Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

The effect of repeated hot water immersion on insulin sensitivity, heat shock protein 70, and inflammation in individuals with type 2 diabetes mellitus.

Repeated hot water immersion (HWI) can improve glycemic control in healthy individuals but data are limited for individuals with type 2 diabetes mellitus (T2DM). The present study investigated whether repeated HWI improves insulin sensitivity and inflammatory status and reduces plasma ([extracellular heat shock protein 70]) [eHSP70] and resting metabolic rate (RMR). Fourteen individuals with T2DM participated in this pre- versus postintervention study, with outcome measures assessed in fasted (≥12 h) and postprandial (2-h post-75 g glucose ingestion) states. HWI consisted of 1 h in 40°C water (target rectal temperature 38.5°C-39°C) repeated 8-10 times within a 14-day period. Outcome measures included insulin sensitivity, plasma [glucose], [insulin], [eHSP70], inflammatory markers, RMR, and substrate utilization. The HWI intervention increased fasted insulin sensitivity (QUICKI; P = 0.03) and lowered fasted plasma [insulin] (P = 0.04), but fasting plasma [glucose] (P = 0.83), [eHSP70] (P = 0.08), [IL-6] (P = 0.55), [IL-10] (P = 0.59), postprandial insulin sensitivity (P = 0.19), plasma [glucose] (P = 0.40), and [insulin] (P = 0.47) were not different. RMR was reduced by 6.63% (P < 0.05), although carbohydrate (P = 0.43) and fat oxidation (P = 0.99) rates were unchanged. This study shows that 8-10 HWIs within a 14-day period improved fasting insulin sensitivity and plasma [insulin] in individuals with T2DM, but not when glucose tolerance is challenged. HWI also improves metabolic efficiency (i.e., reduced RMR). Together these results could be clinically important and have implications for metabolic health outcomes and well-being in individuals with T2DM.NEW & NOTEWORTHY This is the first study to investigate repeated HWI to raise deep body temperature on insulin sensitivity, inflammation, eHSP70, and substrate utilization in individuals with T2DM. The principal novel findings were improvements in fasting insulin sensitivity and fasting plasma [insulin] but no change in fasting plasma [glucose], postprandial insulin sensitivity, plasma [insulin], or [glucose]. There was also no change in eHSP70, inflammatory status, or substrate utilization but there were reductions in RMR and oxygen consumption.

Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study.

Previous research has shown that ≤60 min hypoxic exposure improves subsequent glycaemic control, but the optimal level of hypoxia is unknown and data are lacking from individuals with overweight. We undertook a cross-over pilot feasibility study investigating the effect of 60-min prior resting exposure to different inspired oxygen fractions (CON FI O2  = 0.209; HIGH FI O2  = 0.155; VHIGH FI O2  = 0.125) on glycaemic control, insulin sensitivity, and oxidative stress during a subsequent oral glucose tolerance test (OGTT) in males with overweight (mean (SD) BMI = 27.6 (1.3) kg/m2 ; n = 12). Feasibility was defined by exceeding predefined withdrawal criteria for peripheral blood oxygen saturation (SpO2 ), partial pressure of end-tidal oxygen or carbon dioxide and acute mountain sickness (AMS), and dyspnoea symptomology. Hypoxia reduced SpO2 in a stepwise manner (CON = 97(1)%; HIGH = 91(1)%; VHIGH = 81(3)%, p < 0.001), but did not affect peak plasma glucose concentration (CON = 7.5(1.8) mmol∙L-1 ; HIGH = 7.7(1.1) mmol∙L-1 ; VHIGH = 7.7(1.1) mmol∙L-1 ; p = 0.777; η2  = 0.013), plasma glucose area under the curve, insulin sensitivity, or metabolic clearance rate of glucose (p > 0.05). We observed no between-conditions differences in oxidative stress (p > 0.05), but dyspnoea and AMS symptoms increased in VHIGH (p < 0.05), with one participant meeting the withdrawal criteria. Acute HIGH or VHIGH exposure prior to an OGTT does not influence glucose homeostasis in males with overweight, but VHIGH is associated with adverse symptomology and reduced feasibility.

Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study.

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2-3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics-cfPWV, AIx@HR75, and cDBP as well as DBP and MAP-responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2-3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.

The physiological and clinical importance of cardiorespiratory fitness in people with abdominal aortic aneurysm.

NEW FINDINGS: What is the topic of this review? This review focuses on the physiological impact of abdominal aortic aneurysm (AAA) on cardiorespiratory fitness and the negative consequences of low fitness on clinical outcomes in AAA. We also discuss the efficacy of exercise training for improving cardiorespiratory fitness in AAA. What advances does it highlight? We demonstrate the negative impact of low fitness on disease progression and clinical outcomes in AAA. We highlight potential mechanistic determinants of low fitness in AAA and present evidence that exercise training can be an effective treatment strategy for improving cardiorespiratory fitness, postoperative mortality and disease progression. ABSTRACT: An abdominal aortic aneurysm (AAA) is an abnormal enlargement of the aorta, below the level of the renal arteries, where the aorta diameter increases by >50%. As an aneurysm increases in size, there is a progressive increase in the risk of rupture, which ranges from 25 to 40% for aneurysms >5.5 cm in diameter. People with AAA are also at a heightened risk of cardiovascular events and associated mortality. Cardiorespiratory fitness is impaired in people with AAA and is associated with poor (postoperative) clinical outcomes, including increased length of hospital stay and postoperative mortality after open surgical or endovascular AAA repair. Although cardiorespiratory fitness is a well-recognized prognostic marker of cardiovascular health and mortality, it is not assessed routinely, nor is it included in current clinical practice guidelines for the management of people with AAA. In this review, we discuss the physiological impact of AAA on cardiorespiratory fitness, in addition to the consequences of low cardiorespiratory fitness on clinical outcomes in people with AAA. Finally, we summarize current evidence for the effect of exercise training interventions on cardiorespiratory fitness in people with AAA, including the associated improvements in postoperative mortality, AAA growth and cardiovascular risk. Based on this review, we propose that cardiorespiratory fitness should be considered as part of the routine risk assessment and monitoring of people with AAA and that targeting improvements in cardiorespiratory fitness with exercise training might represent a viable adjunct treatment strategy for reducing postoperative mortality and disease progression.

Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case-Control Study.

Macrophages are implicated in the pathogenesis of abdominal aortic aneurysm (AAA). This study examined the environmentally conditioned responses of AAA macrophages to inflammatory stimuli. Plasma- and blood-derived monocytes were separated from the whole blood of patients with AAA (30-45 mm diameter; n = 33) and sex-matched control participants (n = 44). Increased concentrations of pro-inflammatory and pro-oxidant biomarkers were detected in the plasma of AAA patients, consistent with systemic inflammation and oxidative stress. However, in monocyte-derived macrophages, a suppressed cytokine response was observed in AAA compared to the control following stimulation with lipopolysaccharide (LPS) (tumor necrosis factor alpha (TNF-α) 26.9 ± 3.3 vs. 15.5 ± 3.2 ng/mL, p < 0.05; IL-6 3.2 ± 0.6 vs. 1.4 ± 0.3 ng/mL, p < 0.01). LPS-stimulated production of 8-isoprostane, a biomarker of oxidative stress, was also markedly lower in AAA compared to control participants. These findings are consistent with developed tolerance in human AAA macrophages. As Toll-like receptor 4 (TLR4) has been implicated in tolerance, macrophages were examined for changes in TLR4 expression and distribution. Although TLR4 mRNA and protein expression were unaltered in AAA, cytosolic internalization of receptors and lipid rafts was found. These findings suggest the inflamed, pro-oxidant AAA microenvironment favors macrophages with an endotoxin-tolerant-like phenotype characterized by a diminished capacity to produce pro-inflammatory mediators that enhance the immune response.

The Effect of an 8 Week Prescribed Exercise and Low-Carbohydrate Diet on Cardiorespiratory Fitness, Body Composition and Cardiometabolic Risk Factors in Obese Individuals: A Randomised Controlled Trial.

BACKGROUND: Low-carbohydrate (LC) diets are an effective method for treating obesity and reducing cardiometabolic risk. However, exposure to LC diets is associated with reductions in muscle mass and increased osteoporosis risk in obese individuals. The combination of exercise with a LC diet appears to attenuate muscle mass loss induced by LC diets alone, and to further improve cardiometabolic profile. However, evidence to date in obese individuals is limited. We assessed the effect of LC diet in combination with supervised exercise on cardiorespiratory fitness, body composition and cardiometabolic risk factors in obese individuals. Methods: Male and female participants in the experimental (EX-LC; structured supervised exercise program + low-carbohydrate meals; n = 33; 35.3 years) and control (EX-CO; structured supervised exercise program + standard dietary advice; n = 31; 34.2 years) conditions underwent measurements of cardiorespiratory fitness (VO2peak), body fat, lean muscle mass (LMM), and cardiometabolic biomarkers before and after an 8 week intervention. Results: Participants in the EX-LC condition demonstrated greater improvements in VO2peak (p = 0.002) and fat mass index (FMI, p = 0.001) compared to the EX-CO condition. Achieving a ketogenic state (ß-hydroxybutyrate, ßHB ≥0.3 mmol/L) was associated with greater reductions in total body fat (p = 0.011), visceral adipose tissue (p = 0.025), FMI (p = 0.002) and C-reactive protein (CRP, p = 0.041) but also with greater reductions in LMM (p = 0.042). Conclusion: Short-term LC diet combined with prescribed exercise enhanced cardiorespiratory fitness and the cardiometabolic profile of obese individuals but was also associated with greater muscle mass loss compared to similar exercise training and standard dietary advice. The long-term effects of the LC diet should be further explored in future studies.

Aortic and Systemic Arterial Stiffness Responses to Acute Exercise in Patients With Small Abdominal Aortic Aneurysms.

OBJECTIVE/BACKGROUND: Elevated arterial stiffness is a characteristic of abdominal aortic aneurysm (AAA), and is associated with AAA growth and cardiovascular mortality. A bout of exercise transiently reduces aortic and systemic arterial stiffness in healthy adults. Whether the same response occurs in patients with AAA is unknown. The effect of moderate- and higher intensity exercise on arterial stiffness was assessed in patients with AAA and healthy adults. METHODS: Twenty-two men with small diameter AAAs (36 ± 5 mm; mean age 74 ± 6 years) and 22 healthy adults (mean age 72 ± 5 years) were included. Aortic stiffness was measured using carotid to femoral pulse wave velocity (PWV), and systemic arterial stiffness was estimated from the wave reflection magnitude (RM) and augmentation index (Alx75). Measurements were performed at rest and during 90 min of recovery following three separate test sessions in a randomised order: (i) moderate intensity continuous exercise; (ii) higher intensity interval exercise; or (iii) seated rest. RESULTS: At rest, PWV was higher in patients with AAA than in healthy adults (p < .001), while AIx75 and RM were similar between groups. No differences were observed between AAA patients and healthy adults in post-exercise aortic and systemic arterial stiffness after either exercise protocol. When assessed as the change from baseline (delta, Δ), post-exercise ΔAIx75 was not different to the seated rest protocol. Conversely, post-exercise ΔPWV and ΔRM were both lower at all time points than seated rest (p < .001). ΔPWV was lower immediately after higher intensity than after moderate intensity exercise (p = .015). CONCLUSION: High resting aortic stiffness in patients with AAA is not exacerbated after exercise. There was a similar post-exercise attenuation in arterial stiffness between patients with AAA and healthy adults compared with seated rest. This effect was most pronounced following higher intensity interval exercise, suggesting that this form of exercise may be a safe and effective adjunctive therapy for patients with small AAAs.

Omega-3 fatty acids decrease oxidative stress and inflammation in macrophages from patients with small abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to limit oxidative stress in animal models of AAA. The aim of this study was to evaluate the effect of the n-3 PUFA docosahexaenoic acid (DHA) on antioxidant defence in macrophages from patients with AAA. Cells were obtained from men with small AAA (diameter 3.0-4.5 cm, 75 ± 6 yr, n = 19) and age- matched male controls (72 ± 5 yr, n = 41) and incubated with DHA for 1 h before exposure to 0.1 µg/mL lipopolysaccharide (LPS) for 24 h. DHA supplementation decreased the concentration of tumour necrosis factor-α (TNF-α; control, 42.1 ± 13.6 to 5.1 ± 2.1 pg/ml, p < 0.01; AAA, 25.2 ± 9.8 to 1.9 ± 0.9 pg/ml, p < 0.01) and interleukin-6 (IL-6; control, 44.9 ± 7.7 to 5.9 ± 2.0 pg/ml, p < 0.001; AAA, 24.3 ± 5.2 to 0.5 ± 0.3 pg/ml, p < 0.001) in macrophage supernatants. DHA increased glutathione peroxidase activity (control, 3.2 ± 0.3 to 4.1 ± 0.2 nmol/min/ml/µg protein, p = 0.004; AAA, 2.3 ± 0.5 to 3.4 ± 0.5 nmol/min/ml/µg protein, p = 0.008) and heme oxygenase-1 mRNA expression (control, 1.5-fold increase, p < 0.001). The improvements in macrophage oxidative stress status serve as a stimulus for further investigation of DHA in patients with AAA.

n-3 PUFAs improve erythrocyte fatty acid profile in patients with small AAA: a randomized controlled trial.

Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyte fatty acid content in 43 AAA patients (diameter 3.0-4.5 cm) and 52 healthy controls. In addition, the effect of omega-3 PUFA (n-3 PUFA) supplementation on erythrocyte fatty acid content was examined in a cohort of 30 AAA patients as part of a 12 week randomized placebo-controlled clinical trial. Blood analyses identified associations between AAA and decreased linoleic acid (LA), and AAA and increased Δ6-desaturase activity and biosynthesis of arachidonic acid (AA) from LA. Omega-3 PUFA supplementation (1.5 g DHA + 0.3 g EPA/day) decreased red blood cell distribution width (14.8 ± 0.4% to 13.8 ± 0.2%; P = 0.003) and levels of pro-inflammatory n-6 PUFAs (AA, 12.46 ± 0.23% to 10.14 ± 0.3%, P < 0.001; adrenic acid, 2.12 ± 0.13% to 1.23 ± 0.09%; P < 0.001). In addition, Δ-4 desaturase activity increased (DHA/docosapentaenoic acid ratio, 1.85 ± 0.14 to 3.93 ± 0.17; P < 0.001) and elongase 2/5 activity decreased (adrenic acid/AA ratio, 0.17 ± 0.01 to 0.12 ± 0.01; P < 0.01) following supplementation. The findings suggest that n-3 PUFAs improve fatty acid profiles and ameliorate factors associated with inflammation in AAA patients.

Reliability of arterial stiffness indices at rest and following a single bout of moderate-intensity exercise in older adults.

Short-term changes in arterial stiffness with exercise are proposed to better reflect vascular impairments than resting measures alone and are suggested as a prognostic indicator of cardiovascular risk in older adults. Arterial stiffness indices are reliable at rest, but the time-course and reliability of postexercise changes in arterial stiffness in older adults are unknown. The precision of postexercise changes in arterial stiffness should be determined prior to their use in large prospective trials. This study assessed the between-day reliability of the changes in pulse wave velocity (PWV), augmentation index (AIx75) and reflection magnitude (RM) following an exercise bout in older adults. Ten older adults (71 ± 5 years) were tested on three separate days, 7 days apart. PWV, AIx75 and RM were assessed at rest, immediately post and at 20, 40 and 60 min during recovery after moderate-intensity cycling. Intraclass correlation coefficient (ICC) and reliability coefficient (RC) were used to assess the relative and absolute reliability of arterial stiffness responses. PWV increased, and RM decreased immediately after exercise (P<0·05), and returned to baseline during recovery. AIx decreased during recovery (P<0·001). Resting ICC values were 0·91 (PWV), 0·72 (AIx75) and 0·40 (RM). Reliability of the immediate changes following exercise was high for PWV (ICC:0·87, RC:1·9 m s-1 ) and moderate for AIx75 (ICC:0·64, RC:7%) and RM (ICC:0·59, RC:9%). Reliability of the postexercise responses was similar to that at rest for all measures of arterial stiffness. These findings indicate that postexercise changes in arterial stiffness indices are reliable in healthy older adults and supports further investigation of the prognostic value of these responses.

Effects of exercise intensity and cardiorespiratory fitness on the acute response of arterial stiffness to exercise in older adults.

PURPOSE: Increased arterial stiffness is observed with ageing and in individuals with low cardiorespiratory fitness ([Formula: see text]O2peak), and associated with cardiovascular risk. Following an exercise bout, transient arterial stiffness reductions offer short-term benefit, but may depend on exercise intensity. This study assessed the effects of exercise intensity on post-exercise arterial stiffness in older adults with varying fitness levels. METHODS: Fifty-one older adults (72 ± 5 years) were stratified into fitness tertiles ([Formula: see text]O2peak: low-, 22.3 ± 3.1; mid-, 27.5 ± 2.4 and high-fit 36.3 ± 6.5 mL kg-1 min-1). In a randomised order, participants underwent control (no-exercise), moderate-intensity continuous exercise (40% of peak power output; PPO), and higher-intensity interval exercise (70% of PPO) protocols. Pulse wave velocity (PWV), augmentation index (AIx75) and reflection magnitude (RM) were assessed at rest and during 90 min of recovery following each protocol. RESULTS: After control, delta PWV increased over time (P < 0.001) and delta RM was unchanged. After higher-intensity interval exercise, delta PWV (P < 0.001) and delta RM (P < 0.001) were lower to control in all fitness groups. After moderate-intensity continuous exercise, delta PWV was not different from control in low-fit adults (P = 0.057), but was lower in the mid- and higher-fit older adults. Post-exercise AIx75 was higher to control in all fitness groups (P = 0.001). CONCLUSIONS: In older adults, PWV increases during seated rest and this response is attenuated after higher-intensity interval exercise, regardless of fitness level. This attenuation was also observed after moderate-intensity continuous exercise in adults with higher, but not lower fitness levels. Submaximal exercise reveals differences in the arterial stiffness responses between older adults with higher and lower cardiorespiratory fitness.

Cytokine Responses to Acute Exercise in Healthy Older Adults: The Effect of Cardiorespiratory Fitness.

Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6]) and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]). However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α) and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg-1.min-1) and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg-1.min-1) completed three 24 min experimental protocols in a randomized order: (1) moderate-intensity continuous exercise (40% of peak power output [PPO]); (2) higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO); or (3) non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02), with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01). However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control) protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6 were elevated in older individuals with higher levels of cardiorespiratory fitness. However, changes in plasma cytokine concentrations after exercise were not different to changes after non-exercise control in both the lower- and higher-fit groups.

Effects of acute exercise on endothelial function in patients with abdominal aortic aneurysm.

Endothelial dysfunction is observed in patients with abdominal aortic aneurysm (AAA), who have increased risk of cardiovascular events and mortality. This study aimed to assess the acute effects of moderate- and higher-intensity exercise on endothelial function, as assessed by flow-mediated dilation (FMD), in AAA patients (74 ± 6 yr old, n = 22) and healthy adults (72 ± 5 yr old, n = 22). Participants undertook three randomized visits, including moderate-intensity continuous exercise [40% peak power output (PPO)], higher-intensity interval exercise (70% PPO), and a no-exercise control. Brachial artery FMD was assessed at baseline and at 10 and 60 min after each condition. Baseline FMD was lower [by 1.10% (95% confidence interval: 0.72-.81), P = 0.044] in AAA patients than in healthy adults. There were no group differences in FMD responses after each condition ( P = 0.397). FMD did not change after no-exercise control but increased by 1.21% (95% confidence interval: 0.69-1.73, P < 0.001) 10 min after moderate-intensity continuous exercise in both groups and returned to baseline after 60 min. Conversely, FMD decreased by 0.93% (95% confidence interval: 0.41-1.44, P < 0.001) 10 min after higher-intensity interval exercise in both groups and remained decreased after 60 min. We found that the acute response of endothelial function to exercise is intensity-dependent and similar between AAA patients and healthy adults. Our findings provide evidence that regular exercise may improve vascular function in AAA patients, as it does in healthy adults. Improved FMD after moderate-intensity exercise may provide short-term benefit. Whether the decrease in FMD after higher-intensity exercise represents an additional risk and/or a greater stimulus for vascular adaptation remains to be elucidated. NEW & NOTEWORTHY Abdominal aortic aneurysm patients have vascular dysfunction. We observed a short-term increase in vascular function after moderate-intensity exercise. Conversely, higher-intensity exercise induced a prolonged reduction in vascular function, which may be associated with both short-term increases in cardiovascular risk and signaling for longer-term vascular adaptation in abdominal aortic aneurysm patients.

Acute Inflammatory Responses to Exercise in Patients with Abdominal Aortic Aneurysm.

PURPOSE: Inflammation and extracellular matrix degeneration contribute to abdominal aortic aneurysm (AAA) development. We aimed to assess the effect of exercise intensity on circulating biomarkers of inflammation and extracellular matrix degeneration in patients with AAA and healthy older adults. METHODS: Twenty patients with AAA (74 ± 6 yr) and 20 healthy males (72 ± 5 yr) completed moderate-intensity cycling at 40% peak power output, higher-intensity intervals at 70% peak power output, and control (rest) on separate days. Circulating matrix metalloproteinase-9 (MMP-9), transforming growth factor beta 1, interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-α) were analyzed at rest and 0 to 90 min postexercise. RESULTS: Biomarkers at baseline were similar between groups. IL-6 responses to exercise were similar between groups, with a greater increase in ΔIL-6 after moderate-intensity compared with higher-intensity exercise (P < 0.001). Delta MMP-9 showed a 118-ng·mL (95% confidence interval = 23 to 214, P = 0.02) greater increase immediately after higher-intensity exercise compared with changes in control in both groups. Delta MMP-9 then decreased by 114 ng·mL (18 to 211, P = 0.02) 90 min after higher-intensity exercise compared with the changes in control. Delta TNF-α was not different between protocols in healthy adults. In patients with AAA, delta TNF-α showed a greater decrease after higher-intensity compared with moderate-intensity exercise (-6.1 pg·mL, -8.5 to -3.6, P < 0.001) and control (-4.9 pg·mL, -7.4 to -2.4, P < 0.001). IL-10 and transforming growth factor beta 1 did not change in either group. CONCLUSIONS: These findings suggest that a bout of higher-intensity exercise elicits a greater anti-inflammatory response compared with moderate-intensity exercise, which may be further augmented in patients with AAA. Exercise-induced reductions in biomarkers associated with AAA progression may represent a protective effect of exercise in patients with AAA.

Cardiorespiratory fitness modulates the acute flow-mediated dilation response following high-intensity but not moderate-intensity exercise in elderly men.

Impaired endothelial function is observed with aging and in those with low cardiorespiratory fitness (V̇o2peak). Improvements in endothelial function with exercise training are somewhat dependent on the intensity of exercise. While the acute stimulus for this improvement is not completely understood, it may, in part, be due to the flow-mediated dilation (FMD) response to acute exercise. We examined the hypothesis that exercise intensity alters the brachial (systemic) FMD response in elderly men and is modulated by V̇o2peak Forty-seven elderly men were stratified into lower (V̇o2peak = 24.3 ± 2.9 ml·kg-1·min-1; n = 27) and higher fit groups (V̇o2peak = 35.4 ± 5.5 ml·kg-1·min-1; n = 20) after a test of cycling peak power output (PPO). In randomized order, participants undertook moderate-intensity continuous exercise (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO) or no-exercise control. Brachial FMD was assessed at rest and 10 and 60 min after exercise. FMD increased after MICE in both groups {increase of 0.86% [95% confidence interval (CI), 0.17-1.56], P = 0.01} and normalized after 60 min. In the lower fit group, FMD was reduced after HIIE [reduction of 0.85% (95% CI, 0.12-1.58), P = 0.02] and remained decreased at 60 min. In the higher fit group, FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52% (95% CI, 0.41-2.62), P < 0.01, which was correlated with V̇o2peak, r = 0.41; P < 0.01]. In the no-exercise control, FMD was reduced in both groups after 60 min (P = 0.05). Exercise intensity alters the acute FMD response in elderly men and V̇o2peak modulates the FMD response following HIIE but not MICE. The sustained decrease in FMD in the lower fit group following HIIE may represent a signal for vascular adaptation or endothelial fatigue.NEW & NOTEWORTHY This study is the first to show that moderate-intensity continuous cycling exercise increased flow-mediated dilation (FMD) transiently before normalization of FMD after 1 h, irrespective of cardiorespiratory fitness level in elderly men. Interestingly, we show increased FMD after high-intensity cycling exercise in higher fit men, with a sustained reduction in FMD in lower fit men. The prolonged reduction in FMD after high-intensity cycling exercise may be associated with future vascular adaptation but may also reflect a period of increased cardiovascular risk in lower fit elderly men.