Directions for Exercise Treatment Response Heterogeneity and Individual Response Research.

Treatment response heterogeneity and individual responses following exercise training are topics of interest for personalized medicine. Proposed methods to determine the contribution of exercise to the magnitude of treatment response heterogeneity and categorizing participants have expanded and evolved. Setting clear research objectives and having a comprehensive understanding of the strengths and weaknesses of the available methods are vital to ensure the correct study design and analytical approach are used. Doing so will ensure contributions to the field are conducted as rigorously as possible. Nonetheless, concerns have emerged regarding the ability to truly isolate the impact of exercise training, and the nature of individual responses in relation to mean group changes. The purpose of this review is threefold. First, the strengths and limitations associated with current methods for quantifying the contribution of exercise to observed treatment response heterogeneity will be discussed. Second, current methods used to categorize participants based on their response to exercise will be outlined, as well as proposed mechanisms for factors that contribute to response variation. Finally, this review will provide an overview of some current issues at the forefront of individual response research.

The ability of exercise to meaningfully improve glucose tolerance in people living with prediabetes: A meta-analysis.

BACKGROUND: Individuals with prediabetes are likely to progress to Type 2 diabetes. Although exercise training is an established method to improve glycemic control, the degree to which this translates into meaningful improvements, particularly in individuals with prediabetes, is unclear. The purpose of this meta-analysis was to investigate the ability of exercise training to improve 2-hour glucose tolerance beyond the smallest worthwhile difference in individuals with prediabetes. It was hypothesized that the majority of implemented exercise programs designed for individuals with prediabetes would not result in meaningful improvements in glucose tolerance. METHODS: Searches were performed in MEDLINE, The Cumulative Index to Nursing and Allied Health Literature, SPORTDiscus, and the Cochrane Library. Included studies reported glucose tolerance using a 2-hour oral glucose tolerance test at baseline and post-intervention; implemented an exercise program lasting at least 12 weeks; and included adults living with prediabetes. Mean effect summaries were determined using random-effects models. Magnitude-based inference statistic was used to estimate the likelihood that observed changes in glucose tolerance were meaningful to patients. RESULTS: Nine articles were included in the meta-analysis, producing 12 independent exercise interventions. The interventions led to an average improvement in glucose tolerance of 5.9% (95% confidence interval: 3.7%-8.0%). Seven (58%) exercise interventions were deemed likely to benefit patients, whereas five (42%) had trivial or unclear findings. CONCLUSION: While exercise intervention led to statistically significant improvements in 2-hour glucose tolerance, the benefit for individuals living with prediabetes remains unclear. Further research is needed to delineate optimal prescription parameters for generating meaningful benefits in glucose tolerance.

Association between physical function and various patterns of physical activity in older adults: a cross-sectional analysis.

BACKGROUND: To improve physical function, physical activity (PA) guidelines for older adults recommend completing PA in bouts of 10 min or more. Spontaneous PA (< 10 min) can also benefit older adults. However, a paucity of research exists examining if shorter bouts of PA are associated with greater physical function. AIM: To determine the association between various patterns of PA and the likelihood of greater physical function in older adults. METHODS: Older adults from the 2003-2004 and 2005-2006 cycles of the National Health and Nutrition Examination Survey were included for analysis. PA lasting 1, 5, 10, 30, and 60 min was quantified using accelerometers. Physical function was assessed using a Likert scale reflecting the self-reported capability to complete 11 tasks. A single function score was then computed using factor analysis. Logistic regression analyses calculated the association between PA bout length and the likelihood of above average function. RESULTS: PA performed in 1-min (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.01-1.03), 5-min (OR 1.02; CI 1.01-1.03), or 10-min bouts (OR 1.02; CI 1.01-1.03) was associated with greater physical function following adjustment for confounders. When scaled to represent an accumulation of 10 min of MVPA, likelihoods increased for both 1-min ([OR] 1.25; 95% [CI] 1.11-1.39) and 5-min (OR 1.22; 95% CI 1.08-1.37) bouts. DISCUSSION/CONCLUSIONS: Our findings suggest bouts of PA lasting 10 min or shorter in duration are associated with greater physical function in older adults.

Increasing aerobic exercise intensity fails to consistently improve the glycemic response in people living with prediabetes or type 2 diabetes mellitus: the INTENSITY trial.

Some individuals with prediabetes or type 2 diabetes mellitus (T2DM) who engage in exercise will not experience the anticipated improvements in glycemic control, referred to as non-responders. Increasing exercise intensity may improve the proportion of individuals who become responders. The objectives were to (i) identify responders and non-responders based on changes in glycated hemoglobin (HbA1c) in individuals with prediabetes or T2DM following 16 weeks of aerobic exercise; (ii) investigate if increasing exercise intensity enhances the responders' status for individuals not previously responding favourably to the intervention. Participants (n = 40; age = 58.0 years (52.0-66.0); HbA1c = 7.0% (6.0-7.2)) engaged in a two-phase, randomized study design. During phase one, participants performed 16 weeks of treadmill-based, supervised, aerobic exercise at 4.5 metabolic equivalents (METs) for 150 min per week. Thereafter, participants were categorized as responders, non-responders, or unclear based on the 90% confidence interval above, below, or crossing a 0.3% reduction in HbA1c. For phase two, participants were randomized to a maintained intensity (4.5 METs) or increased intensity (6.0 METs) group for 12 weeks. Following phase one, two (4.1%) participants were categorized as responders, four (8.2%) as non-responders, and 43 (87.7%) as unclear. Following phase two, two from the increased intensity group and one from the maintained intensity group experienced an improvement in response categorization. There were no significant between or within group (maintained vs. increased) differences in HbA1c. For most people with prediabetes or T2DM, increasing exercise intensity by 1.5 METs does not improve response categorization.

Does type 2 diabetes duration influence the effectiveness of an aerobic exercise intervention: Results from the INTENSITY study.

BACKGROUND: Studies suggest that longer durations of T2DM increase the risk of T2DM complications and premature mortality. However, whether T2DM duration impacts the efficacy of an aerobic exercise intervention is unclear. OBJECTIVE: The purpose of this study was: 1) to compare changes in body composition, cardiorespiratory fitness, and glycemia between individuals with short- and long-duration T2DM after aerobic exercise and 2) to determine whether these changes were associated with changes in glycemia by T2DM duration. METHODS: A secondary analysis of the INTENSITY study (NCT03787836), including thirty-four adults (≥19 years) with T2DM who participated in 28 weeks of aerobic exercise training for 150 minutes per week at a moderate-to-vigorous intensity (4.5 to 6.0 metabolic equivalents (METs)). Using pre-established cut-points, participants were categorized into two groups 1) short-duration T2DM (<5 years) or 2) long-duration T2DM (≥5 years). Glycemia was measured by glycated hemoglobin (HbA1c), body composition by BodPod, and cardiorespiratory fitness by a measure of peak oxygen consumption (VO2peak). All measurements were performed at baseline, 16 weeks, and 28 weeks. RESULTS: Participants in the short-duration T2DM group experienced decreases in fat mass (kg) (p = 0.03), HbA1c (p = 0.05), and an increased relative VO2peak (p = 0.01). Those with long-duration T2DM experienced decreases in fat mass (kg) (p = 0.02) and HbA1c (p <0.001) and increased fat-free mass (p = 0.02). No significant differences were observed between groups in any outcomes. Changes in fat mass (r = 0.54, p = 0.02), and body fat percentage (r = 0.50, p = 0.02) were significantly associated with the change in HbA1c in those with a long-duration T2DM only. CONCLUSION: Our results suggest T2DM duration did not differently impact the efficacy of a 28-week aerobic exercise intervention. However, changes in body composition were associated with better glycemia in individuals with longer T2DM duration only.

A Comprehensive Analysis of Skin Cancer Concerns and Protective Practices in Manitoba, Canada, Highlights Lack of Skin Cancer Awareness and Predominance of High-Risk Sun Exposure Behaviors.

The rapidly increasing skin cancer rates in Canada are alarming, with current data estimating that 1/3 of Canadians will be affected in their lifetime. Thus, deeper understanding of high-risk sun exposure behaviors is needed to help counter this trend. Only limited action has been taken by federal/provincial governments to reduce skin cancer incidence. A cross-sectional survey study was conducted in Manitoba, with frequency counts, means, and percentages used to encapsulate responses. Age- and gender-adjusted odds ratios were calculated using logistic regression analyses. Our study identified worrying inadequacies in sun protective behaviors and attitudes, with the threat of such high-risk behaviors amplified by a lack of skin cancer awareness. Alarming elements were noted in participants' sun exposure history (>65% reported a history of sunburns, >50% previously used a tanning bed, and >75% recently tanned for pleasure), beliefs and attitudes (>50% believe that they look better/healthier with a tan, and >40% believe that having a base tan is protective against further sun damage), and sun protection efforts (sun protective clothing was used <60% of the time, sunscreen was used by <50%, and there was a lack of knowledge about sunscreen characteristics in ~30% of respondents), in addition to significant differences being established between demographic subgroups (based on gender, age, skin phototype, income, and education attained). This study provides worrisome insight onto the grim landscape of sun protective behaviors and attitudes in Manitoba, which will inevitably translate into higher skin cancer rates and should serve as a call to action to promote targeted public health messaging in this jurisdiction and beyond.

Can non-responders be 'rescued' by increasing exercise intensity? A quasi-experimental trial of individual responses among humans living with pre-diabetes or type 2 diabetes mellitus in Canada.

INTRODUCTION: Exercise is recommended to improve glycaemic control. Yet, individual changes in glycaemic control following exercise can vary greatly, meaning while some significantly improve others, coined 'non-responders', do not. Increasing the intensity of exercise may 'rescue' non-responders and help generate a response to training. This trial will identify non-responders to changes in glycated haemoglobin (HbA1c) across inactive individuals living with pre-diabetes or type 2 diabetes mellitus following an aerobic exercise programme and evaluate if increasing training intensity will elicit beneficial changes to 'rescue' previously categorised non-responders. METHODS AND ANALYSIS: This study will recruit 60 participants for a two-phase aerobic exercise training programme. Participants will be allocated to a control group or assigned to an intervention group. Control participants will maintain their current lifestyle habits. During phase 1, intervention participants will complete 16 weeks of aerobic exercise at an intensity of 4.5 metabolic equivalents (METs) for 150 min per week. Participants will then be categorised as responders or non-responders based on the change in HbA1c. For phase 2, participants will be blocked based on responder status and randomly allocated to a maintained intensity, or increased intensity group for 12 weeks. The maintained group will continue to train at 4.5 METs, while the increased intensity group will train at 6.0 METs for 150 min per week. ETHICS AND DISSEMINATION: Results will be presented at scientific meetings and submitted to peer-reviewed journals. Publications and presentations related to the study will be authorised and reviewed by all investigators. Findings from this study will be used to provide support for future randomised control trials. All experimental procedures have been approved by the Research Ethics Board at the University of New Brunswick (REB: 2018-168). TRIAL REGISTRATION NUMBER: NCT03787836.

Interindividual variation in cardiometabolic health outcomes following 6 months of endurance training in youth at risk of type 2 diabetes mellitus.

This study determined the interindividual variation in the cardiometabolic response to 6 months of moderate or vigorous intensity exercise training (ET) among youth at risk for type 2 diabetes mellitus. Youth were randomized to moderate intensity ET (45-55% heart rate reserve; n = 31), vigorous intensity ET (70-85% heart rate reserve; n = 37), or control (n = 36). Only those attending ≥70% of ET sessions were included. Cardiometabolic measures included insulin sensitivity, hepatic triglyceride content, visceral adipose area, and cardiorespiratory fitness. The contribution of ET to interindividual variation was determined using the standard deviation of individual responses (SDIR) and considered meaningful if the SDIR surpassed the smallest worthwhile difference (SWD), calculated as 0.2 × the standard deviation of the control group baseline values. ET meaningfully contributed to the interindividual variation among changes in peak oxygen uptake following moderate (SDIR: 2.04) and vigorous (SDIR: 3.43) ET (SWD: 1.17 mL·kg fat free mass-1·min-1), body fat percentage and hepatic triglyceride content following moderate-intensity ET (SDIR: 1.64, SWD: 1.05%; SDIR: 10.08, SWD: 1.06%, respectively), and visceral fat mass following vigorous ET (SDIR: 11.06, SWD: 7.13 cm2). Variation in the changes in insulin sensitivity were not influenced by ET. The contribution of ET to interindividual variation appears to be influenced by the desired outcome and prescribed intensity. Trial registration at ClinicalTrials.gov (identifier no.: NCT00755547). Novelty: The contribution of exercise to interindividual variation following training depends on the outcome and exercise intensity. Increasing exercise intensity does not systematically reduce non-response among youth at risk for type 2 diabetes.

Concussions in Community-Level Rugby: Risk, Knowledge, and Attitudes.

BACKGROUND: Rugby is a popular collision sport where participants are at risk of sustaining concussions. Most research focuses on elite-level or youth divisions. Comparatively, little is known about adult community rugby. The aim of this research was to estimate the risk of sustaining a concussion during participation in community-level rugby and summarize the collective knowledge and attitudes toward concussions. HYPOTHESIS: Concussion symptoms will be reported frequently among community-level rugby players and a substantial proportion will report a willingness to continue participation despite the risk. STUDY DESIGN: Cross-sectional analysis. LEVEL OF EVIDENCE: Level 3. METHODS: An anonymous, voluntary survey was administered to all 464 senior rugby players registered in the province of Manitoba in 2015. Two primary domains were assessed: (1) concussion history from the preceding season including occurrence, symptomatology, and impact on daily activities and (2) knowledge and attitudes toward concussion risks and management. RESULTS: In total, 284 (61.2%) rugby players responded. Concussive symptoms were reported by 106 (37.3%). Of those, 87% were formally diagnosed with a concussion and 27% missed school and/or work as a result. The danger of playing while symptomatic was recognized by 93.7% of participants, yet 29% indicated they would continue while symptomatic. Furthermore, 39% felt they were letting others down if they stopped playing due to a concussion. CONCLUSION: Concussive symptoms were common among the study cohort and had a notable impact on daily activities. A high proportion of players were willing to continue while experiencing symptoms despite recognizing the danger. The observed discord between knowledge and attitudes implicates a culture of "playing injured." CLINICAL RELEVANCE: Understanding the risk of injury may affect an individual's decision to participate in community-level rugby. Moreover, evidence of discord between the knowledge and attitudes of players may direct future research initiatives and league governance.