Reversible Airflow Obstruction Predicts Future Chronic Obstructive Pulmonary Disease Development in the SPIROMICS Cohort: An Observational Cohort Study.

Rationale: Chronic obstructive pulmonary disease (COPD) is defined by fixed spirometric ratio, FEV1/FVC < 0.70 after inhaled bronchodilators. However, the implications of variable obstruction (VO), in which the prebronchodilator FEV1/FVC ratio is less than 0.70 but increases to 0.70 or more after inhaled bronchodilators, have not been determined. Objectives: We explored differences in physiology, exacerbations, and health status in participants with VO compared with reference participants without obstruction. Methods: Data from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort were obtained. Participants with VO were compared with reference participants without obstruction. Measurements and Main Results: We assessed differences in baseline radiographic emphysema and small airway disease at study entry, baseline, and change in lung function by spirometry, functional capacity by 6-minute walk, health status using standard questionnaires, exacerbation rates, and progression to COPD between the two groups. All models were adjusted for participant characteristics, asthma history, and tobacco exposure. We assessed 175 participants with VO and 603 reference participants without obstruction. Participants with VO had 6.2 times the hazard of future development of COPD controlling for other factors (95% confidence interval, 4.6-8.3; P < 0.001). Compared with reference participants, the VO group had significantly lower baseline pre- and post-bronchodilator (BD) FEV1, and greater decline over time in post-BD FEV1, and pre- and post-BD FVC. There were no significant differences in exacerbations between groups. Conclusions: Significant risk for future COPD development exists for those with pre- but not post-BD airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. OBJECTIVE: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. STUDY DESIGN AND METHODS: The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. RESULTS: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). INTERPRETATION: The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

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 (V̇O2) reserve; (2) high/vigorous-16 KKW at 75% V̇O2 reserve; (3) low/moderate-10 KKW at 50% V̇O2 reserve; (4) low/moderate plus diet-10 KKW at 50% V̇O2 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. Analyses of covariance determined differences in change scores among groups (p<0.05). Paired t-tests determined significant pre-intervention versus post-intervention scores within groups (p<0.05). RESULTS: Across the intervention, all groups (p<0.05) improved the physical component, SPF, and SPA scores. Only the low/moderate/diet group (p<0.001) significantly improved the mental component score. The high/vigorous group achieved 84.5% of the low/moderate/diet group effect for change in physical component score, and the low/moderate group achieved 83.7% of the low/moderate/diet group effect for change in mental component score. CONCLUSIONS: In general, a low amount of moderate intensity exercise combined with diet was the most effective intervention for improving HrQoL. Of the exercise-only interventions, vigorous intensity exercise provided the greatest impact on changes in physical function. On the other hand, low amounts of moderate intensity exercise provided the greatest impact on mental well-being, potentially being a more attainable exercise dose for previously sedentary individuals with pre-diabetes to achieve.

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

Background: 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. Methods: In a prospective randomized controlled trial, we studied the effects of 6 months of AT vs. RT in 21 subjects. Testing included cardiac and vascular ultrasoundography and serial CP for ventricular-arterial coupling (Ees/Ea), strain-based variables, brachial artery flow-mediated dilation (BAFMD), and peak VO2 (pVO2; mL/kg/min) and peak O2-pulse (O2p; mL/beat). Results: Within the AT group (n = 11), there were significant increases in rVO2 of 4.2 mL/kg/min (SD 0.93) (p = 0.001); O2p of 1.9 mL/beat (SD 1.3) (p = 0.008) and the brachial artery post-hyperemia peak diameter 0.18 mm (SD 0.08) (p = 0.05). Within the RT group (n = 10) there was a significant increase in left ventricular end diastolic volume 7.0 mL (SD 9.8; p = 0.05) and percent flow-mediated dilation (1.8%) (SD 0.47) (p = 0.004). Comparing the AT and RT groups, post exercise, rVO2 2.97, (SD 1.22), (p = 0.03), O2p 0.01 (SD 1.3), (p = 0.01), peak hyperemic blood flow volume (1.77 mL) (SD 140.69) (p = 0.009), were higher in AT, but LVEDP 115 mL (SD 7.0) (p = 0.05) and Ees/Ea 0.68 mmHg/ml (SD 0.60) p = 0.03 were higher in RT. Discussion: The differential effects of AT and RT in this hypothesis generating study have important implications for exercise modality and clinical endpoints.

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

Purpose: 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. Materials and Methods: Participants (n = 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. The SF-36 survey, Satisfaction with Physical Function and Appearance survey, physical fitness, and anthropometrics were assessed at baseline and post-intervention. Paired t-tests determined significant pre- vs. post-intervention scores within groups (p < 0.05). Analyses of covariance determined differences in change scores among groups (p < 0.05). Results: On average, participants were 49.0 ± 10.6 years old, obese (BMI: 30.6 ± 3.2 kg/m2), female (57.7%), and Caucasian (84.7%). Following the 8-month intervention, exercise groups improved peak VO2 (all groups), strength (RT and AT/RT), and anthropometric measures (AT and AT/RT). For the SF-36, RT (p = 0.03) and AT/RT (p < 0.001) significantly improved their physical component score; only AT/RT (p < 0.001) significantly improved their mental component score. Notably, all groups significantly improved both their satisfaction with physical function and appearance scores (All Groups: p < 0.001 for both outcomes). Conclusions: We found that aerobic, resistance, or combination exercise training improves several components of self-rated HrQoL, including physical function, appearance, and mental well-being. Clinical Trial Registration: No. NCT00275145.

Development of a Workplace Intervention for Child Care Staff: Caring and Reaching for Health's (CARE) Healthy Lifestyles Intervention.

Child care staff are among the lowest wage workers, a group at increased risk for a wide array of chronic diseases. To date, the health of child care staff has been largely ignored, and there have been very few interventions designed for child care staff. This article describes the development of the Caring and Reaching for Health (CARE) Healthy Lifestyles intervention, a workplace intervention aimed at improving physical activity and health behaviors among child care staff. Theory and evidence-based behavior change techniques informed the development of intervention components with targets at multiple social ecological levels. Final intervention components included an educational workshop held at a kick-off event, followed by three 8-week campaigns. Intervention components within each campaign included (1) an informational magazine, (2) goal setting and weekly behavior self-monitoring, (3) weekly tailored feedback, (4) e-mail/text prompts, (5) center-level displays that encouraged team-based goals and activities, and (6) coaching for center directors. This multilevel, theory-driven intervention is currently being evaluated as part of a larger randomized controlled trial. Process evaluation efforts will assess the extent to which child care staff participated in, engaged with, and were satisfied with the intervention. Lessons learned will guide future intervention research engaging child care workers.

Workplace health and safety intervention for child care staff: Rationale, design, and baseline results from the CARE cluster randomized control trial.

BACKGROUND: Low-wage workers suffer disproportionately high rates of chronic disease and are important targets for workplace health and safety interventions. Child care centers offer an ideal opportunity to reach some of the lowest paid workers, but these settings have been ignored in workplace intervention studies. METHODS: Caring and Reaching for Health (CARE) is a cluster-randomized controlled trial evaluating efficacy of a multi-level, workplace-based intervention set in child care centers that promotes physical activity and other health behaviors among staff. Centers are randomized (1:1) into the Healthy Lifestyles (intervention) or the Healthy Finances (attention control) program. Healthy Lifestyles is delivered over six months including a kick-off event and three 8-week health campaigns (magazines, goal setting, behavior monitoring, tailored feedback, prompts, center displays, director coaching). The primary outcome is minutes of moderate and vigorous physical activity (MVPA); secondary outcomes are health behaviors (diet, smoking, sleep, stress), physical assessments (body mass index (BMI), waist circumference, blood pressure, fitness), and workplace supports for health and safety. RESULTS: In total, 56 centers and 553 participants have been recruited and randomized. Participants are predominately female (96.7%) and either Non-Hispanic African American (51.6%) or Non-Hispanic White (36.7%). Most participants (63.4%) are obese. They accumulate 17.4 (±14.2) minutes/day of MVPA and consume 1.3 (±1.4) and 1.3 (±0.8) servings/day of fruits and vegetables, respectively. Also, 14.2% are smokers; they report 6.4 (±1.4) hours/night of sleep; and 34.9% are high risk for depression. CONCLUSIONS: Baseline data demonstrate several serious health risks, confirming the importance of workplace interventions in child care.

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. GlycA, fitness, and body habitus were measured in 169 sedentary adults (45-75 years) with prediabetes randomly assigned to one of four six-month exercise-based lifestyle interventions. Interventions included exercise prescription based on the amount (energy expenditure (kcal/kg weight/week (KKW)) and intensity (%VO2peak). The groups were (1) low-amount/moderate-intensity (10KKW/50%) exercise; (2) high-amount/moderate-intensity (16KKW/50%) exercise; (3) high-amount/vigorous-intensity (16KKW/75%) exercise; and (4) a Clinical Lifestyle (combined diet plus low-amount/moderate-intensity exercise) intervention. Six months of exercise training and/or diet-reduced GlycA (mean Δ: -6.8 ± 29.2 µmol/L; p = 0.006) and increased VO2peak (mean Δ: 1.98 ± 2.6 mL/kg/min; p < 0.001). Further, visceral (mean Δ: -21.1 ± 36.6 cm2) and subcutaneous fat (mean Δ: -24.3 ± 41.0 cm2) were reduced, while liver density (mean Δ: +2.3 ± 6.5HU) increased, all p < 0.001. When including individuals in all four interventions, GlycA reductions were associated with reductions in visceral adiposity (p < 0.03). Exercise-based lifestyle interventions reduced GlycA concentrations through mechanisms related to exercise-induced modulations of visceral adiposity. This trial is registered with Clinical Trial Registration Number NCT00962962.

The Health and Working Conditions of Women Employed in Child Care.

Over one million women are employed in child care and are among the lowest wage workers in the US. The health and working conditions of 674 child care workers (118 administrators and 556 staff) from 74 centers is described using baseline data from a larger intervention trial. Participants were 39.9 (±13.0) years old; 55.4% African American, 37.1% Caucasian, and 5.3% of Hispanic ethnicity. Seventy-six percent reported having an Associate's degree or less; 42% were classified as at or below poverty (<$20,000); and exhibited many health risks such as excess weight, insufficient activity, poor diet, and inadequate sleep. We investigated potential differences by income and job category. Lower income participants were significantly more likely to be current smokers (19.9% vs. 11.7%), drink more sweetened beverages (1.9 vs. 1.5), and report higher depressive symptoms (15.5 vs. 12.6). Administrators worked more hours weekly compared to staff (46.4 vs. 40.6), are less active (100 vs. 126 min/week), more sedentary (501 vs. 477 min/day), and reported higher job demands (13.3 vs. 12.5). Given the numerous health issues and challenging work conditions, we hope our results serve as a call to action for addressing low wages and the work environment as a means of influencing the health and well-being of child care workers.

Does a lack of physical activity explain the rheumatoid arthritis lipid profile?

BACKGROUND: In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile. METHODS: NMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined. RESULTS: Subjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05). CONCLUSIONS: The RA-associated lipoprotein profile is associated with a lack of physical activity. As this was a cross-sectional investigation and not an intervention and was performed from 2008-13, this study was not registered in clinicaltrials.gov.

Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial.

AIMS/HYPOTHESIS: Although the Diabetes Prevention Program (DPP) established lifestyle changes (diet, exercise and weight loss) as the 'gold standard' preventive therapy for diabetes, the relative contribution of exercise alone to the overall utility of the combined diet and exercise effect of DPP is unknown; furthermore, the optimal intensity of exercise for preventing progression to diabetes remains very controversial. To establish clinical efficacy, we undertook a study (2009 to 2013) to determine: how much of the effect on measures of glucose homeostasis of a 6 month programme modelled after the first 6 months of the DPP is due to exercise alone; whether moderate- or vigorous-intensity exercise is better for improving glucose homeostasis; and to what extent amount of exercise is a contributor to improving glucose control. The primary outcome was improvement in fasting plasma glucose, with improvement in plasma glucose AUC response to an OGTT as the major secondary outcome. METHODS: The trial was a parallel clinical trial. Sedentary, non-smokers who were 45-75 year old adults (n = 237) with elevated fasting glucose (5.28-6.94 mmol/l) but without cardiovascular disease, uncontrolled hypertension, or diabetes, from the Durham area, were studied at Duke University. They were randomised into one of four 6 month interventions: (1) low amount (42 kJ kg body weight(-1) week(-1) [KKW])/moderate intensity: equivalent of expending 42 KKW (e.g. walking ∼16 km [8.6 miles] per week) with moderate-intensity (50% [Formula: see text]) exercise; (2) high amount (67 KKW)/moderate intensity: equivalent of expending 67 KKW (∼22.3 km [13.8 miles] per week) with moderate-intensity exercise; (3) high amount (67 KKW)/vigorous intensity: equivalent to group 2, but with vigorous-intensity exercise (75% [Formula: see text]); and (4) diet + 42 KKW moderate intensity: same as group 1 but with diet and weight loss (7%) to mimic the first 6 months of the DPP. Computer-generated randomisation lists were provided by our statistician (G. P. Samsa). The randomisation list was maintained by L. H. Willis and C. A. Slentz with no knowledge of or input into the scheduling, whereas all scheduling was done by L. A. Bateman, with no knowledge of the randomisation list. Subjects were automatically assigned to the next group listed on the randomisation sheet (with no ability to manipulate the list order) on the day that they came in for the OGTT, by L. H. Willis. All plasma analysis was done blinded by the individuals doing the measurements (i.e. lipids, glucose, insulin). Subjects and research staff (other than individuals analysing the blood) were not blinded to the group assignments. RESULTS: Number randomised, completers and number analysed with complete OGTT data for each group were: low-amount/moderate-intensity (61, 43, 35); high-amount/moderate-intensity (61, 44, 40); high-amount/vigorous-intensity (61, 43, 38); diet/exercise (54, 45, 37), respectively. Only the diet and exercise group experienced a decrease in fasting glucose (p < 0.001). The means and 95% CIs for changes in fasting glucose (mmol/l) for each group were: high-amount/moderate-intensity -0.07 (-0.20, 0.06); high-amount/vigorous 0.06 (-0.07, 0.19); low-amount/moderate 0.05 (-0.05, 0.15); and diet/exercise -0.32 (-0.46, -0.18). The effects sizes for each group (in the same order) were: 0.17, 0.15, 0.18 and 0.71, respecively. For glucose tolerance (glucose AUC of OGTT), similar improvements were observed for the diet and exercise (8.2% improvement, effect size 0.73) and the 67 KKW moderate-intensity exercise (6.4% improvement, effect size 0.60) groups; moderate-intensity exercise was significantly more effective than the same amount of vigorous-intensity exercise (p < 0.0207). The equivalent amount of vigorous-intensity exercise alone did not significantly improve glucose tolerance (1.2% improvement, effect size 0.21). Changes in insulin AUC, fasting plasma glucose and insulin did not differ among the exercise groups and were numerically inferior to the diet and exercise group. CONCLUSIONS/INTERPRETATION: In the present clinical efficacy trial we found that a high amount of moderate-intensity exercise alone was very effective at improving oral glucose tolerance despite a relatively modest 2 kg change in body fat mass. These data, combined with numerous published observations of the strong independent relation between postprandial glucose concentrations and prediction of future diabetes, suggest that walking ∼18.2 km (22.3 km prescribed with 81.6% adherence in the 67 KKW moderate-intensity group) per week may be nearly as effective as a more intensive multicomponent approach involving diet, exercise and weight loss for preventing the progression to diabetes in prediabetic individuals. These findings have important implications for the choice of clinical intervention to prevent progression to type 2 diabetes for those at high risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00962962 FUNDING: The study was funded by National Institutes for Health National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NDDK) (R01DK081559).

A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls.

BACKGROUND: RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA. METHODS: Plasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance. RESULTS: On average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1ß, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = -0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all). CONCLUSIONS: GlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.

The impact of short-term depot-medroxyprogesterone acetate treatment on resting metabolic rate.

OBJECTIVE: This study examines the effect of a progestogen (depot-medroxyprogesterone acetate, DMPA) on resting metabolic rate (RMR) in a cohort of young, normal-weight healthy women. We hypothesize an increase in RMR and nonshivering thermogenesis (NST) resulting in increased body temperature by DMPA. STUDY DESIGN: We performed a prospective cohort study in 13 subjects tested at baseline, 3 weeks and 9 weeks after 150 mg intramuscular DMPA administration. RMR was determined with indirect calorimetry. Secondary endpoints included changes in body mass index (BMI), body composition, temperature and serum levels of estradiol (E2), luteinizing hormone (LH), progesterone and MPA. RESULTS: The percent change in RMR from baseline to week 3 (9%) was significantly higher than the percent change from baseline to week 9 (1.6%) (p=.045). The greatest percent change from baseline to week 3 compared to baseline to week 9 was seen in women initiating DMPA in the luteal phase of the cycle. Hypothalamic-pituitary-ovarian axis was evident by decreases in E2, LH and progesterone. DMPA resulted in increased body temperature with a significant correlation between the change in body temperature and the change in RMR. No change in body composition was seen. CONCLUSIONS: RMR and NST increased in young healthy women with normal BMI 3 weeks after receiving the initial dose of 150 mg DMPA for contraception. The effect was augmented when the drug was administered during the luteal phase of the menstrual cycle. IMPLICATION: DMPA increases RMR and thermogenesis independent of changes in body mass. An increase in weight with chronic DMPA may result from a combination of hyperphagia and abnormal NST in predisposed individuals.

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, ß-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

The relationship between the blood pressure responses to exercise following training and detraining periods.

BACKGROUND: Exercise training lowers blood pressure (BP), while BP increases and returns to pre-training values with detraining. Yet, there is considerable variability in these BP responses. We examined the relationship between the BP responses after 6 months of training followed by 2 weeks of detraining among the same people. METHODOLOGY/PRINCIPAL FINDINGS: Subjects (n = 75) (X+SD, 50.2 ± 10.6 yr) were sedentary, obese, and had prehypertension. They completed an aerobic (n = 34); resistance (n = 28); or aerobic + resistance or concurrent (n = 13) exercise training program. We calculated a metabolic syndrome z score (MetSz). Subjects were classified as BP responders (BP decreased) or non-responders (BP increased) to training and detraining. Linear and multivariable regression tested the BP response. Chi Square tested the frequency of responders and non-responders. The systolic BP (SBP, r =  -0.474) and diastolic (DBP, r =  -0.540) response to training negatively correlated with detraining (p<0.01), independent of modality (p>0.05). Exercise responders reduced SBP 11.5 ± 7.8 (n = 29) and DBP 9.8 ± 6.2 mmHg (n = 31); non-responders increased SBP 7.9.± 10.9 (n = 46) and DBP 4.9 ± 7.1 mmHg (n = 44) (p<0.001). We found 65.5% of SBP training responders were SBP detraining non-responders; while 60.9% of SBP training non-responders were SBP detraining responders (p = 0.034). Similarly, 80.6% of DBP training responders were DBP detraining non-responders; while 59.1% of DBP training non-responders were DBP detraining responders (p<0.001). The SBP detraining response (r =  -0.521), resting SBP (r =  -0.444), and MetSz (r = 0.288) explained 44.8% of the SBP training response (p<0.001). The DBP detraining response (r =  -0.553), resting DBP (r =  -0.450), and MetSz (r = 0.463) explained 60.1% of the DBP training response (p<0.001). CONCLUSIONS/SIGNIFICANCE: As expected most subjects that decreased BP after exercise training, increased BP after detraining. An unanticipated finding was most subjects that increased BP after exercise training, decreased BP after detraining. Reasons why the negative effects of exercise training on BP maybe reversed with detraining among some people should be explored further. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov 1R01HL57354; 2003-2008; NCT00275145.

Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.

AIMS/HYPOTHESIS: Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms. METHODS: Subjects at risk of metabolic disease were randomised to 6 months of inactivity or one of five aerobic and/or resistance training programmes (n = 112). Pre/post-intervention assessments included cardiorespiratory fitness ([Formula: see text]), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism. RESULTS: Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of even-chain acylcarnitines (median 37-488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in [Formula: see text], TGs and SI (R = 0.20-0.31, p < 0.05). Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R = 0.39 and 0.24, p < 0.05) emerged as the strongest correlates of SI. CONCLUSIONS/INTERPRETATION: The metabolic signatures of exercise-trained skeletal muscle reflected reprogramming of mitochondrial function and intermediary metabolism and correlated with changes in cardiometabolic fitness. Succinate metabolism and the succinate dehydrogenase complex emerged as a potential regulatory node that intersects with whole-body insulin sensitivity. This study identifies new avenues for mechanistic research aimed at understanding the health benefits of physical activity. Trial registration ClinicalTrials.gov NCT00200993 and NCT00275145 Funding This work was supported by the National Heart, Lung, and Blood Institute (National Institutes of Health), National Institute on Aging (National Institutes of Health) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health).

Adipose depots, not disease-related factors, account for skeletal muscle insulin sensitivity in established and treated rheumatoid arthritis.

OBJECTIVE: In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity. METHODS: Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference. RESULTS: Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SI geometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10(-5) min(-1)/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use. CONCLUSION: In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.

Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults.

Recent guidelines on exercise for weight loss and weight maintenance include resistance training as part of the exercise prescription. Yet few studies have compared the effects of similar amounts of aerobic and resistance training on body mass and fat mass in overweight adults. STRRIDE AT/RT, a randomized trial, compared aerobic training, resistance training, and a combination of the two to determine the optimal mode of exercise for obesity reduction. Participants were 119 sedentary, overweight or obese adults who were randomized to one of three 8-mo exercise protocols: 1) RT: resistance training, 2) AT: aerobic training, and 3) AT/RT: aerobic and resistance training (combination of AT and RT). Primary outcomes included total body mass, fat mass, and lean body mass. The AT and AT/RT groups reduced total body mass and fat mass more than RT (P < 0.05), but they were not different from each other. RT and AT/RT increased lean body mass more than AT (P < 0.05). While requiring double the time commitment, a program of combined AT and RT did not result in significantly more fat mass or body mass reductions over AT alone. Balancing time commitments against health benefits, it appears that AT is the optimal mode of exercise for reducing fat mass and body mass, while a program including RT is needed for increasing lean mass in middle-aged, overweight/obese individuals.

Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT.

While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18-70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130-190 mg/dl or HDL cholesterol ≤ 40 mg/dl for men or ≤ 45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set, 2) AT, which was equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O(2) uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in subcutaneous abdominal fat (P < 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater reduction in liver fat score (P < 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode.

Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT).

Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk factors; however, to our knowledge, no randomized clinical studies have addressed whether resistance training (RT) improves the MS when performed alone or combined with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years completed a 4-month inactive run-in period and were randomized to 1 of 3 eight-month exercise programs (n = 196). The exercise programs were (1) RT (3 days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting all major muscle groups); (2) AT (∼120 minutes/week at 75% of the maximum oxygen uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86 participants with complete data for all 5 MS criteria were used in the present analysis, and a continuous MS z score was calculated. Eight months of RT did not change the MS score. AT improved the MS score (p <0.07) and showed a trend toward significance compared to RT (p <0.10). AT/RT significantly decreased the MS score and was significantly different from RT alone. In conclusion, RT was not effective at improving the MS score; however, AT was effective. Combined AT and RT was similarly effective but not different from AT alone. When weighing the time commitment versus health benefit, the data suggest that AT alone was the most efficient mode of exercise for improving cardiometabolic health.