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. Although 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 multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity.

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 ); 2) high-amount/moderate-intensity (16 kcal/kg/week at 50% peak ); 3) high-amount/vigorous-intensity (16 kcal/kg/week at 75% peak ); or 4) diet (7% weight loss) plus low-amount/moderate-intensity (10 kcal/kg/week at 50% peak ). The primary outcome of this secondary analysis was change in the MetS z-score.

Differential Effects of Amount, Intensity, and Mode of Exercise Training on Insulin Sensitivity and Glucose Homeostasis: A Narrative Review.

As type 2 diabetes remains a leading cause of morbidity and mortality, identifying the most appropriate preventive treatment early in the development of disease is an important public health matter. In general, lifestyle interventions incorporating exercise and weight loss via caloric restriction improve cardiometabolic risk by impacting several key markers of insulin sensitivity and glucose homeostasis. However, variations in the effects of specific types of exercise interventions on these markers have led to conflicting results surrounding the optimal amount, intensity, and mode of exercise for optimal effects.

Interindividual Differences in Trainability and Moderators of Cardiorespiratory Fitness, Waist Circumference, and Body Mass Responses: A Large-Scale Individual Participant Data Meta-analysis.

Although many studies have assumed variability reflects variance caused by exercise training, few studies have examined whether interindividual differences in trainability are present following exercise training. The present individual participant data (IPD) meta-analysis sought to: (1) investigate the presence of interindividual differences in trainability for cardiorespiratory fitness (CRF), waist circumference, and body mass; and (2) examine the influence of exercise training and potential moderators on the probability that an individual will experience clinically important differences. The IPD meta-analysis combined data from 1879 participants from eight previously published randomized controlled trials.

GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1.

Context: Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4).

Amount and intensity effects of exercise training alone versus a combined diet and exercise lifestyle intervention on health-related quality of life in the STRRIDE-PD randomized trial.

Introduction: To determine the relative contributions of various amounts and intensities of exercise alone to a combined lifestyle intervention on health-related quality of life (HrQoL) measures.

Research Design And Methods: Participants (n=162) were sedentary, overweight/obese, with pre-diabetes, and randomized to one of four 6-month interventions: (1) high amount/moderate intensity exercise-energy expenditure of 16 kcal/kg of body weight/week (KKW) at 50% oxygen consumption (V̇O) reserve; (2) high/vigorous-16 KKW at 75% V̇O reserve; (3) low/moderate-10 KKW at 50% V̇O reserve; (4) low/moderate plus diet-10 KKW at 50% V̇O reserve plus a calorically restricted diet. The 36-Item Short-Form Survey (SF-36) and Satisfaction with Physical Function and Appearance (SPF/SPA) survey were assessed at baseline and post-intervention.

Aerobic Versus Resistance Training Effects on Ventricular-Arterial Coupling and Vascular Function in the STRRIDE-AT/RT Trial.

The goal was studying the differential effects of aerobic training (AT) vs. resistance training (RT) on cardiac and peripheral arterial capacity on cardiopulmonary (CP) and peripheral vascular (PV) function in sedentary and obese adults. In a prospective randomized controlled trial, we studied the effects of 6 months of AT vs.

Exploring Differences in Cardiorespiratory Fitness Response Rates Across Varying Doses of Exercise Training: A Retrospective Analysis of Eight Randomized Controlled Trials.

Objective: This study tested the hypothesis that greater mean changes in cardiorespiratory fitness (CRF), in either the absence or presence of reduced interindividual variability, explain larger CRF response rates following higher doses of exercise training.

Methods: We retrospectively analyzed CRF data from eight randomized controlled trials (RCT; n = 1590 participants) that compared at least two doses of exercise training. CRF response rates were calculated as the proportion of participants with individual confidence intervals (CIs) placed around their observed response that lay above 0.

Aerobic, Resistance, and Combination Training on Health-Related Quality of Life: The STRRIDE-AT/RT Randomized Trial.

The main purpose of this study was to determine the differential effects of aerobic training (AT), resistance training (RT), and a combination of aerobic and resistance training (AT/RT) on changes in self-rated HrQoL measures, including the Short-Form 36 (SF-36) survey and Satisfaction with Physical Function and Appearance survey. We also sought to determine if combination training (AT/RT) has a more or less additive effect compared to AT or RT alone on self-rated HrQoL measures. Participants ( = 137) completed one of three 8-month exercise interventions: (1) AT: 14 kcal exercise expenditure per kg of body weight per week (KKW; equivalent to roughly 12 miles/week) at 65-80% of peak oxygen consumption; (2) RT: 3 days per week, 8 exercises, 3 sets per exercise, 8-12 repetitions per set; (3) AT/RT: full combination of the AT and RT interventions.

Effects of Amount, Intensity, and Mode of Exercise Training on Insulin Resistance and Type 2 Diabetes Risk in the STRRIDE Randomized Trials.

Background: Lipoprotein Insulin Resistance Index (LP-IR) and Diabetes Risk Index are novel spectroscopic multimarkers of insulin resistance and type 2 diabetes risk. As the Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) randomized trials have previously demonstrated the ability of exercise training to improve traditional markers of insulin action, the aim of this study was to examine the effects of exercise amount, intensity, and mode on LP-IR and the Diabetes Risk Index.

Methods: A total of 503 adults with dyslipidemia [STRRIDE I ( = 194), STRRIDE AT/RT ( = 139)] or prediabetes [STRRIDE-PD ( = 170)] were randomized to control or one of 10 exercise interventions, ranging from doses of 8-23 kcal/kg/week; intensities of 50-75% V̇O; and durations of 6-8 months.

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.

Rejuvenation of Neutrophil Functions in Association With Reduced Diabetes Risk Following Ten Weeks of Low-Volume High Intensity Interval Walking in Older Adults With Prediabetes - A Pilot Study.

Neutrophil dysfunction is a common feature of aging, and is associated with the pathogenesis of many age-related diseases, including type 2 diabetes mellitus (T2DM). Although exercise training improves metabolic health, decreases risk of T2DM, and is associated with improving neutrophil functions, involvement in regular physical activity declines with age. The aim of this study was to determine if neutrophil functions could be improved in association with changes in fitness and metabolic parameters in older adults at risk for T2DM using 10-weeks of low volume high-intensity interval exercise training (HIIT).

Evaluating Individual Level Responses to Exercise for Health Outcomes in Overweight or Obese Adults.

Background: Understanding group responses to a given exercise exposure is becoming better developed; however, understanding of individual responses to specific exercise exposures is significantly underdeveloped and must advance before personalized exercise medicine can become a functional reality. Herein, utilizing data from the STRRIDE studies, we address some of the key issues surrounding our efforts to develop better understanding of individual exercise responsiveness.

Methods: We assessed individual cardiometabolic and cardiorespiratory fitness responses in subjects successfully completing STRRIDE I ( = 227) and STRRIDE II ( = 155).

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.

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).

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

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.

Effects of regular endurance exercise on GlycA: Combined analysis of 14 exercise interventions.

Background And Aims: GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions.

A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease.

Genome-wide association studies (GWAS), relying on hundreds of thousands of individuals, have revealed >200 genomic loci linked to metabolic disease (MD). Loss of insulin sensitivity (IS) is a key component of MD and we hypothesized that discovery of a robust IS transcriptome would help reveal the underlying genomic structure of MD. Using 1,012 human skeletal muscle samples, detailed physiology and a tissue-optimized approach for the quantification of coding (>18,000) and non-coding (>15,000) RNA (ncRNA), we identified 332 fasting IS-related genes (CORE-IS).

Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited.

Effects of aerobic training with and without weight loss on insulin sensitivity and lipids.

Purpose: The purpose of this study is to evaluate the effect of exercise training with modest or greater weight loss (≥3%) or not (<3%) on insulin sensitivity, lipoprotein concentrations, and lipoprotein particle size in overweight and obese participants.

Methods: Adults (N = 163, body mass index: 25-37 [kg/m2]) participated in 8 months of exercise training. Insulin sensitivity, lipid concentrations, lipid particle size and other cardiometabolic variables were measured at baseline and follow-up.

Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function.

Objective: Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we examined the effects of different doses of exercise on 3 measures of HDL function in 2 randomized clinical exercise trials.

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

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. We sought to determine the effects of potassium chloride (KCl) supplements, at a commonly prescribed dose, on measures of potassium and glucose metabolism.

Association of the Composite Inflammatory Biomarker GlycA, with Exercise-Induced Changes in Body Habitus in Men and Women with Prediabetes.

GlycA is a new composite measure of systemic inflammation and a predictor of many inflammatory diseases. GlycA is the nuclear magnetic resonance spectroscopy-derived signal arising from glucosamine residues on acute-phase proteins. This study aimed to evaluate how exercise-based lifestyle interventions modulate GlycA in persons at risk for type 2 diabetes.

The Effect of Vigorous- Versus Moderate-Intensity Aerobic Exercise on Insulin Action.

Due to the beneficial effects on a wide range of modern medical conditions, most professional societies recommend regular aerobic exercise as part of a healthy lifestyle. Many of the exercise-related health benefits exhibit a dose-response relationship: Up to a point, more exercise is more beneficial. However, recent studies have suggested that different exercise intensities may provide distinct health benefits, independent of energy expenditure (i.