Effects of aerobic and resistance exercise for 9 months on serum free light chains in type 2 diabetes.

Background and aims: Serum polyclonal free light chains (FLCs) levels are associated with overall survival in the general population, reflecting their utility as a biomarker of underlying immune activation and inflammation. Regular exercise is known to ameliorate low-grade inflammation in chronic diseases such as type 2 diabetes; however, the effects of different exercise training modalities on FLCs in adults with type 2 diabetes is unknown. This study investigated the effects of 9-month of aerobic, resistance or combined supervised exercise on serum FLCs in 164 patients with type 2 diabetes (age 58 ± 8 years; 63% female). Methods: 164 participants from the Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes trial (HART-D) were randomly assigned to no exercise (n = 27), aerobic exercise alone (n = 41), resistance exercise alone (n = 49), or a combination of aerobic and resistance exercise (n = 47). Fasting serum samples were collected before and after completion of the intervention to quantify changes in kappa and lambda FLCs, and serum creatinine, using commercially-available ELISAs. Results: At baseline, combined kappa and lambda FLCs (FLC sum; calculated as kappa + lambda FLCs) were positively correlated with high-sensitive C-reactive protein (hs-CRP) (r = 0.237, p < 0.05) and fat mass (r = 0.162, p < 0.05), and negatively associated with aerobic fitness (r = -0.238, p < 0.05). While non-exercise controls exhibited an increase in FLCs over the 9-month study, exercise training blunted this increase (Δ FLC sum control arm: 3.25 ± 5.07 mg∙L-1 vs. all exercise arms: -0.252 ± 6.60 mg∙L-1, p < 0.05), regardless of exercise modality. Conclusion: Serum FLCs were associated with physical fitness and body composition in patients with type 2 diabetes. 9-month of exercise training prevented the accumulation of FLCs, regardless of exercise modality. Unlike hs-CRP-which did not change during the trial-serum FLCs may serve as a more sensitive biomarker of chronic low-grade inflammation in this population.

A single exposure to 100% normo-baric oxygen therapy appears to improve sequence learning processes by increasing prefrontal cortex oxygen saturation.

Previously, we showed that a normo-baric 100 % oxygen treatment (NbOxTr) enhances motor learning processes, e.g., visuomotor adaptation (VMA) and sequence learning (SL). However, this work was limited to behavioral outcomes and did not identify the physiological mechanistic underpinnings of these improvements. Here, we expand on this research to investigate the effects of a NbOxTr on the oxygen tissue saturation index (TSI) level of the prefrontal cortex (PFC) when performing a SL task and whether potential SL improvements relate to increased TSI levels in the PFC. Twenty four right-handed young, healthy adults were randomly assigned to a NbOxTr group (normo-baric 100 % oxygen, n = 12) or a control group (normal air, n = 12). They received their respective treatments via a nasal cannula during the experiment. Oxygen TSI levels of the right and left PFC were measured via near-infrared spectroscopy (NIRS) throughout different SL task phases (Baseline, Training, Testing). The NbOxTr increased the TSI of the PFC in the Training phase (p < 0.01) and positively affected SL retention in the Testing phase (p < 0.05). We also found a positive correlation between TSI changes in the right PFC during the gas treatment phase (3.4 % increase) and response time (RT) improvements in the SL task training and retention phase (all p < 0.05). Our results suggest that a simple NbOxTr increases the oxygenated hemoglobin availability in the PFC, which appears to mediate the retention of acquired SL improvements in healthy young adults. Future studies should examine treatment-related oxygenation changes in other brain areas involved and their relation to enhanced learning processes. Whether this NbOxTr improves SL in neurologically impaired populations should also be examined.

Blood and MRI biomarkers of mild traumatic brain injury in non-concussed collegiate football players.

Football has one of the highest incidence rates of mild traumatic brain injury (mTBI) among contact sports; however, the effects of repeated sub-concussive head impacts on brain structure and function remain under-studied. We assessed the association between biomarkers of mTBI and structural and functional MRI scans over an entire season among non-concussed NCAA Division I linemen and non-linemen. Concentrations of S100B, GFAP, BDNF, NFL, and NSE were assessed in 48 collegiate football players (32 linemen; 16 non-linemen) before the start of pre-season training (pre-camp), at the end of pre-season training (pre-season), and at the end of the competitive season (post-season). Changes in brain structure and function were assessed in a sub-sample of 11 linemen and 6 non-linemen using structural and functional MRI during the execution of Stroop and attention network tasks. S100B, GFAP and BDNF concentrations were increased at post-season compared to pre-camp in linemen. White matter hyperintensities increased in linemen during pre-season camp training compared to pre-camp. This study showed that the effects of repeated head impacts are detectable in the blood of elite level non-concussed collegiate football players exposed to low-moderate impacts to the heads, which correlated with some neurological outcomes without translating to clinically-relevant changes in brain anatomy or function.

Exercise-induced Changes in Central Adiposity During an RCT: Effect of Exercise Dose and Associations With Compensation.

CONTEXT: Exercise can decrease central adiposity, but the effect of exercise dose and the relationship between central adiposity and exercise-induced compensation is unclear. OBJECTIVE: Test the effect of exercise dose on central adiposity change and the association between central adiposity and exercise-induced weight compensation. METHODS: In this ancillary analysis of a 6-month randomized controlled trial, 170 participants with overweight or obesity (mean ± SD body mass index: 31.5 ± 4.7 kg/m2) were randomized to a control group or exercise groups that reflected exercise recommendations for health (8 kcal/kg/week [KKW]) or weight loss and weight maintenance (20 KKW). Waist circumference was measured, and dual-energy X-ray absorptiometry assessed central adiposity. Predicted weight change was estimated and weight compensation (weight change - predicted weight change) was calculated. RESULTS: Between-group change in waist circumference (control: .0 cm [95% CI, -1.0 to 1.0], 8 KKW: -.7 cm [95% CI, -1.7 to .4], 20 KKW: -1.3 cm [95% CI, -2.4 to -.2]) and visceral adipose tissue (VAT; control: -.02 kg [95% CI, -.07 to .04], 8 KKW: -.01 kg [95% CI, -.07 to .04], 20 KKW: -.04 kg [95% CI, -.10 to .02]) was similar (P ≥ .23). Most exercisers (82.6%) compensated (weight loss less than expected). Exercisers who compensated exhibited a 2.5-cm (95% CI, .8 to 4.2) and .23-kg (95% CI, .14 to .31) increase in waist circumference and VAT, respectively, vs those who did not (P < .01). Desire to eat predicted VAT change during exercise (ß = .21; P = .03). CONCLUSION: In the presence of significant weight compensation, exercise at doses recommended for health and weight loss and weight maintenance leads to negligible changes in central adiposity.

A simple 100% normobaric oxygen treatment can substantially enhance sequence learning processes.

Motor learning processes are crucial for our everyday life, and improving skills by tailored interventions is of great clinical interest and value. Our previous work revealed a positive effect of normo-baric oxygen treatment on visuomotor adaptation. Here, we investigate whether it could positively affect sequence learning (SL) processes as well. Sixty-four healthy young adults were divided into a 100% oxygen treatment (NbOxTr; N = 32, M=20.7 ± 1.63 yrs.) and a normal air treatment (AirTr; N = 32, M=20.8 ± 0.95 yrs.) group. Participants performed a standardized SL task by pressing the spatial-compatible key on a keyboard according to four visual stimuli with two pre-determined 8-item sequences with different training depths. Following a baseline session (10 trials), both groups received a gas treatment (5 L/min, via nasal cannula) during the next training session (4 blocks, 45 trials each block), followed by a testing session (30 trials) without gas treatment. On day two, participants completed another 30 trials, similar to the first-day testing session, also without gas treatment. ANOVA revealed no significant group differences during baseline (p > 0.05) but a significantly faster response time (+45.5%) in the NbOxTr than AirTr group in the training session with gas treatment for all training depths (p < 0.05). The positive NbOxTr effect consolidated into the following testing session without gas treatment for deeply trained sequences (+17%; p < 0.05), and for all training depth on day-two testing (+45.2%; p < 0.05). Results suggest that the NbOxTr substantially improved participants' SL processing speed. Notably, improvements consolidated after an overnight sleep. The present work confirms a beneficial effect of a single, simple NbOxTr on fundamental motor learning processes. This treatment approach may provide promising implications for practice in neurological rehabilitation and other motor learning-related scenarios and should be further investigated in future research.

Boost your brain: a simple 100% normobaric oxygen treatment improves human motor learning processes.

Introduction: Human motor learning processes are a fundamental part of our daily lives and can be adversely affected by neurologic conditions. Motor learning largely depends on successfully integrating cognitive and motor-related sensory information, and a simple, easily accessible treatment that could enhance such processes would be exciting and clinically impactful. Normobaric 100% oxygen treatment (NbOxTr) is often used as a first-line intervention to improve survival rates of brain cells in neurological trauma, and recent work indicates that improvements in elements crucial for cognitive-motor-related functions can occur during NbOxTr. However, whether NbOxTr can enhance the motor learning processes of healthy human brains is unknown. Here, we investigated whether a brief NbOxTr administered via nasal cannula improves motor learning processes during a visuomotor adaptation task where participants adapt to a visual distortion between visual feedback and hand movements. Methods: 40 healthy young adults (M = 21 years) were randomly assigned to a NbOxTr (N = 20; 100% oxygen) or air (N = 20; regular air) group and went through four typical visuomotor adaptation phases (Baseline, Adaptation, After-Effect, Refresher). Gas treatment (flow rate 5 L/min) was only administered during the Adaptation phase of the visuomotor experiment, in both groups. Results: The NbOxTr provided during the Adaptation phase led to significantly faster and about 30% improved learning (p < 0.05). Notably, these motor learning improvements consolidated into the subsequent experiment phases, i.e., after the gas treatment was terminated (p < 0.05). Discussion: We conclude that this simple and brief NbOxTr dramatically improved fundamental human motor learning processes and may provide promising potential for neurorehabilitation and skill-learning approaches. Further studies should investigate whether similar improvements exist in elderly and neurologically impaired individuals, other motor learning tasks, and also long-lasting effects.

Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 2 diabetes in people in the healthy weight BMI category (<25 kg/m2), herein defined as 'normal-weight type 2 diabetes', is associated with sarcopenia (low muscle mass). Given this unique body composition, the optimal exercise regimen for this population is unknown. METHODS: We conducted a parallel-group RCT in individuals with type 2 diabetes (age 18-80 years, HbA1c 47.5-118.56 mmol/mol [6.5-13.0%]) and BMI <25 kg/m2). Participants were recruited in outpatient clinics or through advertisements and randomly assigned to a 9 month exercise programme of strength training alone (ST), aerobic training alone (AER) or both interventions combined (COMB). We used stratified block randomisation with a randomly selected block size. Researchers and caregivers were blinded to participants' treatment group; however, participants themselves were not. Exercise interventions were conducted at community-based fitness centres. The primary outcome was absolute change in HbA1c level within and across the three groups at 3, 6 and 9 months. Secondary outcomes included changes in body composition at 9 months. Per adherence to recommended exercise protocol (PP) analysis included participants who completed at least 50% of the sessions. RESULTS: Among 186 individuals (ST, n=63; AER, n=58; COMB, n=65) analysed, the median (IQR) age was 59 (53-66) years, 60% were men and 83% were Asian. The mean (SD) HbA1c level at baseline was 59.6 (13.1) mmol/mol (7.6% [1.2%]). In intention-to-treat analysis, the ST group showed a significant decrease in HbA1c levels (mean [95% CI] -0.44 percentage points [-0.78, -0.12], p=0.002), while no significant change was observed in either the COMB group (-0.35 percentage points, p=0.13) or the AER group (-0.24 percentage points, p=0.10). The ST group had a greater improvement in HbA1c levels than the AER group (p=0.01). Appendicular lean mass relative to fat mass increased only in the ST group (p=0.0008), which was an independent predictor of HbA1c change (beta coefficient -7.16, p=0.01). Similar results were observed in PP analysis. Only one adverse event, in the COMB group, was considered to be possibly associated with the exercise intervention. CONCLUSIONS/INTERPRETATION: In normal-weight type 2 diabetes, strength training was superior to aerobic training alone, while no significant difference was observed between strength training and combination training for HbA1c reduction. Increased lean mass relative to decreased fat mass was an independent predictor of reduction in HbA1c level. TRIAL REGISTRATION: ClinicalTrials.gov NCT02448498. FUNDING: This study was funded by the National Institutes of Health (NIH; R01DK081371).

Acute Exercise Increases NK Cell Mitochondrial Respiration and Cytotoxicity against Triple-Negative Breast Cancer Cells under Hypoxic Conditions.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive, highly metastatic malignancy with high recurrence rates. Hypoxia is a hallmark of the TNBC tumor microenvironment, which promotes tumor growth while impairing natural killer (NK) cell cytotoxic functions. Although acute exercise improves NK cell function under normoxic conditions, the effect of exercise on NK cell cytotoxic functions under hypoxic conditions mimicking O 2 tensions observed in solid tumors is unknown. METHODS: The cytotoxic functions of resting and postexercise NK cells isolated from thirteen young inactive healthy women were assessed against breast cancer cells expressing different levels of hormone receptors (MCF-7 and MDA-MB-231) under normoxic and hypoxic conditions. Mitochondrial respiration and H 2 O 2 efflux rates of the TNBC-activated NK cells were assessed via high-resolution respirometry. RESULTS: Under hypoxia, postexercise NK cells exhibited greater killing of TNBC than resting NK cells. Further, postexercise NK cells were more likely to kill TNBC under hypoxia than normoxic conditions. In addition, mitochondrial respiration associated with oxidative (OXPHOS) capacity of TNBC-activated NK cells was greater in postexercise cells than resting cells under normoxia, but not under hypoxia. Finally, acute exercise was associated with reduced mitochondrial H 2 O 2 efflux by NK cells in both conditions. CONCLUSIONS: Together, we present crucial interrelationships between hypoxia and exercise-induced changes in NK cell functions against TNBC cells. By modulating their mitochondrial bioenergetic functions, we postulate that acute exercise improves NK cell function under hypoxic conditions. Specifically, NK cell O 2 and H 2 O 2 flow (pmol·s -1 ·million NK cells -1 ) changes in response to 30-min cycling suggest that exercise primes NK cell tumor killing by reducing mitochondrial oxidative stress and, thus, rescuing their function when exposed to harsh hypoxic environments as observed in the microenvironment of breast solid tumors.

Seasonal changes in physiological and psychological parameters of stress in collegiate swimmers.

To investigate the seasonal changes in physiological and psychological parameters of stress in collegiate swimmers. Fifteen NCAA Division I swimmers (8 men) participated in a tethered anaerobic swim test to determine physiological responses in an ecologically-relevant, graded exercise test. Wisconsin Upper Respiratory Symptom Survey (WURSS-21), Activation-Deactivation Adjective Check List (AD-ACL), Daily Analysis of Life Demands of Athletes (DALDA), and Pittsburgh Sleep Quality Index were assessed at post-season in April (V1), the end of off-season in June (V2), and pre-season in October (V3). The percent change was determined from V2-V1 (off-season phase), V3-V2 (pre-season phase), V1-V3 (in-season phase). Spearman's rho correlation was used to examine associations between change in physiological and psychological outcomes. All data results showed a better swim performance occurred at V2. Men tended to have faster speed (p = 0.07) in fewer strokes (p = 0.10) and greater work per stroke (p = 0.10) at V2 than V1. Women were faster during V2 compared to V1 (p = 0.02) and V3 (p = 0.05). Women had fewer strokes (p = 0.02) and greater work per stroke (p = 0.01) at V2 compared to V3. Women had the lowest HR and lactate concentration at V3 compared to other visits (p < 0.05). During the in-season phase, swim speed decreased the greatest extent and stress sources and symptoms assessed by DALDA had greatest elevation (p < 0.05). An increased in stress sources and symptoms assessed by DALDA was associated with an increase in upper respiratory illness from WURSS-21 (rho = 0.44, p = 0.009), being less energetic (rho = - 0.35, p = 0.04) and greater tension state (rho = 0.49, p = 0.003; AD-ACL), and a decrease in swim speed (rho =- 0.38, p = 0.03). Swim performance peaked at off-season when psychological stress was at its lowest. The relationship between DALDA scores with psychological parameters and swim performance suggested physiological and psychological parameters of stress is an important aspect to avoid overtraining when approaching high swim performance.

An aerobic exercise intervention to improve metabolic health among people living with HIV with at-risk alcohol use: the ALIVE-Ex research study protocol.

BACKGROUND: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. METHODS: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention is a moderate intensity aerobic exercise protocol implemented 3 days per week for 10 weeks at the Louisiana State University Health Sciences Center-New Orleans. Participants who have a fasting blood glucose level between 94 and 125 mg/dl will be enrolled in the study. Oral glucose tolerance tests, fitness assessments, and skeletal muscle biopsies will be performed pre- and post-exercise intervention. The primary outcome is to determine whether the exercise protocol improves measures of whole-body glucose-insulin dynamics, cardiorespiratory fitness, and skeletal muscle metabolic and bioenergetic function. Secondary outcomes are to determine whether the exercise intervention improves cognitive function and overall quality of life. Results generated will demonstrate the effect of exercise on glycemic measures in PLWH with subclinical dysglycemia and at-risk alcohol use. CONCLUSIONS: The proposed intervention will also have the potential to be scalable to promote lifestyle changes among PLWH, particularly in underserved communities.

Impact of maximal exercise on immune cell mobilization and bioenergetics.

Acute aerobic exercise increases the number and proportions of circulating peripheral blood mononuclear cells (PMBC) and can alter PBMC mitochondrial bioenergetics. In this study, we aimed to examine the impact of a maximal exercise bout on immune cell metabolism in collegiate swimmers. Eleven (7 M/4F) collegiate swimmers completed a maximal exercise test to measure anaerobic power and capacity. Pre- and postexercise PBMCs were isolated to measure the immune cell phenotypes and mitochondrial bioenergetics using flow cytometry and high-resolution respirometry. The maximal exercise bout increased circulating levels of PBMCs, particularly in central memory (KLRG1+/CD57-) and senescent (KLRG1+/CD57+) CD8+ T cells, whether measured as a % of PMBCs or as absolute concentrations (all p < 0.05). At the cellularlevel, the routine oxygen flow (IO2 [pmol·s-1 ·106 PBMCs-1 ]) increased following maximal exercise (p = 0.042); however, there were no effects of exercise on the IO2 measured under the LEAK, oxidative phosphorylation (OXPHOS), or electron transfer (ET) capacities. There were exercise-induced increases in the tissue-level oxygen flow (IO2-tissue [pmol·s-1 ·mL blood-1 ]) for all respiratory states (all p < 0.01), except for the LEAK state, after accounting for the mobilization of PBMCs. Future subtype-specific studies are needed to characterize further maximal exercise's true impact on immune cell bioenergetics.

Bioelectrical impedance phase angle is associated with physical performance before but not after simulated multi-stressor military operations.

Physical performance decrements observed during multi-stressor military operations may be attributed, in part, to cellular membrane dysfunction, which is quantifiable using phase angle (PhA) derived from bioelectrical impedance analysis (BIA). Positive relationships between PhA and performance have been previously reported in cross-sectional studies and following longitudinal exercise training programs, but whether changes in PhA are indicative of acute decrements in performance during military operations is unknown. Data from the Optimizing Performance for Soldiers II study, a clinical trial examining the effects of exogenous testosterone administration on body composition and performance during military stress, was used to evaluate changes in PhA and their associations with physical performance. Recreationally active, healthy males (n = 34; 26.6 ± 4.3 years; 77.9 ± 12.4 kg) were randomized to receive testosterone undecanoate or placebo before a 20-day simulated military operation, which was followed by a 23-day recovery period. PhA of the whole-body (Whole) and legs (Legs) and physical performance were measured before (PRE) and after (POST) the simulated military operation as well as in recovery (REC). Independent of treatment, PhAWhole and PhALegs decreased from PRE to POST (p < 0.001), and PhALegs , but not PhAWhole , remained lower at REC than PRE. PhAWhole at PRE and REC were associated with vertical jump height and Wingate peak power (p < 0.001-0.050), and PhAWhole at PRE was also associated with 3-RM deadlift mass (p = 0.006). However, PhA at POST and changes in PhA from PRE to POST were not correlated with any performance measure (p > 0.05). Additionally, PhA was not associated with aerobic performance at any timepoint. In conclusion, reduced PhA from PRE to POST provides indirect evidence of cellular membrane disruption. Associations between PhA and strength and power were only evident at PRE and REC, suggesting PhA may be a useful indicator of strength and power, but not aerobic capacity, in non-stressed conditions, and not a reliable indicator of physical performance during severe physiological stress.

Monitoring body composition change for intervention studies with advancing 3D optical imaging technology in comparison to dual-energy X-ray absorptiometry.

BACKGROUND: Recent 3-dimensional optical (3DO) imaging advancements have provided more accessible, affordable, and self-operating opportunities for assessing body composition. 3DO is accurate and precise in clinical measures made by DXA. However, the sensitivity for monitoring body composition change over time with 3DO body shape imaging is unknown. OBJECTIVES: This study aimed to evaluate the ability of 3DO in monitoring body composition changes across multiple intervention studies. METHODS: A retrospective analysis was performed using intervention studies on healthy adults that were complimentary to the cross-sectional study, Shape Up! Adults. Each participant received a DXA (Hologic Discovery/A system) and 3DO (Fit3D ProScanner) scan at the baseline and follow-up. 3DO meshes were digitally registered and reposed using Meshcapade to standardize the vertices and pose. Using an established statistical shape model, each 3DO mesh was transformed into principal components, which were used to predict whole-body and regional body composition values using published equations. Body composition changes (follow-up minus the baseline) were compared with those of DXA using a linear regression analysis. RESULTS: The analysis included 133 participants (45 females) in 6 studies. The mean (SD) length of follow-up was 13 (5) wk (range: 3-23 wk). Agreement between 3DO and DXA (R2) for changes in total FM, total FFM, and appendicular lean mass were 0.86, 0.73, and 0.70, with root mean squared errors (RMSEs) of 1.98 kg, 1.58 kg, and 0.37 kg, in females and 0.75, 0.75, and 0.52 with RMSEs of 2.31 kg, 1.77 kg, and 0.52 kg, in males, respectively. Further adjustment with demographic descriptors improved the 3DO change agreement to changes observed with DXA. CONCLUSIONS: Compared with DXA, 3DO was highly sensitive in detecting body shape changes over time. The 3DO method was sensitive enough to detect even small changes in body composition during intervention studies. The safety and accessibility of 3DO allows users to self-monitor on a frequent basis throughout interventions. This trial was registered at clinicaltrials.gov as NCT03637855 (Shape Up! Adults; https://clinicaltrials.gov/ct2/show/NCT03637855); NCT03394664 (Macronutrients and Body Fat Accumulation: A Mechanistic Feeding Study; https://clinicaltrials.gov/ct2/show/NCT03394664); NCT03771417 (Resistance Exercise and Low-Intensity Physical Activity Breaks in Sedentary Time to Improve Muscle and Cardiometabolic Health; https://clinicaltrials.gov/ct2/show/NCT03771417); NCT03393195 (Time Restricted Eating on Weight Loss; https://clinicaltrials.gov/ct2/show/NCT03393195), and NCT04120363 (Trial of Testosterone Undecanoate for Optimizing Performance During Military Operations; https://clinicaltrials.gov/ct2/show/NCT04120363).

Effectiveness of a Community-Based Structured Physical Activity Program for Adults With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: The efficacy of physical activity interventions among individuals with type 2 diabetes has been established; however, practical approaches to translate and extend these findings into community settings have not been well explored. Objective: To test the effectiveness of providing varying frequencies of weekly structured exercise sessions to improve diabetes control. Design, Setting, and Participants: The IMPACT (Initiate and Maintain Physical Activity in Communities Trial) study was a controlled randomized clinical trial (randomization occurred from October 2016 to April 2019) that included a 6-month, structured exercise intervention either once or thrice weekly vs usual care (UC; advice only). The exercise intervention was conducted at community-based fitness centers. Follow-up visits were conducted in a university research clinic. Participants included adults with type 2 diabetes (hemoglobin A1c [HbA1c] 6.5%-13.0%, not taking insulin, and no precluding health issues). Data analysis was performed from January to April 2022. Interventions: A once-weekly structured exercise group, a thrice-weekly structured exercise group, or UC. Main Outcomes and Measures: The primary outcome was HbA1c at 6 months. Results: A total of 357 participants (143 women [40.1%]) with a mean (SD) age of 57.4 (11.1) years were randomized (119 each to the UC, once-weekly exercise, and thrice-weekly exercise groups). There was no significant difference in HbA1c change by study group in the intention-to-treat analysis at 6 months. Specifically, HbA1c changed by -0.23% (95% CI, -0.48% to 0.01%) in the thrice-weekly exercise group and by -0.16% (95% CI, -0.41% to 0.09%) in the once-weekly exercise group. A total of 62 participants (52.1%) in the once-weekly exercise group and 56 participants (47.1%) in the thrice-weekly exercise group were at least 50% adherent to the assigned structured exercise regimen and were included in the per-protocol analysis. Per-protocol analysis showed that HbA1c changed by -0.35% (95% CI, -0.60% to -0.10%; P = .005) at 3 months and by -0.38% (95% CI, -0.65% to -0.12%; P = .005) at 6 months in the thrice-weekly exercise group compared with UC. There was no significant decrease in HbA1c in the once-weekly exercise group. The exercise intervention was effective in improving self-reported minutes of metabolic equivalent tasks per week for participants in the thrice-weekly exercise group (both overall and per protocol). Conclusions and Relevance: Although the intervention was not effective in the intention-to-treat analysis, participants in the thrice-weekly exercise group who attended at least 50% of the sessions during the 6-month exercise intervention program improved HbA1c levels at 6 months. Future efforts should focus on improving adherence to thrice-weekly structured exercise programs to meet exercise guidelines. Trial Registration: ClinicalTrials.gov Identifier: NCT02061579.

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. We implemented a Bayesian framework to: (1) test the hypothesis of interindividual differences in trainability by comparing variability in change scores between exercise and control using Bayes factors; and (2) compare posterior predictions of control and exercise across a range of moderators (baseline body mass index (BMI) and exercise duration, intensity, amount, mode, and adherence) to estimate the proportions of participants expected to exceed minimum clinically important differences (MCIDs) for all three outcomes. Bayes factors demonstrated a lack of evidence supporting a high degree of variance attributable to interindividual differences in trainability across all three outcomes. These findings indicate that interindividual variability in observed changes are likely due to measurement error and external behavioural factors, not interindividual differences in trainability. Additionally, we found that a larger proportion of exercise participants were expected to exceed MCIDs compared with controls for all three outcomes. Moderator analyses identified that larger proportions were associated with a range of factors consistent with standard exercise theory and were driven by mean changes. Practitioners should prescribe exercise interventions known to elicit large mean changes to increase the probability that individuals will experience beneficial changes in CRF, waist circumference and body mass.

Testosterone undecanoate administration prevents declines in fat-free mass but not physical performance during simulated multi-stressor military operations.

Male military personnel conducting strenuous operations experience reduced testosterone concentrations, muscle mass, and physical performance. Pharmacological restoration of normal testosterone concentrations may attenuate performance decrements by mitigating muscle mass loss. Previously, administering testosterone enanthate (200 mg/wk) during 28 days of energy deficit prompted supraphysiological testosterone concentrations and lean mass gain without preventing isokinetic/isometric deterioration. Whether administering a practical dose of testosterone protects muscle and performance during strenuous operations is undetermined. The objective of this study was to test the effects of a single dose of testosterone undecanoate on body composition and military-relevant physical performance during a simulated operation. After a 7-day baseline phase (P1), 32 males (means ± SD; 77.1 ± 12.3 kg, 26.5 ± 4.4 yr) received a single dose of either testosterone undecanoate (750 mg; TEST) or placebo (PLA) before a 20-day simulated military operation (P2), followed by a 23-day recovery (P3). Assessments included body composition and physical performance at the end of each phase and circulating endocrine biomarkers throughout the study. Total and free testosterone concentrations in TEST were greater than PLA throughout most of P2 (P < 0.05), but returned to P1 values during P3. Fat-free mass (FFM) was maintained from P1 to P2 in TEST (means ± SE; 0.41 ± 0.65 kg, P = 0.53), but decreased in PLA (-1.85 ± 0.69 kg, P = 0.01) and recovered in P3. Regardless of treatment, total body mass and fat mass decreased from P1 to P2 (P < 0.05), but did not fully recover by P3. Physical performance decreased during P2 (P < 0.05) and recovered by P3, regardless of treatment. In conclusion, administering testosterone undecanoate before a simulated military operation protected FFM but did not prevent decrements in physical performance.NEW & NOTEWORTHY This study demonstrated that a single intramuscular dose of testosterone undecanoate (750 mg) administered to physically active males before a 20-day simulated, multi-stressor military operation increased circulating total and free testosterone concentrations within normal physiological ranges and spared FFM. However, testosterone administration did not attenuate decrements in physical performance across multiple measures of power, strength, anaerobic or aerobic capacity.

Salivary immunity of elite collegiate American football players infected with SARS-CoV-2 normalizes following isolation.

The impact of COVID-19 on systemic immunity in the general population has been well characterized, however the short-term effects of COVID-19 infection on innate salivary immunity in elite-level athletes are unknown. Therefore, this study aimed to determine whether elite college football athletes had altered salivary immunity following the CDC-recommended isolation post-SARS-CoV-2 infection. Salivary samples were obtained from fourteen elite football players who tested positive for SARS-CoV-2 (n = 14), immediately after CDC-recommended isolation (average days = 14 ± 2 days) and fifteen controls who remained uninfected with SARS-CoV-2. Biomarkers of innate salivary immunity (sIgA and alpha-amylase), antimicrobial proteins (AMPs, i.e., HNP1-3, lactoferrin, LL-37) and lung inflammation (SPA, SPLI, and Neutrophil Elastase-alpha-1-antitrypsin complex) were measured. Independent student t-tests were used to determine changes in biomarkers between groups. Although all AMP levels were within normal range, Human Neutrophil Defensin 1-3 concentrations and secretion rates were higher in SARS-CoV-2+ compared to SARS-CoV-2-. This suggests that the CDC-recommended isolation period is sufficient to ensure that athletes' salivary immunity is not compromised upon return to sports, and athletes post-COVID-19 infection do not appear to be at greater risk for secondary infection than those with no history of COVID-19.

Predictors of Post-Exercise Energy Intake in Adolescents Ranging in Weight Status from Overweight to Severe Obesity.

Exercise may sensitize individuals with overweight and obesity to appetitive signals (e.g., hunger and fullness cues), overriding trait eating behaviors that contribute to overeating and obesity, such as uncontrolled eating. The objective of the current study was to measure predictors of objective ad libitum energy intake at a laboratory-based, post-exercise test-meal in adolescents ranging in weight status from overweight to severe obesity. We hypothesized that appetitive states, rather than appetitive traits, would be the strongest predictors of energy intake at a post-exercise test-meal, after controlling for body size. At Baseline, 30 adolescents (ages 10-16 years, 50% female (F), 43% non-Hispanic white (NHW), 83% with obesity (OB)) completed state and trait appetite measures and an ad libitum dinner meal following intensive exercise. Nineteen of those participants (47% F, 32% NHW, 79% OB) completed identical assessments two years later (Year 2). Energy intake (kcal) at each time point was adjusted for fat-free mass index (i.e., body size). Adjusted energy intake was reliable from Baseline to Year 2 (ICC = 0.84). Multiple pre-meal appetite ratings were associated with test-meal energy intake. In stepwise linear regression models, pre-meal prospective food consumption was the strongest and only significant predictor of test-meal energy intake at both Baseline (R2 = 0.25, p = 0.005) and Year 2 (R2 = 0.41, p = 0.003). Baseline post-exercise energy intake was associated with weight change over two years (R2 = 0.24, p = 0.04), but not with change in fat mass (p = 0.11). Appetitive traits were not associated with weight or body composition change (p > 0.22). State appetite cues were the strongest predictors of post-exercise energy intake, independent of body size. Future studies should examine whether long-term exercise programs enhance responsiveness to homeostatic appetite signals in youth with overweight and obesity, with a goal to reduce excess energy intake and risk for weight gain over time.

Impact of a Novel Training Approach on Hemodynamic and Vascular Profiles in Older Adults.

Exercise training beneficially moderates the effects of vascular aging. This study compared the efficacy of Peripheral Remodeling through Intermittent Muscular Exercise (PRIME), a novel training regimen, versus aerobic training on hemodynamic profiles in participants ≥70 years at risk for losing functional independence. Seventy-five participants (52 females, age: 76 ± 5 years) were assessed for hemodynamic and vascular function at baseline, after 4 weeks of either PRIME or aerobic training (Phase 1) and again after a further 8 weeks of aerobic and resistance training (Phase 2). Data were analyzed using 2 × 2 repeated-measures analysis of variance models on the change in each dependent variable. PRIME demonstrated reductions in brachial and aortic mean arterial pressure and diastolic blood pressure (p < .05) from baseline after Phase 1, which were sustained throughout Phase 2. Earlier and greater reductions in blood pressure following PRIME support the proposal that peripheral muscular training could beneficial for older individuals commencing an exercise program.