Independent of exercise dose and fat loss, short-term training improves glucose tolerance in relation to enhanced postprandial fuel use.

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.

Individuals with prediabetes who are overweight and obese are at an increased risk of developing endocrine disruption of fat tissue, known as adiposopathy. While short-term exercise improves adipokine profiles, the effects of exercise intensity when matched for energy expenditure on adiposopathy are unknown. We hypothesized that high-intensity exercise would elicit greater changes in adiposopathy compared to moderate exercise. Twenty-eight overweight and obese adults (age: 60.9 ± 8.4 years; BMI: 33.0 ± 5.4 kg m −2 ) with prediabetes were randomized to twelve 60-min sessions of either moderate-continuous (CONT; n = 14) or high-intensity interval (INT; n = 14) exercise training. Total and high molecular weight (HMW) adiponectin and leptin were collected to assess adiposopathy (ratio of total adiponectin to leptin; A/L). Insulin sensitivity (SI IS ) was determined using a 75 g oral glucose tolerance test before and after training.Cardiometabolic risk factors were measured and a z-score was calculated to determine metabolic syndrome (MetS) severity. CONT and INT increased A/L (P < 0.01) and decreased leptin (P < 0.01) and MetS severity (P = 0.04). Neither intervention altered circulating levels of HMW adiponectin (P = 0.76) and only INT increased total adiponectin levels (P = 0.02). Both intensities increased insulin sensitivity (P < 0.01), which was associated with improvements in A/L (r = 0.47, P = 0.01).Additionally, increases in A/L tended to relate to decreased MetS severity (r = −0.36, P = 0.09).Short-term exercise intensity, when matched for energy expenditure, does not differentially affect improvements in adiposopathy in overweight and obese adults with prediabetes. Further, 12 bouts of exercise improved insulin sensitivity and MetS severity, suggesting that improving adipokine profiles may aid in reducing cardiometabolic risk. K E Y W O R D Sadiponectin, leptin, prediabetes 1 632wileyonlinelibrary.com/journal/eph Experimental Physiology. 2020;105:632-640.

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 (V̇normalO2) 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 V̇normalO2) and body mass were also assessed. Short‐term training had no effect on weight but did improve peak V̇normalO2 (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 V̇normalO2 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.

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 (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, VO 2peak: 15.4 ± 0.6 mL/kg/min, BMI: 34.1 ± 1.7 kg/m2) and PF (n = 13, VO 2peak: 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 VO 2peak (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.

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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.