Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Hospitalizations Among Adults With CKD in Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia.

Rationale & Objective: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). Study Design: Retrospective observational cohort study. Setting & Participants: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018. Predictors: Demographic and clinical characteristics of patients with CKD. Outcomes: Hospital admissions. Analytical Approach: We evaluated the association of demographic and clinical features with hospitalizations, length of hospital stay, and cost. Results: Approximately 81.5% of the patients were admitted at least once, with 42,283 admissions, costing Australian dollars (AUD) 231 million. The average number of admissions per person-year was 1.7, and the cost was AUD 9,060, 10 times and 2 times their Australian averages, respectively. Single (1-day) admissions constituted 59.2% of all the hospital episodes, led by neoplasms (largely chemotherapy), anemia, CKD-related conditions and eye conditions (largely cataract extractions), but only 14.8% of the total costs. Approximately 41% of admissions were >1-day admissions, constituting 85.2% of the total costs, with cardiovascular conditions, respiratory conditions, CKD-related conditions, and injuries, fractures, or poisoning being the dominant causes. Readmission within 30 days of discharge constituted >42% of the admissions and 46.8% costs. Admissions not directly related to CKD constituted 90% of the admissions and costs. More than 40% of the admissions and costs were through the emergency department. Approximately 19% of the hospitalized patients and 27% of the admissions did not have kidney disease mentioned as either principal or associate causes. Limitations: Variable follow-up times because of different dates of consent. Conclusions: The hospital burden of patients with CKD is mainly driven by complex multiday admissions and readmissions involving comorbid conditions, which may not be directly related to their CKD. Strategies to prevent these complex admissions and readmissions should minimize hospital costs and outcomes. Plain-Language Summary: We analyzed primary causes, types, and costs of hospitalizations among 7,201 patients with chronic kidney disease (CKD) from renal speciality clinics across Queensland, Australia, over an average follow-up of 3.54 years. The average annual cost per person was $9,060, and was the highest in those with more advanced CKD, higher age, and with diabetes. More than 85% of costs were driven by more complex hospitalizations with longer length of stay. Cardiovascular disease was the single largest contributor for hospitalizations, length of hospital stay, and total costs. Readmission within 30 days of discharge, particularly for the same disorder, and multiday admissions should be the main targets for mitigation of hospital costs in this population.

Efficacy of two doses of external counterpulsation (ECP) on glycemic control in people with type 2 diabetes mellitus: A randomized SHAM-controlled trial.

AIMS: To determine the efficacy of two doses of external counterpulsation (ECP) on glycemic control in people with type 2 diabetes mellitus (T2D), and any persistent benefits 7 weeks following treatment. METHODS: 50 participants with T2D were randomly assigned to either 1) 20x45-minute ECP sessions over 7 weeks (ECP45), 2) 20x30-minute ECP sessions over 7 weeks (ECP30) or 3) SHAM control. Outcomes were assessed at baseline, after 7 weeks of the intervention and 7 weeks after the interventions finished. Efficacy was determined from changes in HbA1c. RESULTS: After 7 weeks, there were significant between-group differences, with ECP45 lowering HbA1c compared to SHAM (mean [95% CI] -0.7 [-0.1 to -1.3] %; -7 [-1 to -15] mmol/mol). Within group changes were; ECP45 (mean ± SD -0.8 ± 0.8%; -8 ± 8 mmol/mol), ECP30 (-0.2 ± 0.5%; -2 ± 6 mmol/mol) and SHAM (-0.1 ± 0.9%; -1 ± 10 mmol/mol). HbA1c in the ECP45 group remained lower 7 weeks after completing the intervention; ECP45 (7.0 ± 1.1%; 53 ± 26 mmol/mol), ECP30 (7.7 ± 1.4%; 60 ± 16 mmol/mol) and SHAM (7.7 ± 1.0%; 60 ± 10 mmol/mol). CONCLUSIONS: In people with T2D, ECP45 for 7 weeks improved glycemic control when compared to ECP30 and a SHAM control group.

Chronic kidney disease in public renal practices in Queensland, Australia, 2011-2018.

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland. METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years. RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons mostly had diabetic nephropathy, renovascular disease and multiple diagnoses. Proportions of specific renal diagnoses varied >2-fold across sites. Over the first year, eGFR fell in 24% but was stable or improved in 76%. Over follow up, 10% started KRT, at a median age of 62 yr, most with CKD stages 4 and 5 at consent, while 18.8% died without KRT, at a median age of 80 yr. Indigenous people were younger at consent and more often had diabetes and diabetic kidney disease and had higher incidence rates of KRT. CONCLUSION: The spectrum of characteristics in CKD patients in renal practices is much broader than represented by the minority who ultimately start KRT. Variation in CKD by causes, age, site and Indigenous status, the prevalence of obesity, relative stability of kidney function in many persons over the short term, and differences between those who KRT and die without KRT are all important to explore.

Effects of fitness and fatness on age-related arterial stiffening in people with type 2 diabetes.

People with type 2 diabetes (T2D) are at a greater risk of cardiovascular disease than the general population. Both non-modifiable (age) and modifiable (low aerobic fitness, high body fatness) factors are separately predictive of cardiovascular risk, although they often occur concomitantly. This study aimed to examine the (1) association between age and arterial stiffness, a subclinical marker of cardiovascular risk; and (2) effects of body fatness and aerobic fitness on age-related increases in arterial stiffness in people with T2D. Data from 64 individuals with T2D (age 59.8 ± 8.7 years, 40% female, HbA1c 8.4 ± 1.6%) were included in this cross-sectional analysis. Carotid-femoral pulse wave velocity (cfPWV) was used to quantify arterial stiffness. Aerobic fitness (relative V̇O2peak ) was determined via indirect calorimetry during maximal exercise testing. Central body fatness was determined using waist circumference. Data were analysed using hierarchical multiple regressions. After adjustment for sex and duration of T2D, each one standard deviation (SD) increase in age (8.68 years) was associated with a 0.63 m·s-1 increase in cfPWV (ß = 0.416, p = 0.001). Following adjustment for aerobic fitness and body fatness, the standardized ß was unchanged (0.417). A one SD increase in waist circumference (13.9 cm) and relative V̇O2peak (5.3 ml·kg-1 ·min-1 ) were associated with a similar magnitude of difference in cfPWV (0.47 m·s-1 and -0.44 m·s-1 , respectively). Therefore, age is a significant correlate of increased arterial stiffness in T2D, with higher aerobic fitness attenuating, and higher body fatness exacerbating, this increase. Interventions aimed at improving cardiovascular outcomes in people with T2D should target both increased aerobic fitness and reduced body fatness.

Personal Activity Intelligence e-Health Program in People with Type 2 Diabetes: A Pilot Randomized Controlled Trial.

INTRODUCTION: Innovative strategies are needed to enable people with type 2 diabetes (T2D) to self-manage physical activity (PA). Personal Activity Intelligence (PAI) is a new metric that uses the heart rate response to PA to inform the user as to whether they are doing enough PA to reduce the risk of premature mortality. The PAI score reflects PA over the previous 7 d with the goal to maintain a score ≥100. The aim of this study was to investigate the feasibility, acceptability, and efficacy of the PAI e-Health Program in people with T2D. METHODS: Thirty participants with T2D who were not meeting PA guidelines were randomly assigned to 12 wk of either 1) PAI e-Health Program or 2) PA attention control. The PAI e-Health Program consisted of receiving a wrist-worn heart rate monitor and an app with the PAI metric, and attending 4 × 2 h·wk-1 sessions of exercise and counseling. Feasibility and acceptability of the program were evaluated by achievement of a PAI score ≥100 and participant feedback. Efficacy was determined from changes in glycemic control, cardiorespiratory fitness, exercise capacity (time-on-test), body composition, sleep time, and health-related quality of life. RESULTS: Program participants in the PAI e-Health Program had a mean ± SD PAI score of 119.7 ± 60.6 and achieved ≥100 PAI on 56.4% of the days. The majority of participants (80%) intended to continue to use PAI monitoring. Compared with control, the PAI group significantly improved their exercise capacity (mean difference, 95% confidence interval) (63 s, 17.9-108.0 s), sleep time (67.2 min, 7.2-127.1 min), total percent body fat (-1.3%, -2.6% to -0.1%), and gynoid fat percent (-1.5%, -2.6 to -0.5). CONCLUSIONS: The PAI e-Health Program is feasible, acceptable, and efficacious in people with T2D.

Exercise Training Intensity and the Fitness-Fatness Index in Adults with Metabolic Syndrome: A Randomized Trial.

BACKGROUND: Cardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone. OBJECTIVE: This study sought to investigate the effects of different exercise intensities on FFI in adults with MetS. METHODS: This was a sub-study of the 'Exercise in the prevention of Metabolic Syndrome' (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60-70% HRpeak for 30 min/session (n = 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85-95% HRpeak, interspersed with 3-min active recovery at 50-70% HRpeak (n = 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85-95% HRpeak (n = 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O2peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase. RESULTS: Seventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (p = 0.30), there was a small group x time interaction effect on FFI [F(2, 73) = 1.226; η2 = 0.01], with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (p = 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14). CONCLUSION: Although there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted. Trial registration number and date of registration: ClinicalTrials.gov NCT01676870; 31/08/2012.

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Effect of Different Volumes of Interval Training and Continuous Exercise on Interleukin-22 in Adults with Metabolic Syndrome: A Randomized Trial.

INTRODUCTION: IL-22 may have a role in the alleviation of the metabolic syndrome (MetS) via protection of pancreatic beta and endothelial cells from oxidative and lipid-induced damage. We aimed to investigate the effects of moderate-intensity continuous training (MICT) and different volumes of high-intensity interval training (HIIT) on changes in circulating IL-22. METHODS: This was a sub-study of the "Exercise in the prevention of Metabolic Syndrome" (EX-MET) a multi-center, randomized trial. This study used data collected at the Brisbane site. Thirty-nine individuals with MetS were randomized to one of three 16-wk interventions: 1) MICT (n=10, 30min at 60-70% HR peak, 5x/wk); 2) 4HIIT (n=13, 4x4min at 85-95% HR peak, interspersed with 3min of active recovery at 50-70% HR peak, 3x/wk); or 3) 1HIIT (n=16, 1x4min at 85-95% HR peak, 3x/wk). Serum IL-22 concentration was measured following a 12-hr fast via an enzyme linked immunosorbent assay, before and after the intervention. MetS severity, insulin resistance (IR), visceral adipose tissue (VAT), and cardiorespiratory fitness (CRF) were also measured via MetS z-score, HOMA-IR, dual-energy X-ray absorptiometry, and indirect calorimetry (maximal exercise test), respectively. RESULTS: The median (IQR) IL-22% changes from pre- to post-intervention in the MICT, 4HIIT, and 1HIIT groups were -17% (-43.0% to 31.3%), +16.5% (-18.9% to 154.9%), and +15.9% (-28.7% to 46.1%), respectively. Although there were no significant between-group differences in IL-22 concentration change, there was a medium-to-large group × time interaction effect [F(2,35)=2.08, p=0.14, η2=0.14]. CONCLUSION: Although there was no statistically significant between-group difference in IL-22 change, the study suggests that different exercise intensities may have opposing effects on IL-22 concentration in individuals with MetS.

Optimizing the Interaction of Exercise Volume and Metformin to Induce a Clinically Significant Reduction in Metabolic Syndrome Severity: A Randomised Trial.

Insulin resistance is a central mediating factor of the metabolic syndrome (MetS), with exercise training and metformin proven antidotes to insulin resistance. However, when the two therapies are combined there is conflicting data regarding whether metformin blunts or improves exercise training-induced adaptations. The volume of exercise (duration, intensity, and frequency) on the interaction of exercise training and metformin has yet to be investigated. The aim of this study is therefore to explore the impact of a combination of different exercise volumes and metformin on MetS severity. This is a secondary analysis of data from one of the sites of the 'Exercise in Prevention of Metabolic Syndrome' (EX-MET) study. Ninety-nine adults with MetS were randomized into a 16-week exercise program completing either: (i) moderate-intensity continuous training (MICT) at 60-70% of peak heart rate (HRpeak) for 30 min/session (n = 34, 150 min/week); (ii) high-volume high-intensity interval training (HIIT) consisting of 4 × 4 min bouts at 85-95% HRpeak, interspersed with 3 min of active recovery at 50-70% HRpeak (n = 34, 38 min/session, 114 min/week); or (iii) low volume HIIT, 1 × 4 min bout of HIIT at 85-95% HRpeak (n = 31, 17 min/session, 51 min/week). Metformin intake was monitored and recorded throughout the trial. MetS severity was calculated as z-scores derived from MetS risk factors assessed at pre- and post-intervention. Sixty-five participants had complete pre- and post-intervention data for MetS z-score, of which 18 participants (28%) were taking metformin. Over the 16-week intervention, a similar proportion of participants clinically improved MetS severity (Δ ≥ -0.87) with metformin (8/18, 44%) or without metformin (23/47, 49%) (p = 0.75). While there were no between-group differences (p = 0.24), in those who did not take metformin low-volume HIIT had more likely responders (10/15, 67%) compared to MICT (6/16, 38%) and high-volume HIIT (7/16, 44%). In those taking metformin, there was a lower proportion of participants who clinically improved MetS severity following high-volume HIIT (1/6, 17%) compared to MICT (2/4, 50%) and low-volume HIIT (5/8, 63%), but with no between-group difference (p = 0.23). Moreover, in those who performed high-volume HIIT, there was a statistically significantly higher proportion (p = 0.03) of likely non-responders with improved MetS severity in participants taking metformin (4/6, 67%) compared to those not taking metformin (3/16, 19%). In individuals with MetS, the effect of high volume HIIT on MetS severity may be blunted in those taking metformin. These findings need to be confirmed in a larger study.

Comparing the Efficacy of Supervised and Unsupervised Exercise Training on Glycaemic Control in Type 2 Diabetes: A Systematic Review.

BACKGROUND: Exercise training is vital for glycaemic control in patients with type 2 diabetes mellitus (T2D). While the positive effects of supervised exercise training are well established, unsupervised training may offer an alternative and more sustainable means of realising the benefits of exercise away from a resource-heavy supervised setting. OBJECTIVE: To evaluate the available literature and compare the efficacy of supervised and unsupervised exercise training programs on glycemic control in patients with T2D. METHODS: CINAHL, MEDLINE, PubMed, and EMBASE, searched from inception to 20 July 2018. Only studies that included both supervised and unsupervised training were included. RESULTS: Four studies, involving 115 participants, were included. One compared supervised with unsupervised exercise training and three investigated the efficacy of unsupervised training following supervised training. While supervised training is effective for improving glycaemic control in patients with T2D, unsupervised training may not maintain these changes. Included studies lacked detail relating to the supervised and unsupervised training programs. CONCLUSIONS: Given that exercise is a critical component for maintenance of glycaemic control in patients with T2D, and because unsupervised training has been shown to be effective in improving clinical outcomes in other disease populations, further research is warranted to compare supervised and unsupervised exercise training in patients with T2D. It is important that future studies report standardised and detailed descriptions of key elements that form the basis of supervised and unsupervised exercise training groups.

Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN).

BACKGROUND: Mycophenolate mofetil or enteric-coated mycophenolate sodium (EC-MPS) and steroids are used for induction and maintenance therapy in severe lupus nephritis. Blood concentrations of mycophenolic acid (MPA), the active metabolite of these drugs, vary among patients with lupus nephritis. The objective of this study was to examine whether concentration-controlled (CC) dosing (through therapeutic drug monitoring) of EC-MPS results in a higher proportion of participants achieving target exposure of MPA compared with fixed-dosing (FD). An additional aim of the study was to evaluate the influence of CC dosing on clinical outcomes. METHODS: Nineteen participants were randomly assigned either to the FD or CC group. All the participants were eligible to have free and total measurements of MPA over a period of 8-12 hours on 3 different occasions. Area under the concentration-time curve between 0 and 12 hours (AUC0-12) was calculated using noncompartmental methods. Dose of EC-MPS was titrated according to AUC0-12 in the CC group. RESULTS: Thirty-two AUC0-12 measurements were obtained from 9 FD and 9 CC participants. Large inter-patient variability was observed in both groups but was more pronounced in the FD group. There were no significant differences between FD and CC participants in any pharmacokinetic parameters across the study visits, except for total C0 (FD 2.0 ± 0.3 mg/L versus CC 1.1 ± 0.3; P = 0.01) and dose-normalized C0 (FD 2.9 ± 0.2 mg/L/g versus CC 2.1 ± 0.7 mg/L/g; P = 0.04) at the second visit and total AUC0-12 (FD 66.6 ± 6.0 mg·h/L versus CC 35.2 ± 11.4 mg·h/L; P = 0.03) at the third visit. At the first study visit, 33.3% of the FD and 11.1% of the CC participants achieved the target area under the concentration-time curve (P = 0.58). From the second visit, none of the FD participants, compared with all the CC participants, achieved target AUC0-12 (P = 0.01). More CC participants achieved remission compared with FD participants (absolute difference of -22.2, 95% confidence interval (Equation is included in full-text article.)0.19 to 0.55; P = 0.62). The mean free MPA AUC0-12 was significantly lower in those who had complete remission. CONCLUSIONS: CC participants reached target AUC0-12 quicker. Larger studies are required to test clinical efficacy.

High-intensity interval training in chronic kidney disease: A randomized pilot study.

INTRODUCTION: High-intensity interval training (HIIT) increases mitochondrial biogenesis and cardiorespiratory fitness in chronic disease populations, however has not been studied in people with chronic kidney disease (CKD). The aim of this study was to compare the feasibility, safety, and efficacy of HIIT with moderate-intensity continuous training (MICT) in people with CKD. METHODS: Fourteen individuals with stage 3-4 CKD were randomized to 3 supervised sessions/wk for 12 weeks, of HIIT (n = 9, 4 × 4 minute intervals, 80%-95% peak heart rate [PHR]) or MICT (n = 5, 40 minutes, 65% PHR). Feasibility was assessed via session attendance and adherence to the exercise intensity. Safety was examined by adverse event reporting. Efficacy was determined from changes in cardiorespiratory fitness (VO2 peak), exercise capacity (METs), and markers of mitochondrial biogenesis (PGC1α protein levels), muscle protein catabolism (MuRF1), and muscle protein synthesis (p-P70S6k Thr389 ). RESULTS: Participants completed a similar number of sessions in each group (HIIT = 33.0[7.0] vs MICT = 33.5[3.3] sessions), and participants adhered to the target heart rates. There were no adverse events attributable to exercise training. There was a significant time effect for exercise capacity (HIIT = +0.8 ± 1.2; MICT = +1.3 ± 1.6 METs; P = 0.01) and muscle protein synthesis (HIIT = +0.6 ± 1.1; MICT = +1.4 ± 1.7 au; P = 0.04). However, there were no significant (P > 0.05) group × time effects for any outcomes. CONCLUSION: This pilot study demonstrated that HIIT is a feasible and safe option for people with CKD, and there were similar benefits of HIIT and MICT on exercise capacity and skeletal muscle protein synthesis. These data support a larger trial to further evaluate the effectiveness of HIIT.

Fibre Intake Is Independently Associated with Increased Circulating Interleukin-22 in Individuals with Metabolic Syndrome.

The positive effects of dietary fibre on gut barrier function and inflammation have not been completely elucidated. Mice studies show gut barrier disruption and diet-induced insulin resistance can be alleviated by cytokine interleukin-22 (IL-22). However, little is known about IL-22 in humans and its association with gut-beneficial nutrients like fibre. We investigated whether fibre intake was associated with circulating levels of IL-22 in 48 participants with metabolic syndrome (MetS). Bivariate analysis was used to explore associations between circulating IL-22, fibre intake, MetS factors, body composition, and cardiorespiratory fitness (peak oxygen uptake, V ˙ O2peak). Hierarchical multiple regression (HMR) was used to test the independent association of fibre intake with circulating IL-22, adjusting for variables correlated with IL-22. Circulating IL-22 was positively associated with fibre intake (rs = 0.393, p < 0.006). The HMR-adjusted model explained 40% of circulating IL-22 variability, and fibre intake significantly improved the prediction model by 8.4% (p < 0.022). Participants with fibre intake above median intake of 21.5 g/day had a significantly higher circulating IL-22 than the lower intake group (308.3 ± 454.4 vs. 69.0 ± 106.4 pg/mL, p < 0.019). Fibre intake is independently associated with increased circulating IL-22 in individuals with MetS. Findings warrant further investigations to evaluate whether changes in dietary fibre intake alter circulating IL-22, and its effects on health outcomes.

The association between metabolic syndrome severity and oxidative stress induced by maximal exercise testing - a cross-sectional study.

Purpose: Oxidative stress (OS) has been implicated in the pathogenesis of metabolic syndrome (MetS). The acute change in OS biomarkers due to exercise, known as exercise-induced OS (EIOS), is postulated to be a more appropriate marker of OS compared to spot OS measures. These studies objectives were to investigate EIOS in participants with MetS and compare the associations between EIOS, spot OS measures and MetS severity. Methods: Sixty-three participants with MetS had MetS severity assessed using the MetS Z-score. Participants undertook a cardiorespiratory fitness test ( V O2peak) to volitional exhaustion (∼8-12 minutes). Plasma OS (total F2-isoprostanes (IsoP), protein carbonyls (PCs)) and antioxidant (glutathione peroxidase (GPx), total antioxidant status (TAS)) biomarkers were measured from samples obtained before and five minutes post- V O2peak test. Wilcoxon's signed-rank tests were used to determine changes in OS markers. Results: There were no significant (p > 0.05) changes in OS or antioxidant biomarkers from pre- to post-exercise (median (interquartile range): IsoP -15.5 (-71.8 to 47.8) pg/mL; PC -0.01 (-0.16 to 0.13) nmol/mg protein; GPx 0.76 (-4.94 to 9.82) U/L, TAS 0.03 (0.00-0.05) mmol/L). Conclusions: A V O2peak test to exhaustion failed to induce OS in participants with MetS. There were no associations between MetS severity and spot OS or EIOS biomarkers.

A Multi-Center Comparison of O2peak Trainability Between Interval Training and Moderate Intensity Continuous Training.

There is heterogeneity in the observed O2peak response to similar exercise training, and different exercise approaches produce variable degrees of exercise response (trainability). The aim of this study was to combine data from different laboratories to compare O2peak trainability between various volumes of interval training and Moderate Intensity Continuous Training (MICT). For interval training, volumes were classified by the duration of total interval time. High-volume High Intensity Interval Training (HIIT) included studies that had participants complete more than 15 min of high intensity efforts per session. Low-volume HIIT/Sprint Interval Training (SIT) included studies using less than 15 min of high intensity efforts per session. In total, 677 participants across 18 aerobic exercise training interventions from eight different universities in five countries were included in the analysis. Participants had completed 3 weeks or more of either high-volume HIIT (n = 299), low-volume HIIT/SIT (n = 116), or MICT (n = 262) and were predominately men (n = 495) with a mix of healthy, elderly and clinical populations. Each training intervention improved mean O2peak at the group level (P < 0.001). After adjusting for covariates, high-volume HIIT had a significantly greater (P < 0.05) absolute O2peak increase (0.29 L/min) compared to MICT (0.20 L/min) and low-volume HIIT/SIT (0.18 L/min). Adjusted relative O2peak increase was also significantly greater (P < 0.01) in high-volume HIIT (3.3 ml/kg/min) than MICT (2.4 ml/kg/min) and insignificantly greater (P = 0.09) than low-volume HIIT/SIT (2.5 mL/kg/min). Based on a high threshold for a likely response (technical error of measurement plus the minimal clinically important difference), high-volume HIIT had significantly more (P < 0.01) likely responders (31%) compared to low-volume HIIT/SIT (16%) and MICT (21%). Covariates such as age, sex, the individual study, population group, sessions per week, study duration and the average between pre and post O2peak explained only 17.3% of the variance in O2peak trainability. In conclusion, high-volume HIIT had more likely responders to improvements in O2peak compared to low-volume HIIT/SIT and MICT.

CKD Screening and Surveillance in Australia: Past, Present, and Future.

Chronic kidney disease (CKD) was largely a hidden health problem until the publication of an internationally agreed approach to its identification, monitoring, and treatment. The 2002 National Kidney Foundation CKD classification and the subsequent 2006 Kidney Disease Improving Global Outcomes (KDIGO) recommendations are powerful tools for translating thinking about CKD into clinical practice. These guidelines were strongly endorsed by the international community, including Australia, and were incorporated into CKD practice guidelines. In the past, CKD research studies in Australia focused on screening the general population, and more specifically, individuals at risk for CKD. Information from these studies led to the recognition that the CKD burden in Australia is a public health problem and contributed to the development of national health policies and priorities. At present, apart from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) that reports on CKD patients undergoing renal replacement therapy (RRT), long-term surveillance to describe the natural history of the CKD population not on RRT has only recently started. Entities such as CKD. Queensland and the Western Australian Nephrology Database are able to fill the gap and provide opportunities for collaborative research of CKD in Australia. Establishment of a National Health and Medical Research Centre-funded CKD Centre of Excellence in 2015 and the Better Evidence and Translation-Chronic Kidney Disease in 2016 are likely to change the future of CKD surveillance and research in Australia.

Low-Volume High-Intensity Interval Training Is Sufficient to Ameliorate the Severity of Metabolic Syndrome.

BACKGROUND: High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) at improving cardiometabolic risk. However, the optimal volume of HIIT to reduce the severity of the metabolic syndrome (MetS) has yet to be investigated. The aim of this study was to examine the impact of different volumes of HIIT and MICT on MetS severity (MetS z-score). METHODS: This was a substudy of the "Exercise in prevention of Metabolic Syndrome" (EX-MET) multicenter trial, reporting data collected at the Brisbane site. Ninety-nine adults diagnosed with MetS were randomized to one of the following 16-week interventions: (1) MICT [n = 34, 30 min at 60%-70% heart rate (HR) peak/session, 150 min/week]; (2) 4HIIT (n = 34, 4 × 4 min bouts at 85%-95% HR peak, interspersed with 3 min active recovery at 50%-70% HR peak, 114 min/week); or (3) 1HIIT (n = 31, 1 × 4 min bout at 85%-95% HR peak, 51 min/week). Z-scores were derived from levels of MetS risk factors before and after the intervention. RESULTS: Eighty-one participants completed post-testing (MICT, n = 26; 4HIIT, n = 28, 1HIIT, n = 27). After excluding 16 participants who had a change in medication dosage or type during the intervention, a total of 65 participants were included in the analysis [MICT, n = 22, age 55 ± 10 years, body mass index (BMI) 32 ± 6 kg/m; 4HIIT, n = 22, 56 ± 10 years, 35 ± 9 kg/m2; 1HIIT, n = 21, 57 ± 8 years, 32 ± 5 kg/m). MetS severity reduced following all interventions (pre- to post-MetS z-score: MICT, 1.80 ± 1.93 to 0.90 ± 1.93; 4HIIT, 2.75 ± 2.56 to 2.17 ± 2.71; 1HIIT, 2.48 ± 3.38 to 0.84 ± 2.98), with no significant differences between groups. There were no reported adverse events that were directly related to the exercise interventions. CONCLUSIONS: Low-volume HIIT (51 min/week) was as effective as high-volume HIIT (114 min/week) and MICT (150 min/week) in ameliorating MetS severity.

High-intensity interval training and cardiac autonomic control in individuals with metabolic syndrome: A randomised trial.

BACKGROUND: Insulin resistance has been postulated to play a central role in the co-appearance of various cardiovascular disease risk factors constituting the metabolic syndrome (MetS). There is evidence that altered cardiac autonomic function (CAF) may precede the onset of insulin resistance. Exercise training has been shown to improve CAF in different populations, yet little is known regarding the exercise dose response for CAF. The aim of this study was to investigate the impact of different volumes of high-intensity interval training (HIIT) and traditional moderate-intensity continuous training (MICT) on CAF in participants with MetS. METHODS: Individuals with MetS (n=56) were randomised into the following 16-week training interventions: i) MICT (n=16, 30min at 60-70%HRpeak, 5×/week); ii) 4HIIT (n=19, 4×4min bouts at 85-95%HRpeak, interspersed with 3min of active recovery at 50-70%HRpeak, 3×/week); or iii) 1HIIT (n=21, 1×4min bout at 85-95%HRpeak, 3×/week). R-R interval recorded for 5min in a supine position at pre- and post-intervention was used to derive linear (SDNN, RMSSD, pNN50, LF, HF, LF/HF) and non-linear (SD1, SD2, Alpha1, Alpha2, SampEn) heart rate variability (HRV) indices as measures of CAF. Group×time interaction effects were examined (ANCOVA) and Eta squared (η2) interaction effect sizes calculated. RESULTS: While there were no significant between-group differences in CAF indices, there were small-to-medium group×time interaction effects on SDNN [F(2,52)=0.70, p=0.50, η2=0.02], RMSSD [F(2,52)=1.35, p=0.27, η2=0.03], HF power [F(2,52)=1.27, p=0.29, η2=0.03], SD1 [F(2,52)=0.47, p=0.63, η2=0.01], and SD2 [F(2,52)=0.41, p=0.67, η2=0.01]. The following represent the relative percentage increases across these variables for 4HIIT, MICT, and 1HIIT respectively (SDNN, +30%, +17%, 9%; RMSSD, +30%, +22%, -2%; HF power, +69%, +18%, +7%; SD1, +30%, +22%,-2%; SD2, +22%, +14%, 4%). CONCLUSIONS: There were no significant between-group differences for the effects of exercise dose on CAF indices, however; high-volume HIIT demonstrated the greatest magnitude of effect for improving CAF in individuals with MetS.

CKD.QLD: establishment of a chronic kidney disease [CKD] registry in Queensland, Australia.

BACKGROUND: Chronic kidney disease [CKD] is recognised as a global public health problem. Until recently, the majority of information informing on CKD has been generated from renal registries reporting on patients with end-stage kidney disease [ESKD] and on renal replacement therapy [RRT]. There has been a paucity of information on pre-dialysis CKD cohorts, and many issues related to these poorly described populations are unresolved. To this end, international organizations have called for CKD surveillance systems across all countries. DESCRIPTION: In Australia, we have responded by developing the Chronic Kidney Disease in Queensland [CKD.QLD] with three main platforms consisting of CKD Registry, clinical trials and development of biobank. This registry which is the core component of CKD surveillance was conceptualized specifically for the pre-dialysis population in the public health system in Queensland, Australia. Recruitment started in May 2011, and to date the Registry has evolved as one of the largest CKD cohorts in the world with recruitment close to 7000 patients. The Registry has had many outcomes, including being the nidus for Australia's first National Health and Medical Research Council [NHMRC] CKD Centre of Research Excellence [CKD.CRE]. CONCLUSIONS: The Registry, with its linkage to Queensland Health datasets, is reporting, and is expected to continue generating, significant information on multiple aspects of CKD, its trajectory, management and patient outcomes. Intent of the CKD.CRE is to facilitate an expanded Registry network that has representation from health services, both public and private, across Australia.