Postprandial augmentation index is reduced in adults with prediabetes following continuous and interval exercise training.

NEW FINDINGS: What is the central question of this study? We compared high-intensity interval versus continuous training on fasting and postprandial arterial stiffness in people with prediabetes. What is the main finding and its importance? We show, for the first time, that exercise improves the augmentation index during the postprandial state, but not the fasted state, in adults with prediabetes. However, the fasted augmentation index improved in relationship to exercise dose, as assessed by kilocalories per session. Collectively, these findings suggest that short-term exercise can improve arterial compliance in adults with prediabetes. Therefore, lifestyle interventions designed to reduce arterial stiffness could have considerable clinical impact. ABSTRACT: People with prediabetes have elevated risk for cardiovascular disease, in part, owing to arterial stiffness mediated by low insulin sensitivity. However, the effect the intensity and/or amount (i.e. kilocalories per session) of short-term exercise training on fasting and postprandial arterial stiffness is unknown. We tested the hypothesis that increased intensity and dose (i.e. amount) of exercise would be correlated with reduced fasting and postprandial arterial stiffness in obese adults with prediabetes. After randomization, 31 adults (age 61.4 ± 8.3 years, body mass index 32.1 ± 5.4 kg m-2 ) with prediabetes performed supervised continuous (CONT; n = 17; 70% of peak heart rate) or interval (INT; n = 14; 3 min at 50% of peak heart rate and 3 min at 90% of peak heart rate) cycling training for 60 min day-1 over 2 weeks. The amount of exercise was calculated using regression equations derived from oxygen uptake ( V ̇ O 2 ) and heart rate. Arterial stiffness [augmentation index (AI) and cartoid-femoral pulse wave velocity], insulin and glucose were determined during a 180 min 75 g oral glucose tolerance test (OGTT) and analysed by the total area under the curve (tAUC) pre- versus post-training. The simple index of insulin sensitivity, (SIIS )OGTT, was calculated; aerobic fitness (peak V ̇ O 2 ) and body mass were also assessed. Short-term training had no effect on weight but did improve peak V ̇ O 2 (P = 0.003), glucose tAUC180min (P = 0.01) and insulin sensitivity (P = 0.002), independent of intensity. The CONT and INT exercise significantly reduced AI 2 h postprandial (P = 0.008) and tAUC180min (P = 0.03). Reductions in fasted AI were related to exercise dose (trend: r = -0.37, P = 0.055). Increased peak V ̇ O 2 was linked to reduced fasted (r = -0.47, P = 0.01) and tAUC180min AI (r = -0.39, P = 0.05). Decreased AI tAUC180min was correlated with increased insulin sensitivity (r = -0.50, P = 0.009). Short-term CONT and INT training reduced postprandial arterial stiffness comparably in adults with prediabetes.

Two Weeks of Interval Training Enhances Fat Oxidation during Exercise in Obese Adults with Prediabetes.

Prediabetes is associated with impaired oxidative capacity and altered substrate utilization during exercise. The effects of continuous (CONT) versus interval (INT) exercise training on fat oxidation during an acute exercise bout at the same absolute and relative intensities are unknown in this population. Obese females/males (n = 17, n = 5) with prediabetes (BMI 32.2 ± 1.2 kg·m-2; age 62.8 ± 1.6 y; fasting glucose 103.4 ± 1.6 mg·dL-1; 2-hour glucose 153.7 ± 7.1 mg·dL-1; VO2peak 19.9 ± 1.0 mL·kg-1·min-1) were screened with a 75g OGTT. Subjects completed a peak oxygen consumption test and a submaximal exercise substrate utilization test consisting of 5min stages at absolute (30W) and relative (70%HRpeak) intensities before and after randomization to 12 sessions (60min each) of CONT (70% HRpeak) or INT (alternating 3min 90% HRpeak, 3min 50% HRpeak) over a two-week period. Body mass decreased and VO2peak increased more after INT than CONT (INT: -0.6 ± 0.2 kg, CONT: -0.1 ± 0.2 kg; p = 0.04; INT: 1.9 ± 0.6 mL/kg/min, CONT: 0.1 ± 0.6 mL·kg-1·min-1; p = 0.04). Training increased fat oxidation by 0.7 ± 0.2 mL·kg-1·min-1 during the absolute intensity test (p < 0.001), independent of intensity. During the relative intensity test, fat oxidation increased more after INT than CONT (INT: 1.3 ± 0.4 mL·kg-1·min-1, CONT: 0.3 ± 0.3 mL·kg-1·min-1; p = 0.03), with no difference in exercise energy expenditure between groups. Enhanced fat oxidation during the relative test was correlated with increased VO2peak (r = 0.53 p = 0.01). High intensity INT training enhances fat oxidation during the same relative intensity exercise in people with prediabetes.

Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study.

BACKGROUND: Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep. OBJECTIVE: We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion. METHODS: Using data from a cross-sectional sample of participants (n = 129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants' sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean±SD time difference between PSG data collection and MRI data collection was 1.7±1.5 years (range: [0, 4.9 years]). RESULTS: OSA severity was associated with reduced total GM volume (ß=-0.064; SE = 0.023; p = 0.007), greater total WM lesion volume (interaction p = 0.023), and greater WMHs (interaction p = 0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps < 0.05). CONCLUSION: This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.

Insulin Homeostasis Mediates the Relationship Between Cardiorespiratory Fitness and Cognitive Speed in Aging Adults.

BACKGROUND: Cardiorespiratory fitness (CRF) supports cognition, though it is unclear what mechanisms underly this relationship. Insulin resistance adversely affects cognition but can be reduced with habitual exercise. OBJECTIVE: We investigated whether insulin resistance statistically mediates the relationship between CRF and cognition. METHODS: In our observational study, we included n = 1,131 cognitively unimpaired, nondiabetic older adults from a cohort characterized by elevated Alzheimer's disease (AD) risk. We estimated CRF (eCRF) using a validated equation that takes age, sex, body mass index, resting heart rate, and habitual physical activity as inputs. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) quantified insulin resistance. Standardized cognitive factor scores for cognitive speed/flexibility, working memory, verbal learning/memory, and immediate memory were calculated from a battery of neuropsychological tests. Linear regression models and bootstrapped estimates of indirect effects were used to determine whether HOMA-IR mediated significant relationships between eCRF and cognition. RESULTS: eCRF was positively associated with cognitive speed/flexibility (p = 0.034). When controlling for HOMA-IR, eCRF was no longer associated with cognitive speed/flexibility (p = 0.383). HOMA-IR had a significant indirect effect on the eCRF-cognition relationship (B = 0.025, CI = [0.003,0.051]). eCRF was not associated with working memory (p = 0.236), immediate memory (p = 0.345), or verbal learning/memory (p = 0.650). CONCLUSION: Among older adults at risk for AD, peripheral insulin resistance mediates the relationship between CRF and cognitive speed.

Five-year changes in objectively measured cardiorespiratory fitness, physical activity, and sedentary time in mid-to-late adulthood.

This study examined 5-year changes in cardiorespiratory fitness, physical activity, and sedentary time in mid-to-late aged adults. Fifty-seven participants completed baseline and follow-up treadmill exercise tests and physical activity monitoring. We observed a 14% decline in fitness (p < 0.001), 12% decrease in physical activity (p = 0.010), and non-significant increase in sedentary time (p = 0.196). Age was negatively associated with 5-year change in physical activity (r = -0.31; p = 0.02) and this decline was strongest among APOE ε4 carriers (g = -0.75). Novelty: Cardiorespiratory fitness and physical activity significantly declined from mid-to-late adulthood, these findings were most pronounced among older adults and those with genetic risk for Alzheimer's disease.

Impact of a short-term low calorie diet alone or with interval exercise on quality of life and oxidized phospholipids in obese females.

The objective of this study was to test if a low-calorie diet plus interval exercise (LCD+INT) reduced oxidized and non-oxidized phospholipids in relation to improved weight-related quality of life (QoL) to a greater extent than an energy-deficit matched LCD in obese females. Subjects (age: 47.2 ± 2.6 years, body mass index: 37.5 ± 1.3 kg/m2) were randomized to a 13-day LCD (n = 12; mixed meals of ∼1200 kcal/day) or LCD+INT (n = 13; 12 sessions of 60 min/day alternating 3 min at 50% and 90% peak heart rate plus an additional 350 kcal shake fed after exercise to match energy availability between groups). Weight-related QoL (Laval Questionnaire) as well as oxidized (POVPC, HOOA-PC, HPETE-PC, HETE-PC, PEIPC, KOOA-PC) and non-oxidized (PAPC and lysoPC) phospholipids were assessed pre- and post-intervention. Fitness (VO2peak), body composition (BodPod), and clinical bloods were also tested. LCD+INT significantly increased VO2peak (mL/kg/min, P = 0.03) compared to LCD despite similar fat loss, blood glucose, insulin sensitivity, and inflammatory responses. LCD+INT had significantly greater increases in QoL sexual life domain (P = 0.05) and tended to have a greater increase in the emotions domain (P = 0.09) and total score (P = 0.10) compared to LCD. There were no significant differences between treatments for changes in phospholipids despite LCD+INT increasing measured oxidized and non-oxidized phospholipids while LCD decreased POVPC, HOOA-PC, and PEIPC as well as non-oxidized PAPC and lysoPC. Interestingly, the rise in PEIPC correlated with elevated VO2peak (mL/kg/min r = 0.42, P = 0.05). Decreased caloric intake was, however, linked to a decrease in PAPC (r = 0.53, P = 0.01), lysoPC (r = 0.52, P = 0.02), POVPC (r = 0.43, P = 0.05), and HPETE-PC (r = 0.43, P = 0.05). The decrease in HETE-PC also correlated with increases in the QoL domains symptoms (r = -0.46, P = 0.04), hygiene/clothing (r = -0.53, P = 0.01), emotions (r = -0.53, P = 0.01), social interactions (r = -0.49, P = 0.02), and total score (r = -0.52, P = 0.02). In conclusion, although LCD and LCD+INT improved weight related QoL over 13 days in females with obesity, LCD+INT tended to improve sexual life, emotions as well as total QoL score more than LCD. These data suggest caloric restriction and fitness may act through different mechanisms to support QoL.

Circulating Klotho Is Higher in Cerebrospinal Fluid than Serum and Elevated Among KLOTHO Heterozygotes in a Cohort with Risk for Alzheimer's Disease.

BACKGROUND: Klotho is a longevity and neuroprotective hormone encoded by the KLOTHO gene, and heterozygosity for the KL-VS variant confers a protective effect against neurodegenerative disease. OBJECTIVE: Test whether klotho concentrations in serum or cerebrospinal fluid (CSF) vary as a function of KLOTHO KL-VS genotype, determine whether circulating klotho concentrations from serum and CSF differ from one another, and evaluate whether klotho levels are associated with Alzheimer's disease risk factors. METHODS: Circulating klotho was measured in serum (n = 1,116) and CSF (n = 183) of cognitively intact participants (aged 62.4 ± 6.5 years; 69.5% female). KLOTHO KL-VS zygosity (non-carrier; heterozygote; homozygote) was also determined. Linear regression was used to test whether klotho hormone concentration varied as a function of KL-VS genotype, specimen source, and demographic and clinical characteristics. RESULTS: Serum and CSF klotho were higher in KL-VS carriers than non-carriers. Klotho concentration was higher in CSF than in serum. Females had higher serum and CSF klotho, while younger age was associated with higher klotho in CSF. CONCLUSION: In a cohort enriched for risk for Alzheimer's disease, heterozygotic and homozygotic carriers of the KL-VS allele, females, and younger individuals have higher circulating klotho. Fluid source, KL-VS genotype, age, and sex should be considered in analyses of circulating klotho on brain health.

Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease.

Increasing evidence indicates that physical activity and exercise training may delay or prevent the onset of Alzheimer's disease (AD). However, systemic biomarkers that can measure exercise effects on brain function and that link to relevant metabolic responses are lacking. To begin to address this issue, we utilized blood samples of 23 asymptomatic late middle-aged adults, with familial and genetic risk for AD (mean age 65 years old, 50% female) who underwent 26 weeks of supervised treadmill training. Systemic biomarkers implicated in learning and memory, including the myokine Cathepsin B (CTSB), brain-derived neurotrophic factor (BDNF), and klotho, as well as metabolomics were evaluated. Here we show that aerobic exercise training increases plasma CTSB and that changes in CTSB, but not BDNF or klotho, correlate with cognitive performance. BDNF levels decreased with exercise training. Klotho levels were unchanged by training, but closely associated with change in VO2peak. Metabolomic analysis revealed increased levels of polyunsaturated free fatty acids (PUFAs), reductions in ceramides, sphingo- and phospholipids, as well as changes in gut microbiome metabolites and redox homeostasis, with exercise. Multiple metabolites (~30%) correlated with changes in BDNF, but not CSTB or klotho. The positive association between CTSB and cognition, and the modulation of lipid metabolites implicated in dementia, support the beneficial effects of exercise training on brain function. Overall, our analyses indicate metabolic regulation of exercise-induced plasma BDNF changes and provide evidence that CTSB is a marker of cognitive changes in late middle-aged adults at risk for dementia.

Effect of presurgical aerobic exercise on cardiometabolic health 30 days after bariatric surgery.

We evaluated the effect of preoperative standard medical care (SC) vs. unsupervised aerobic exercise combined with SC (EX + SC) on cardiometabolic health and quality of life (QoL) 30 days after bariatric surgery. Bariatric patients (n = 14, age: 42.3 ± 2.5 years, body mass index: 45.1 ± 2.5 kg/m2 ) were match-paired to presurgical SC (n = 7) or EX + SC (n = 7; walking 30 min/day, 5 day/week, 65-85% HRpeak ) for 30 days. Body composition, peak cardiorespiratory fitness (VO2 peak), QoL, inflammation (adiponectin, leptin, cytokeratin-18), and a 120 min mixed meal tolerance test was performed to assess aortic waveforms (augmentation index, AIx@75), insulin sensitivity, and glucose total area under the curve (tAUC) at the time of surgery (post-intervention) and 30 days post-surgery. EX + SC had significantly higher high molecular weight (HMW) adiponectin (p = 0.01) and ratio of HMW to total adiponectin (p = 0.04) than SC at 30 days post-surgery, although they significantly (p = 0.006; ES = 1.86) decreased total time spent in moderate to vigorous physical activity (MVPA). SC had a significantly greater increase in VO2 peak (p = 0.02; ES = 1.54) and decrease in 120 min AIx@75 (p = 0.02; ES = 1.78) than EX + SC during the post-surgical period. The increase in MVPA was associated with a reduction in cytokeratin-18 (r = -0.67, p = 0.02). Increased VO2 peak was associated with increased activity/mobility QoL domain (r = 0.52, p = 0.05) and decreased 120 min AIx@75 (r = -0.61, p = 0.03) from surgery to post-surgery. Preoperative EX + SC did not maintain more favorable cardiometabolic health 30 days post-operation in this pilot study. However, changes in MVPA appear important for QoL and should be considered in future work.

Cardiorespiratory fitness mitigates brain atrophy and cognitive decline in adults at risk for Alzheimer's disease.

INTRODUCTION: Cardiorespiratory fitness (CRF) may mitigate Alzheimer's disease (AD) progression. This study examined the longitudinal associations of CRF with brain atrophy and cognitive decline in a late-middle-aged cohort of adults at risk for AD. METHODS: One hundred ten cognitively unimpaired adults (66% female, mean age at baseline 64.2 ± 5.7 years) completed a baseline graded treadmill exercise test, two brain magnetic resonance imaging scans (over 4.67 ± 1.17 years), and two to three cognitive assessments (over 3.26 ± 1.02 years). Linear mixed effects models examined the longitudinal associations adjusted for covariates. RESULTS: Participants with higher baseline CRF had slower annual decline in total gray matter volume (P = .013) and cognitive function (P = .048), but not hippocampal volume (P = .426). Exploratory analyses suggested these effects may be stronger among apolipoprotein E ε4 carriers. DISCUSSION: CRF is a modifiable physiological attribute that may be targeted during the preclinical phase of AD in effort to delay disease progression, perhaps most effectively among those with genetic risk.

Pre-operative aerobic exercise on metabolic health and surgical outcomes in patients receiving bariatric surgery: A pilot trial.

OBJECTIVE: Examine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes. METHODS: Fourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65-85% HRpeak) for 30d. A 120min mixed meal tolerance test was performed pre- and post-intervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO2peak), body composition (BodPod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen's d effect size (ES) was used to test group differences. RESULTS: SC tended to increase percent body fat (P = 0.06) after the intervention compared to EX+SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO2peak 2.9% compared to a 5.9% decrease with SC (P = 0.24, ES = 0.91). This increased fitness correlated to shorter operating time (r = -0.57, P = 0.03) and length of stay (r = -0.58, P = 0.03). Less omental total adiponectin (r = 0.52, P = 0.09) and leptin (r = 0.58, P = 0.05) expression correlated with shorter operating time, and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01), and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01). CONCLUSION: Adding pre-operative aerobic exercise to standard care may improve surgical outcomes through a fitness and adipose tissue derived mechanism.

Protocol of Aerobic Exercise and Cognitive Health (REACH): A Pilot Study.

A growing body of evidence supports that aerobic exercise can decrease the risk of future cognitive impairment and Alzheimer's disease (AD). There is a pressing need to rigorously determine whether cognitively normal yet at-risk individuals stand to benefit from the protective effects of exercise. The present study will test the feasibility of an aerobic exercise intervention in such a population and inform the design of a larger-scale randomized, controlled trial examining the effect of aerobic exercise on biomarkers of AD in late-middle-aged, at-risk individuals. This was a single-site, 1 : 1 block-randomized, parallel, two-arm trial. Cognitively normal participants aged 45-80 with documentation of familial and genetic AD risk factors were randomly assigned to one of two interventions. The Usual Physical Activity group was provided educational materials about exercise. The Enhanced Physical Activity intervention delivered 26 weeks of individualized and supervised aerobic exercise. Exercise duration and intensity were incrementally increased to 150 min/week and 70-80% of heart rate reserve, respectively. Retention and adherence were measured to assess study feasibility. In addition, pre- and post- intervention differences between the two arms were evaluated for cardiorespiratory fitness, physical activity, brain glucose metabolism, cerebral structure, vascular health, memory, executive function, and mood. Data from randomized controlled trials of exercise training are needed to identify the proper exercise prescription for reducing accumulation of AD biomarkers in cognitively normal individuals. The current trial will contribute to filling that gap while informing the design of large-scale trials.

Two weeks of exercise training intensity on appetite regulation in obese adults with prediabetes.

No short-term exercise data exist testing whether training intensity modifies hormonal and perceived appetite in obese adults with prediabetes. Therefore, we compared the effects of short-term moderate-continuous (CONT) vs. high-intensity interval (INT) training on appetite regulation. Twenty-eight obese adults [age: 61.3 ± 1.5 yr; body mass index (BMI): 33.2 ± 1.1 kg/m2] with prediabetes were randomized to work-matched CONT ( n = 14) or INT ( n = 14) training for 2 wk. Plasma acylated ghrelin (AG), des-acylated ghrelin (dAG), active glucagon-like peptide-1 (GLP-1), and insulin were measured at 0, 30, and 60 min of a 75-g oral glucose tolerance test (OGTT) before and after training. Visual analog scales were administered at 0 and 120 min during the OGTT to examine perceived appetite. Three-day food logs were collected before and after testing to assess ad libitum diet. CONT and INT increased peak oxygen consumption ( P < 0.01) and decreased BMI ( P < 0.01). Although neither intervention altered fasting levels of AG ( P = 0.94), dAG ( P = 0.36), or insulin ( P = 0.67), CONT raised GLP-1 compared with INT ( P = 0.05). Exercise training did not affect postprandial suppression of AG ( P = 0.81) and dAG ( P = 0.67) or stimulation of GLP-1 ( P = 0.67) and insulin ( P = 0.32). Both interventions tended to decrease total energy and protein intake ( P = 0.09 and P = 0.05, respectively), despite no change in fasting hunger ( P = 0.88) and reduced perceived fullness at 120 min during the OGTT ( P = 0.05). We conclude that 2 wk of exercise training intensity does not modulate appetite-regulatory hormones in obese adults with prediabetes. Although perceived fullness to the OGTT was reduced after exercise, CONT and INT decreased energy intake, suggesting that exercise does not elicit compensatory appetite behavior to gain weight. NEW & NOTEWORTHY Adults with prediabetes are at risk for appetite dysregulation. Although exercise promotes weight management, it is unclear whether moderate-continuous or high-intensity interval training is more beneficial for appetite regulation. We show that 2 wk of exercise, independent of intensity, does not alter postprandial appetite hormones or hunger, despite slight reductions in food intake and weight. These data support exercise as an effective method to induce negative energy balance without compensatory weight gain.

Brain Glucose Metabolism, Cognition, and Cardiorespiratory Fitness Following Exercise Training in Adults at Risk for Alzheimer's Disease.

Aerobic exercise has been associated with reduced burden of brain and cognitive changes related to Alzheimer's disease (AD). However, it is unknown whether exercise training in asymptomatic individuals harboring risk for AD improves outcomes associated with AD. We investigated the effect of 26 weeks of supervised aerobic treadmill exercise training on brain glucose metabolism and cognition among 23 late-middle-aged adults from a cohort enriched with familial and genetic risk of AD. They were randomized to Usual Physical Activity (PA) or Enhanced PA conditions. Usual PA received instruction about maintaining an active lifestyle. Enhanced PA completed a progressive exercise training program consisting of 3 sessions of treadmill walking per week for 26 weeks. By week seven, participants exercised at 70- 80% heart rate reserve for 50 minutes per session to achieve 150 minutes of moderate intensity activity per week in accordance with public health guidelines. Before and after the intervention, participants completed a graded treadmill test to assess VO2peak as a measure of cardiorespiratory fitness (CRF), wore an accelerometer to measure free-living PA, underwent 18F-fluorodeoxyglucose positron emission tomography imaging to assess brain glucose metabolism, and a neuropsychological battery to assess episodic memory and executive function. VO2peak increased, sedentary behavior decreased, and moderate-to-vigorous PA increased significantly in the Enhanced PA group as compared to Usual PA. Glucose metabolism in the posterior cingulate cortex (PCC) did not change significantly in Enhanced PA relative to Usual PA. However, change in PCC glucose metabolism correlated positively with change in VO2peak. Executive function, but not episodic memory, was significantly improved after Enhanced PA relative to Usual PA. Improvement in executive function correlated with increased VO2peak. Favorable CRF adaptation after 26 weeks of aerobic exercise training was associated with improvements in PCC glucose metabolism and executive function, important markers of AD.

A low-calorie diet with or without interval exercise training improves adiposopathy in obese women.

The objective of this study was to test if a low-calorie diet plus interval exercise (LCD+INT) improves adiposopathy, an endocrine dysfunction, when compared with an energy-deficit-matched LCD in obese women. Subjects (age: 48.2 ± 2.4 years, body mass index: 37.8 ± 1.3 kg/m2) were randomized to a 13-day LCD (n = 12; mixed meals of ∼1200 kcal/day) or LCD+INT (n = 12; 12 sessions of 60 min/day alternating 3 min at 50% and 90% peak heart rate). Exercise was estimated to expend 350 kcal per oxygen uptake-heart rate regression analysis and individuals were refed calories expended to match energy availability between groups. Absolute (post - pre caloric intake) and relative (total daily and exercise energy expenditure relative to calorie intake) energy deficits were calculated. Fitness (peak oxygen uptake) and body composition (BodPod; Cosmed USA Inc.) were measured and a 120-min, 75g oral glucose tolerance test was performed at pre- and post-intervention to assess adiposopathy (i.e., ratio of high molecular weight-adiponectin to leptin) and estimate insulin sensitivity. LCD and LCD+INT had similar absolute (P = 0.55) and relative (P = 0.76) energy deficits. LCD and LCD+INT had similar reductions in fat mass (both P < 0.001), despite LCD inducing greater weight loss (P = 0.02) than LCD+INT. Both treatments improved adiposopathy (P = 0.003) and peripheral insulin sensitivity (P = 0.02). Absolute energy deficit correlated to improved adiposopathy (r = -0.41, P = 0.05), and absolute and relative energy deficits were associated with increased insulin sensitivity (r = -0.47, P = 0.02; and r = -0.40, P = 0.05, respectively), independent of body composition changes and increased peak oxygen uptake. Taken together, LCD, with or without INT, improves adiposopathy in relation to insulin sensitivity in obese women, suggesting that a short-term energy deficit is key for reducing risk of type 2 diabetes.

Low cardiorespiratory fitness is associated with higher extracellular vesicle counts in obese adults.

Low cardiorespiratory fitness (CRF) is associated with cardiovascular disease (CVD) independent of obesity. Extracellular vesicles (EVs) are a novel target of CVD, however, it remains unknown if obese individuals with very poor fitness (VPF) have elevated EVs versus people with poor fitness (PF). Thus, we tested whether VPF was associated with greater EV subtypes in obese adults. Subjects with VPF (n = 13, VO2 peak: 15.4 ± 0.6 mL/kg/min, BMI: 34.1 ± 1.7 kg/m2 ) and PF (n = 13, VO2 peak: 25.9 ± 3.0 mL/kg/min, BMI: 32.1 ± 1.2 kg/m2 ) were compared in this cross-sectional study. After an overnight fast, AnnexinV (AV) +/- platelet (CD31+ /CD41+ ), leukocyte (CD45+ /CD41- ), and endothelial EVs (CD105+ , CD31+ /CD41- ) were analyzed from fresh platelet poor plasma via imaging flow cytometry. Body fat, blood pressure (BP), and glucose tolerance (OGTT) were also tested. Body weight, BP, and circulating glucose were similar between groups, although VPF subjects were older than PF (64.0 ± 2.1 vs. 49.8 ± 4.2 year; P < 0.05). People with VPF, compared with PF, had higher total AV- EVs (P = 0.04), AV- platelet EVs (CD31+ /CD41+ ; P = 0.006), and AV- endothelial EVs (CD31+ /CD41- ; P = 0.005) independent of age and body fat. Higher AV- platelet and endothelial EVs were associated with lower VO2 peak (r = -0.56, P = 0.006 and r = -0.55, P = 0.005, respectively). Endothelial-derived AV- /CD31+ /CD41- EVs were also related to pulse pressure (r = 0.45, P = 0.03), whereas AV- /CD105 was linked to postprandial glucose (r = 0.41, P = 0.04). VPF is associated with higher AnnexinV- total, endothelial, and platelet EVs in obese adults, suggesting that subtle differences in fitness may reduce type 2 diabetes and CVD risk through an EV-related mechanism.

Glucose Tolerance is Linked to Postprandial Fuel Use Independent of Exercise Dose.

PURPOSE: The optimal short-term exercise dose to improve glucose tolerance in relation to metabolic flexibility and/or insulin resistance is unknown. Therefore, we tested if short-term, work-matched continuous (CONT) versus interval (INT) exercise training improves glucose tolerance in part by reducing insulin resistance and increasing metabolic flexibility independent of clinically meaningful fat loss in adults with prediabetes. METHODS: Subjects (age = 60.9 ± 1.4 yr, body mass index = 33.5 ± 1.1 kg·m) were screened for prediabetes using the American Diabetes Association criteria (75 g oral glucose tolerance test [OGTT] and/or HbA1c) and were randomized to 60 min·d of supervised CONT (n = 17, 70% HRpeak) or work-matched INT (n = 14; 90% HRpeak for 3 min and 50% HRpeak for 3 min) exercise for 12 bouts. Fitness (V˙O2peak) and body composition were assessed pre- and postintervention. A 180-min 75-g OGTT was performed, and glucose, insulin, and free fatty acids were collected to calculate glucose tolerance (tAUC180min) and whole-body as well as adipose tissue insulin resistance pre- and postintervention. RER (indirect calorimetry) was also measured at 0, 60, 120, and 180 min of the OGTT to assess fasting and postprandial metabolic flexibility. RESULTS: CONT and INT training improved V˙O2peak (L·min; P = 0.001) and glucose tolerance (P = 0.01) and reduced fasting RER (P = 0.006), as well as whole-body and adipose insulin resistance (both P = 0.02) with no effect on body fat (P = 0.18). Increased postprandial RER was correlated with reduced glucose tAUC180min (r = -0.38, P = 0.05) and increased 180-min RER related to decreased whole-body insulin resistance (r = -0.42, P = 0.03). CONCLUSION: Independent of exercise dose and fat loss, short-term training improves glucose tolerance in relation to enhanced postprandial fuel use.

Enhancing Exercise Responsiveness across Prediabetes Phenotypes by Targeting Insulin Sensitivity with Nutrition.

Exercise is a cornerstone therapy for chronic diseases related to multiorgan insulin resistance. However, not all individuals show the anticipated improvement in insulin sensitivity following exercise and these individuals are considered exercise resistant. Caloric restriction is an approach to enhance the effect of exercise on increasing peripheral and hepatic insulin sensitivity, as replenishing expended calories blunts these benefits. Alternatively, restricting carbohydrate intake, independent of energy balance, following exercise provides an additive effect on peripheral insulin sensitivity when compared to refeeding carbohydrate. Although carbohydrate composition modulates insulin sensitivity, few have studied effects of low glycemic index or whole-grain diets following exercise across prediabetes phenotypes on insulin sensitivity. Herein, we propose the novel hypothesis that the combination of individualized nutrition therapy and exercise should be based on the clinical pathology of prediabetes to overcome exercise resistance and improve responsiveness in people at risk for type 2 diabetes and cardiovascular disease.