On average, starting an exercise training program decreases one's risk for chronic disease. However, there is remarkable individual variability in physiologic responses to exercise training. The activity and inactivity during the remaining 95% of the day (when the individual is not training) is rarely considered. The overall objective of this dissertation was to apply validated sedentary behavior (SB) and physical activity (PA) measurement techniques during an exercise training study to determine if time spent in SB and PA outside of training influences the physiological response to training. Twenty subjects participated in a pilot study to determine the feasibility of reducing SB and the validity of PA monitors for measuring SB compared to direct observation (DO). Participants completed a 1-week baseline period and a 1-week intervention period, where they were instructed to decrease SB. The correlation between the AP and DO was R2=0.94 and the AG100 and DO sedentary minutes was R2=0.39. SB significantly decreased from 67% of wear time (baseline period) to 62.7% of wear time (intervention period) according to AP. Only the AP was able to detect reductions in SB and was more precise than the AG. Study Two was a 12-week randomized controlled study. There were 4-groups that were instructed to: (1) CON: maintain habitual PA and SB (2) rST: reduce and break-up SB and increase daily steps (3) EX: exercise 5-days per week for 40-minutes per session at moderate intensity (4) EX-rST: combination of EX and rST. Cardiovascular disease risk factors were assessed pre-and post-intervention. The AP was used to verify AP between-group differences in activity at four time-points. EX-rST had improvements in insulin action variables that EX did not. All other physiologic responses to training were similar between EX groups and rST has less robust changes than either EX group. These data provide validation of activity monitors for measuring SB and present preliminary evidence that activity outside of exercise training may influence the metabolic response to training. This dissertation shows that what is done outside of exercise training can and should be quantified using objective monitors that assess daily exposure to activity and inactivity behavior.

There is limited knowledge of the dose-response relationship between physical activity (PA), sedentary behavior (SB) and health. Poor measures of free-living PA and SB exposure are major contributing factors to these knowledge gaps. The overall objective of this dissertation was to address these issues by refining, validating and applying a machine-learning methodology for measuring PA and SB for use in free-living people. By combining neural networks and decision tree analyses we developed a method better suited for use in free-living people. Our new method is called the sojourn method and it estimates PA and SB from a single hip mounted accelerometer. Study 1 validated two versions of this method: sojourn-1x (soj-1x) and sojourn-3x (soj-3x). Soj-1x uses data from a vertical accelerometer sensor, while soj-3x uses r data from the vertical, anterior-posterior and medial-lateral accelerometer sensors. Seven participants were directly observed in the free-living environment for ten consecutive hours on three separate occasions. PA and SB estimated from soj-1x, soj-3x and a neural network previously calibrated in the laboratory (lab-nnet) were compared to direct observation. Compared to the lab-nnet, soj-1x and soj-3x improved estimates of MET-hours (lab-nnet: bias (95% CI) = 5.4 (4.6-6.2), rMSE = 5.4 (4.6-6.2), soj-1x: bias = 0.3 (-0.2-0.9), rMSE = 1.0 (0.6-1.3), soj-3x: bias = 0.5 (-0.1-1.1), rMSE = 1.1 (0.7-1.5)) and minutes in different intensity categories (lab-nnet: rMSE range = 10.2 (vigorous) - 55.0 (light), soj-1x: rMSE range = 4.0 (MVPA) - 50.1 (sedentary), soj-3x: rMSE range = 7.8 (MVPA) - 27.8 (light)). Soj-1x and soj-3x also produced accurate estimates of qualifying minutes, qualifying bouts, breaks from sedentary time and break-rate. Study 2 evaluated the sensitivity of soj-1x and soj-3x to detect change in habitual activity. Thirteen participants completed three, seven day conditions: sedentary, moderately active and very active. Soj-1x and soj-3x were sensitive to change in MET-hours (mean (95% CI): soj-1x: sedentary = 19.8 (19.0-20.7), moderately active = 22.7 (22.0-23.4), very active = 27.0 (25.8-28.2), soj-3x: sedentary = 18.2 (17.7-18.8), moderately active = 22.3 (21.6-23.1), very active = 27.6 (26.4-28.7)) and time in different intensity categories. Study 3 applied soj-3x to a free-living intervention to elucidate the effects of increased sedentary behavior on markers of cardiometabolic health. Eleven participants completed seven days of an active condition followed by seven days of an inactive condition. Insulin action significantly decreased 17% (5.4-30.2), while total cholesterol, LDL and HDL did not change from the active to inactive condition. This dissertation used novel methods to improve PA and SB estimation in a free-living environment and to improve our understanding of the physiologic response to increased free-living SB. These methods ultimately have the potential to broaden our understanding of how PA and SB dose are linked to health.

Skeletal muscle weakness is a problem for people living with Multiple Sclerosis (MS). Alterations in the central nervous system may be the primary source of muscle weakness because of the pathophysiology of MS. However, changes in peripheral mediators of force production may also contribute to muscle weakness in persons with MS. The main objective of the dissertation was to systematically identify key neural (motor unit discharge rates, spasticity) and muscular (muscle size, contractile function) mechanisms of force production that may explain lower isometric strength and dynamic power in persons with MS compared with age-matched controls. The knee extensor muscles of the weaker leg were studied, because this muscle group is commonly affected by MS. We showed that persons with MS had lower peak isometric torque and dynamic power compared with controls. Persons with MS had lower motor unit discharge rates, smaller muscle size, and lower specific power compared with controls. There was no difference in passive torque (spasticity), specific strength, or maximal rate of force development between groups. Because differences in isometric strength between persons with MS and controls were abolished when torque was normalized to muscle size, smaller muscle size may explain a large portion of lower isometric strength in persons with MS. Differences in dynamic power were reduced when peak power was normalized to muscle size, but remained lower in persons with MS compared with controls, suggesting that changes in neural factors (e.g., lower motor unit discharge rates) may explain lower dynamic power in persons with MS. These results suggest that different mechanisms may contribute to muscle weakness in MS, depending on the mode of contraction. Lower motor unit discharge rates and smaller muscle size were identified as key mechanisms of muscle weakness in persons with MS. Each of these mechanisms has been shown to improve with resistance training in controls. Thus, this dissertation provides an evidence-based rationale for resistance training interventions in persons with MS, to improve isometric strength and power production by increasing motor unit discharge rates and muscle size.

abstract: Background: Effective glucose management using exercise modalities in older patients with type 2 diabetes and activities of daily living (ADL) disabilities are unknown. Purpose: The study investigated the acute effects of motor-assisted cycling and functional electrical stimulation (FES) cycling on the 2-h postprandial glucose responses compared with sitting control in older adults with type 2 diabetes and ADL disabilities. Methods: The study used a 3×3 crossover study design. Nine participants were randomly assigned to one of the three treatment sequences: ABC, BCA, and CAB. (A, motor-assisted cycling; B, FES cycling; C, sitting control). Linear mixed models (LMM) with Bonferroni post-hoc tests were used to test the mean differences for the 2-h postprandial glucose, estimated by the area under the curve (AUC) and incremental AUC (iAUC), between intervention and control treatments after adjustment for covariates (e.g., age, sex, and race). Results: There were significant mean differences for iAUC (p = 0.005) and AUC (p = 0.038) across motor-assisted cycling, control, and FES cycling treatments. The FES cycling had a lower mean of 2-hour postprandial iAUC as compared with sitting control (iAUC 3.98 mmol∙h/L vs 6.92 mmol∙h/L, p = 0.006, effect size [ES] = 1.72) and the motor-assisted cycling (iAUC, 3.98 mmol∙h/L vs 6.19 mmol∙h/L , p = 0.0368, ES = 1.29), respectively. The FES cycling also had a lower mean of the 2-hour postprandial AUC as compared with sitting control (AUC, 18.29 mmol∙h/L vs 20.95 mmol∙h/L, p = 0.043, ES = 0.89), but had an AUC similar to the motor-assisted cycling (18.29 mmol∙h/L vs 20.23 mmol∙h/L , p = 0.183, ES = 0.19). There were no statistical differences in iAUC (6.19 mmol∙h/L vs 6.92 mmol∙h/L) and AUC (20.23 mmol∙h/L vs 20.95 mmol∙h/L) between the motor-assisted cycling and sitting control (all p>0.05). Conclusion: Performing 30 minutes of FES cycling on a motor-assisted bike (40 Hz, 39 rpm, 25-29 mA) significantly decreased the 2-h postprandial glucose levels in older adults with type 2 diabetes and ADL disabilities. These findings suggested that FES cycling can be a promising exercise modality for glucose management in diabetic patients with ADL disabilities. / Dissertation/Thesis / Doctoral Dissertation Physical Activity, Nutrition and Wellness 2019

Background: Athletes regularly compete in temperatures ranging from well below 0° Celsius (C) to those exceeding human body temperature (37°C). The lack of current understanding regarding the individual and interactive influences of exercise during hot and cold exposure is currently limiting optimization of training, racing and fueling strategies implemented by endurance athletes when performing in these extreme environments. As such, determining the degree to which ambient temperature affects substrate metabolism and performance both during and after endurance exercise in trained athletes is warranted. In the present study, we systematically investigated the environmental impact of temperature on substrate mobilization within subcutaneous abdominal adipose tissue (SCAAT) in situ and whole-body substrate oxidation during submaximal steady state cycling. Purpose: To investigate the effect of hot, cold, and neutral environmental temperatures on lipolysis within SCAAT and whole-body substrate oxidation during steady state exercise and subsequent time trial (TT) performance in endurance-trained cyclists. Methods: Ten healthy, endurance-trained male cyclists (age = 22.80 ± 2.76 yr; height = 178.58 ± 5.65 cm; mass = 74.02 ± 10.95 kg; body fat = 18.35 ± 3.37%; peak oxygen consumption (VO2peak) = 60.60 ± 4.67 ml·kg-1·min-1; power output at lactate threshold (LT) = 234.00 ± 35.00 W) participated in randomized, crossover design study that consisted of baseline testing to determine LT and VO2peak, two familiarization trials, and three experimental trials. The three experimental trials consisted of cycling in hot (39.03±1.06°C; 40.19±2.18%RH), cold (3.06±1.78°C; 41.63±5.60%RH) and thermoneutral (19.43±0.98°C; 38.97±2.23%RH) temperatures in a randomized order. The exercise protocol consisted of 25 min of cycling at 70% LT, followed immediately by 25 min at 90%LT, a 15-min break and then a 20-km TT in a thermoneutral room. In situ lipolysis of the SCAAT was measured throughout the trial with microdialysis, a minimally invasive method used to monitor SCAAT interstitial glycerol concentrations. Whole-body carbohydrate and fat metabolism was measured via indirect calorimetry, fingerstick and venous blood sampling. Results: Nine out of ten subjects were unable to complete the hot condition steady state portion of the protocol, so no TT was performed on the hot visit. No significant differences (p ≤ 0.05) were observed between groups for any measured variable aside from increased heart rate (HR) in the heat (141.16 ± 2.40 bpm) as compared to cold (124.48 ± 2.40 bpm; p < 0.001) and neutral (127.98 ± 2.40 bpm; p = 0.002) conditions. A significant time effect was observed for HR, core temperature, interstitial glycerol, blood lactate, carbohydrate and fat oxidation, VO2 and RER. No differences were observed between cold and neutral TT performances. Conclusion: SCAAT lipolysis increases during steady state exercise; however, the environmental conditions in which exercise was performed did not significantly alter SCAAT metabolism or blood flow, nor did temperature influence whole-body substrate metabolism in well-trained male cyclists. Subjects were unable to complete the TT in the heat, and no differences were observed between cold and neutral TT performance. / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2016. / June 30, 2016. / Includes bibliographical references. / Michael J. Ormsbee, Professor Directing Dissertation; Robert J. Contreras, University Representative; Lynn B. Panton, Committee Member; Jeong-Su Kim, Committee Member.

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