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.

Factors that predict compliance in a virtual cardiac rehabilitation program.

BACKGROUND: Despite the well-established benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), participation in CR remain low. Virtual CR programs present a unique opportunity to promote utilization. To date, few virtual CR cohorts have been analyzed for compliance. This study aims to determine factors that predict compliance within a large virtual CR program in the United States. METHODS: We analyzed 1409 patients enrolled in the Kaiser Permanente Mid-Atlantic States Virtual CR program that consists of 12 CR sessions via telephone. Demographic characteristics, as well as body weight, blood pressure, HbA1c level, and smoking status were collected at admission. Patients were further classified by CVD diagnosis codes. Compliance was defined as at least 75% (9/12 sessions) attendance. Data was analyzed using simple and multiple regression models with significance defined as P < 0.05. RESULTS: Age was the single strongest predictor for virtual CR compliance (adjusted R2 = 0.58; P < 0.001), and non-compliant patients were younger. HbA1C level, CVD diagnosis codes, and smoking status each moderately predicted compliance (adjusted R2 = 0.48, 0.42, and 0.31, respectively; P < 0.001). Smoking and HbA1C level combined in a multiple regression model significantly improved prediction of compliance (adjusted R2 = 0.79, P < 0.01). Sex, baseline weight or hypertension were not significant predictors of CR compliance. CONCLUSIONS: Age, diabetes, CVD diagnoses, smoking status at admission are independent predictors of compliance in a large virtual CR program. Targeted intervention could be designed accordingly to improve CR compliance.

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.

A Low-Calorie Diet with or without Exercise Reduces Postprandial Aortic Waveform in Females with Obesity.

PURPOSE: Arterial stiffness is considered a predictor of cardiovascular disease. Females have higher values of arterial stiffness than males, suggesting a greater risk of heart-related complications. Although a low-calorie diet (LCD) reduces fasting arterial stiffness, in part through weight loss, it is unknown if interval exercise (INT) adds to the benefit of LCD on fasting and postprandial arterial stiffness in females with obesity. METHODS: Twenty-five females (47 ± 2.6 yr, 37.6 ± 1.3 kg·m-2) were randomized to 13 d of LCD (n = 12; mixed meals of ~1200 kcal·d-1) or LCD + INT (n = 13; 60 min·d-1 of supervised 3-min intervals at 90% HRpeak and 50% HRpeak). Arterial stiffness (augmentation index [AIx] and carotid-femoral pulse wave velocity [cfPWV]) and blood biochemistries were measured during a 75-g oral glucose tolerance test before and after the intervention to determine fasting and postprandial arterial stiffness as well as insulin sensitivity (simple index of insulin sensitivity [SIIS]) and inflammation (C-reactive protein, interleukin 8, and tumor necrosis factor alpha). RESULTS: Although LCD + INT increased V˙O2peak and HDL compared with LCD (P = 0.04 and P < 0.01, respectively), both interventions decreased body fat, LDL, total cholesterol, and triglycerides (all P < 0.01) and increased SIIS (P = 0.03). Despite no effect on fasting AIx (P = 0.27), LCD and LCD + INT decreased AIx60min (-7.4% ± 4.3% vs -7.0% ± 5.0%, P = 0.04) and tAUC120min (-663 ± 263 vs -457 ± 406, P = 0.03). There were no changes in fasting cfPWV (P = 0.91) or cfPWV120min (P = 0.62). Increased SIIS and decreased interleukin 8 were associated with reduced fasting AIx (r = -0.44, P = 0.03, and r = 0.40, P = 0.055), whereas decreased C-reactive protein correlated with reduced postprandial AIx60min (r = 0.43, P = 0.04). CONCLUSION: Independent of exercise, 13 d of LCD reduces postprandial AIx in females with obesity. Insulin sensitivity and inflammation correlated with improved arterial stiffness, suggesting unique mechanisms regulate fasted versus postprandial arterial stiffness.

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.

Short-term interval exercise suppresses acylated ghrelin and hunger during caloric restriction in women with obesity.

Caloric restriction is suggested to increase hunger, in part, through complex interactions of hormones and behavior that contribute to challenges in long-term weight loss. Although intense exercise may attenuate appetite, no data exist testing the effects of interval exercise (INT) during a low-calorie diet (LCD) on appetite regulation. We hypothesized that LCD+INT would favorably influence satiety when compared with an energy-deficit matched LCD in women with obesity. Twenty-six women with obesity (47.3±2.4 yrs; 37.3 ± 1.2 kg/m2) were randomized to either LCD (n = 13; mixed meals of ~1200 kcal/d) or LCD+INT (n = 13; 60 min/d of supervised interval exercise at 90% HRpeak for 3 min and 50% HRpeak for 3 min) for 2 weeks. An additional 350kcal (shake) was provided to LCD+INT individuals post-exercise to equate energy availability between groups. Total PYY, acylated ghrelin and des-ghrelin were measured at 0, 30 and 60 min of a 75g OGTT before and after the intervention. Visual analog scales were also administered at 0 and 120 min of the OGTT to assess appetite perception. Food logs were recorded prior to and during the intervention to ensure caloric intake compliance. Compared with pre-intervention conditions, both interventions decreased food intake (P = 0.001) and body fat (P < 0.01). There was no effect on fasting PYY, but both LCD and LCD+INT increased post-prandial PYY iAUC (P < 0.001) relative to pre-intervention. LCD+INT maintained fasting acylated ghrelin (P = 0.06) and suppressed post-prandial acylated ghrelin iAUC (P = 0.04) compared to LCD. Neither intervention impacted circulating des- ghrelin before or following the OGTT. Interestingly, LCD+INT attenuated fasting hunger and maintained fullness compared with LCD (P = 0.05 and P = 0.06, respectively). Taken together, interval exercise favors acylated ghrelin suppression and perception of hunger during a LCD in women with obesity.

Interval Exercise Lowers Circulating CD105 Extracellular Vesicles in Prediabetes.

BACKGROUND: Extracellular vesicles (EV) are purported to mediate type 2 diabetes and CVD risk and development. Physical activity and a balanced diet reduce disease risk, but no study has tested the hypothesis that short-term interval (INT) training would reduce EV compared with continuous (CONT) exercise in adults with prediabetes. METHODS: Eighteen obese adults (age, 63.8 ± 1.5 yr; body mass index, 31.0 ± 1.3 kg·m) were screened for prediabetes using American Diabetes Association criteria (75 g oral glucose tolerance test). Subjects were randomized to INT (n = 10, alternating 3-min intervals at 90% and 50% HRpeak, respectively) or CONT (n = 8, 70% HRpeak) training for 12 supervised sessions over 13 d for 60 min·d. Cardiorespiratory fitness (V˙ O2peak), weight (kg), as well as ad libitum dietary intake were assessed and arterial stiffness (augmentation index via applanation tonometry) was calculated using total AUC during a 75-g oral glucose tolerance test performed 24 h after the last exercise bout. Total EV, platelet EV (CD31/CD41), endothelial EV (CD105; CD31/ CD41), platelet endothelial cell adhesion molecule (PECAM) (CD31), and leukocyte EV (CD45; CD45/CD41) were analyzed via imaging flow cytometry preintervention/postintervention. RESULTS: The INT exercise increased V˙O2peak (P = 0.04) compared with CONT training. Although training had no effect on platelet or leukocyte EV, INT decreased Annexin V- endothelial EV CD105 compared with CONT (P = 0.04). However, after accounting for dietary sugar intake, the intensity effect was lost (P = 0.18). Increased ad libitum dietary sugar intake after training was linked to elevated AV+ CD105 (r = 0.49, P = 0.06) and AV- CD45 (r = 0.59, P = 0.01). Nonetheless, increased V˙O2peak correlated with decreased AV+ CD105 (r = -0.60, P = 0.01). CONCLUSIONS: Interval exercise training decreases endothelial-derived EV in adults with prediabetes. Although increased sugar consumption may alter EV after a short-term exercise intervention, fitness modifies EV count.

Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery.

OBJECTIVE: Examine the effect of aerobic exercise (EX) combined with standard medical care (SC) (EX + SC) compared to SC alone on cardiometabolic health and quality of life in relation to surgical outcomes. METHODS: Patients receiving bariatric surgery were match-paired to 30 days of pre-operative SC (n = 7, 1 male, 39.0 ± 5.3 years, body mass index 46.4 ± 3.0 kg/m2; low calorie diet) or EX + SC (n = 7, 0 males, 45.6 ± 4.8 years, body mass index 43.9 ± 4.2 kg/m2; walking 30 min/day, 5 days/week, 65-85% HR peak ). Body mass, waist circumference, cardiorespiratory fitness (VO2peak), high sensitivity C-reactive protein (hs-CRP), cytokeratin 18 (CK18), weight related quality of life (QoL), and a 120 min mixed meal tolerance test (MMTT) was performed to assess arterial stiffness via augmentation index normalized to a heart rate of 75 beats per minute (AIx@75), whole-body insulin sensitivity, and glucose total area under the curve (tAUC) pre- and post-intervention (∼2 days prior to surgery). Length of hospital stay (admission to discharge) was recorded. RESULTS: EX + SC had a greater effect for decreased intake of total calories (P = 0.14; ES = 0.86) compared to SC, but no change in body weight or waist circumference was observed in either group. EX + SC had a greater effect for increased VO2peak (P = 0.24; ES = 0.91) and decreased hs-CRP (P = 0.31; ES = 0.69) compared to SC. EX + SC reduced circulating CK18 (P = 0.05; ES = 3.05) and improved QoL (P = 0.02) compared to SC. Although EX + SC had no statistical effect on arterial stiffness compared to SC, we observed a modest effect size for AIx@75 tAUC (P = 0.36; ES = 0.52). EX + SC had a significantly shorter length of hospital stay (P = 0.05; ES = 1.38) than SC, and a shorter length of hospital stay was associated with decreased sugar intake (r = 0.55, P = 0.04). Decreased AIx@75 tAUC significantly correlated with improved whole-body insulin sensitivity (r = -0.59, P = 0.03) and glucose tAUC (r = 0.57, P = 0.04). CONCLUSION: EX with SC for 30 days prior to bariatric surgery may be important for cardiometabolic health, quality of life, and surgical outcomes in the bariatric patient.

Endothelial function following interval exercise plus low-calorie diet treatment in obese females.

We determined if interval exercise plus a low-calorie diet (LCD + INT) increases endothelial function more than an energy-matched LCD. Obese women (47.2 ± 2.6y, 37.5 ± 1.3kg/m2 ) were randomized to 13 days of a LCD (n = 12; mixed meals of ~ 1200kcal/d) or LCD + INT (n = 13; 12 supervised 60-min INT bouts of 3 min at 90% and 50% HRpeak ). LCD + INT subjects received 350kcal postexercise to equate energy availability with LCD. Fitness (VO2 peak) and body composition (BodPod) were determined and a 120 min, 75 g oral glucose tolerance test was performed to examine fasting and postprandial flow-mediated dilation (FMD, endothelial function), respiratory exchange ratio (RER) via indirect calorimetry as well as glucose and insulin incremental area under the curve (iAUC120min ). LCD + INT increased VO2 peak (P = 0.02) compared with LCD, and both treatments decreased fat mass (P < 0.001) and insulin iAUC120min (P = 0.03). There was no overall treatment effect on fasting or iAUC120min FMD. However, in participants who increased fasting endothelial function after each treatment (Δ > 50%; LCD n = 5, LCD + INT n = 7), LCD + INT increased fasted (P = 0.005) and decreased iAUC120min (P = 0.003) FMD compared with LCD. Enhanced fitness correlated with increased fasting FMD (r = 0.43, P = 0.03) and diminished FMD iAUC120min (r = -0.44, P = 0.03). Decreased FMD iAUC120min correlated with reduced glucose iAUC120min (r = 0.64, P = 0.001) as well as increased 60-min RER (r = -0.42, P = 0.04). Low baseline fasting and iAUC120min FMD was also linked to enhanced fasting and iAUC120min FMD post-treatment (r = -0.71, P < 0.001; r = -0.89, P < 0.001, respectively). In conclusion, increasing fitness via INT may increase the effect of LCD on lowering cardiovascular disease risk in obese women.

An Oral Glucose Load Decreases Postprandial Extracellular Vesicles in Obese Adults with and without Prediabetes.

Although extracellular vesicles (EVs) are a novel biomediator of type 2 diabetes (T2D) and cardiovascular disease (CVD), the effects of hyperglycemia on EVs in humans is unknown. We tested the hypothesis that a 75-g oral glucose tolerance test (OGTT) would promote changes in EVs in relation to CVD risk. Twenty-five obese adults (Age: 52.4 ± 3.2 year, BMI: 32.5 ± 1.2 kg/m²) were screened for normal glucose tolerance (NGT, n = 8) and prediabetes (PD, n = 17) using American Diabetes Association criteria (75 g OGTT and/or HbA1c). Body composition (bioelectrical impedance) and fitness (VO2peak) were measured. Arterial stiffness (augmentation index; AIx) was measured at 0, 60- and 120-min while insulin, glucose, and free fatty acids were evaluated every 30 min during the OGTT to assess CVD risk. Annexin V positive (AV+) and Annexin V negative (AV-) total EVs, platelet EVs (CD31⁺/CD41⁺; CD41⁺), leukocyte EVs (CD45⁺; CD45⁺/CD41-), platelet endothelial cell adhesion molecule (PECAM) (CD31⁺) and endothelial EVs (CD 31⁺/CD41-; CD105⁺) were collected at 0 and 120 min. There were no differences in age, BMI, or body fat between NGT and PD (all P > 0.63). Total EVs, AV+ CD31+ (PECAM), and AV+ CD31⁺/CD41- (endothelial) EVs decreased after the OGTT (P ≤ 0.04). Circulating insulin at 2-h correlated with elevated post-prandial AV- CD45⁺ (r = 0.48, P = 0.04) while arterial stiffness related to reduced total EVs (r = -0.49, P = 0.03) and AV+CD41⁺ (platelet) (r = -0.52, P = 0.02). An oral glucose load lowers post-prandial total, platelet, and endothelial EVs in obese adults with NGT and prediabetes in relation to CVD risk.

Impact of Short-Term Continuous and Interval Exercise Training on Endothelial Function and Glucose Metabolism in Prediabetes.

INTRODUCTION: The impact of interval (INT) vs. continuous (CONT) exercise training on endothelial function in relation to glucose metabolism prior to clinically meaningful weight loss is unknown in adults with prediabetes. METHODS: Twenty-six subjects with prediabetes (60 ± 1 y; 33 ± 1 kg/m2; 2-hr-PG OGTT: 145 ± 7 mg/dl) were randomized to 60 min of CONT (n = 12; 70% of HRpeak) or work-matched INT exercise training (n = 14; alternating 3 min at 90 and 50% HRpeak) for 2 weeks. Aerobic fitness (VO2peak) and body composition (bioelectrical impedance) were assessed before and after training. Flow-mediated dilation (FMD) was measured during a 2 h 75 g OGTT (0, 60, and 120 min) to assess endothelial function. Postprandial FMD was calculated as incremental area under the curve (iAUC). Glucose tolerance and insulin were also calculated by iAUC. Fasting plasma VCAM, ICAM, and hs-CRP were also assessed as indicators of vascular/systemic inflammation. RESULTS: Both interventions increased VO2peak (P = 0.002) but had no effect on body fat (P = 0.20). Although both treatments improved glucose tolerance (P = 0.06) and insulin iAUC (P = 0.02), VCAM increased (P = 0.01). There was no effect of either treatment on ICAM, hs-CRP, or fasting as well as postprandial FMD. However, 57% of people improved fasting and iAUC FMD following CONT compared with only 42% after INT exercise (each: P = 0.04). Elevated VCAM was linked to blunted fasting FMD after training (r = -0.38, P = 0.05). But, there was no correlation between fasting FMD or postprandial FMD with glucose tolerance (r = 0.17, P = 0.39 and r = 0.02, P = 0.90, respectively) or insulin iAUC following training (r = 0.34, P = 0.08 and r = 0.04, P = 0.83, respectively). CONCLUSION: Endothelial function is not improved consistently after short-term training, despite improvements in glucose and insulin responses to the OGTT in obese adults with prediabetes.

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.

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.

Extracellular Vesicles: A Novel Target for Exercise-Mediated Reductions in Type 2 Diabetes and Cardiovascular Disease Risk.

Regular exercise is important for reducing type 2 diabetes (T2D) and/or cardiovascular disease (CVD) risk. However, only about 40-50% of this CVD risk reduction is accounted for by adiposity, hyperglycemia, hypertension, and dyslipidemia. Herein, we present the novel hypothesis that extracellular vesicles (EVs) are candidate biomarkers that may relate to impaired endothelial function and insulin resistance independent of obesity risk factors. EVs are small membrane-bound particles that are generated by cells following stimulation, stress, or activation. They carry markers of their parent cell and are thought to be potent bioactivators and communicators. We discuss the underlying physiology of specific cell type EVs, as well as examine how acute and chronic exercise interventions impact EV count and phenotype. We also propose that current gaps in the field are in part related to use of different detection techniques and the lack of standardized measurements of EV affecting the pre- and postanalytical phase. Ultimately, improving the understanding of how EVs impact cardiometabolic health and their function will lead to improved approaches for enhancing diagnostic options as well as designing exercise interventions that treat and/or prevent T2D and CVD.

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.

Combining Short-Term Interval Training with Caloric Restriction Improves ß-Cell Function in Obese Adults.

Although low-calorie diets (LCD) improve glucose regulation, it is unclear if interval exercise (INT) is additive. We examined the impact of an LCD versus LCD + INT training on ß-cell function in relation to glucose tolerance in obese adults. Twenty-six adults (Age: 46 ± 12 year; BMI 38 ± 6 kg/m²) were randomized to 2-week of LCD (~1200 kcal/day) or energy-matched LCD + INT (60 min/day alternating 3 min at 90 and 50% HRpeak). A 2 h 75 g oral glucose tolerance test (OGTT) was performed. Insulin secretion rates (ISR) were determined by deconvolution modeling to assess glucose-stimulated insulin secretion ([GSIS: ISR/glucose total area under the curve (tAUC)]) and ß-cell function (Disposition Index [DI: GSIS/IR]) relative to skeletal muscle (Matsuda Index), hepatic (HOMA-IR) and adipose (Adipose-IRfasting) insulin resistance (IR). LCD + INT, but not LCD alone, reduced glucose and total-phase ISR tAUC (Interactions: p = 0.04 and p = 0.05, respectively). Both interventions improved skeletal muscle IR by 16% (p = 0.04) and skeletal muscle and hepatic DI (Time: p < 0.05). Improved skeletal muscle DI was associated with lower glucose tAUC (r = -0.57, p < 0.01). Thus, LCD + INT improved glucose tolerance more than LCD in obese adults, and these findings relate to ß-cell function. These data support LCD + INT for preserving pancreatic function for type 2 diabetes prevention.

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.

Impact of short-term exercise training intensity on ß-cell function in older obese adults with prediabetes.

The effect of work-matched exercise intensity on ß-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased ß-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. ß-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = -0.52, P = 0.002 and r = -0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, ß-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that ß-cell function is a strong predictor of glycemia regardless of exercise intensity.