with an increase of 6.1 ± 7.6 mg/dL in those who received placebo (P = 0.03 for comparison between arms). There were no significant differences in glucose or insulin measures during the OGTT between the 2 groups, but there was a trend for improved insulin sensitivity in potassium-treated participants.Conclusions: In this pilot trial, KCl at a dose of 40 mEq/d did not increase serum potassium significantly. However, despite weight gain, KCl prevented worsening of fasting glucose. Further studies in larger sample sizes, as well as with interventions to increase serum potassium more than was achieved with our intervention, are indicated to definitively test this potentially safe and inexpensive approach to reducing diabetes risk. This trial was registered at clinicaltrials.gov as NCT02236598.

Earbud-based sensor for the assessment of energy expenditure, HR, and VO2max.

INTRODUCTION/PURPOSE: The goal of this program was to determine the feasibility of a novel noninvasive, highly miniaturized optomechanical earbud sensor for accurately estimating total energy expenditure (TEE) and maximum oxygen consumption (VO2max). The optomechanical sensor module, small enough to fit inside commercial audio earbuds, was previously developed to provide a seamless way to measure blood flow information during daily life activities. The sensor module was configured to continuously measure physiological information via photoplethysmography and physical activity information via accelerometry. This information was digitized and sent to a microprocessor where digital signal-processing algorithms extract physiological metrics in real time. These metrics were streamed wirelessly from the earbud to a computer. METHODS: In this study, 23 subjects of multiple physical habitus were divided into a training group of 14 subjects and a validation group of 9 subjects. Each subject underwent the same exercise measurement protocol consisting of treadmill-based cardiopulmonary exercise testing to reach VO2max. Benchmark sensors included a 12-lead ECG sensor for measuring HR, a calibrated treadmill for measuring distance and speed, and a gas-exchange analysis instrument for measuring TEE and VO2max. The earbud sensor was the device under test. Benchmark and device under test data collected from the 14-person training data set study were integrated into a preconceived statistical model for correlating benchmark data with earbud sensor data. Coefficients were optimized, and the optimized model was validated in the 9-person validation data set. RESULTS: It was observed that the earbud sensor estimated TEE and VO2max with mean ± SD percent estimation errors of -0.7 ± 7.4% and -3.2 ± 7.3%, respectively. CONCLUSION: The earbud sensor can accurately estimate TEE and VO2max during cardiopulmonary exercise testing.

Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial".

Advancing age is associated with an increase in physical impairment, functional limitations, disability, and loss of independence. Regular physical activity conveys health benefits, but the yield on physical function in the elderly, is less clear. Current exercise guidelines are focused predominantly on aerobic programs despite evidence that age-associated declines are mediated by peripheral tissue changes. The Fit for Life trial proposes a new paradigm of exercise training for the elderly that uses a low-mass high-repetition training regimen specifically focused on peripheral tissue beds or body regions (Regional Specific Training Stimulus - RSTS). RSTS is designed to deliver a localized stimulus to the peripheral vasculature, bone and muscle, without imposing a significant central cardiorespiratory strain. The purpose of this study is three-fold; 1) to derive effect sizes from the RSTS intervention by which to power a subsequent larger, confirmatory trial; 2) to assess fidelity of the RSTS intervention; and 3) to assess the interrelationship of the primary endpoints of physical impairment/fitness (VO(2peak), 1 repetition maximal contraction) and function (Senior Fitness Test scores) following two versions of a 4 + 8 week protocol. Men and women over 70 years, at risk for losing independence will be randomized to either 4 weeks of RSTS or "aerobic" exercise, followed by an identical 8 weeks of progressive whole-body training (aerobic plus resistance). The guiding hypothesis is that the magnitude of adaptation after 12 weeks will be greatest in those initially randomized to RSTS. Possible mediators of the intervention effect - physical impairment/fitness and function relationship, including vascular function, muscle mass, strength, and physiology will also be assessed.

Exercise effects on lipids in persons with varying dietary patterns-does diet matter if they exercise? Responses in Studies of a Targeted Risk Reduction Intervention through Defined Exercise I.

BACKGROUND: The standard clinical approach for reducing cardiovascular disease risk due to dyslipidemia is to prescribe changes in diet and physical activity. The purpose of the current study was to determine if, across a range of dietary patterns, there were variable lipoprotein responses to an aerobic exercise training intervention. METHODS: Subjects were participants in the STRRIDE I, a supervised exercise program in sedentary, overweight subjects randomized to 6 months of inactivity or 1 of 3 aerobic exercise programs. To characterize diet patterns observed during the study, we calculated a modified z-score that included intakes of total fat, saturated fat, trans fatty acids, cholesterol, omega-3 fatty acids, and fiber as compared with the 2006 American Heart Association diet recommendations. Linear models were used to evaluate relationships between diet patterns and exercise effects on lipoproteins/lipids. RESULTS: Independent of diet, exercise had beneficial effects on low-density lipoprotein cholesterol particle number, low-density lipoprotein cholesterol size, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol size, and triglycerides (P < .05 for all). However, having a diet pattern that closely adhered to American Heart Association recommendations was not related to changes in these or any other serum lipids or lipoproteins in any of the exercise groups. CONCLUSIONS: We found that even in sedentary individuals whose habitual diets vary in the extent of adherence to AHA dietary recommendations, a rigorous, supervised exercise intervention can achieve significant beneficial lipid effects.