Cardiometabolic and immune response to exercise training in patients with metabolic syndrome: retrospective analysis of two randomized clinical trials.

Background: Metabolic syndrome (MetS) is defined by the presence of central obesity plus ≥two metabolic/cardiovascular risk factors (RF), with inflammation being a major disease-driving mechanism. Structured endurance exercise training (ET) may positively affect these traits, as well as cardiorespiratory fitness (V̇O2peak). Aims: We explore individual ET-mediated improvements of MetS-associated RF in relation to improvements in V̇O2peak and inflammatory profile. Methods: MetS patients from two randomized controlled trials, ExMET (n = 24) and OptimEx (n = 34), had performed 4- or 3-months supervised ET programs according to the respective trial protocol. V̇O2peak, MetS-defining RFs (both RCTs), broad blood leukocyte profile, cytokines and plasma proteins (ExMET only) were assessed at baseline and follow-up. Intra-individual changes in RFs were analysed for both trials separately using non-parametric approaches. Associations between changes in each RF over the exercise period (n-fold of baseline values) were correlated using a non-parametrical approach (Spearman). RF clustering was explored by uniform manifold approximation and projection (UMAP) and changes in RF depending on other RF or exercise parameters were explored by recursive partitioning. Results: Four months of ET reduced circulating leukocyte counts (63.5% of baseline, P = 8.0e-6), especially effector subtypes. ET response of MetS-associated RFs differed depending on patients' individual RF constellation, but was not associated with individual change in V̇O2peak. Blood pressure lowering depended on cumulative exercise duration (ExMET: ≥102 min per week; OptimEx-MetS: ≥38 min per session) and baseline triglyceride levels (ExMET: <150 mg/dl; OptimEx-MetS: <174.8 mg/dl). Neuropilin-1 plasma levels were inversely associated with fasting plasma triglycerides (R: -0.4, P = 0.004) and changes of both parameters during the ET phase were inversely correlated (R: -0.7, P = 0.0001). Conclusions: ET significantly lowered effector leukocyte blood counts. The improvement of MetS-associated cardiovascular RFs depended on individual basal RF profile and exercise duration but was not associated with exercise-mediated increase in V̇O2peak. Neuropilin-1 may be linked to exercise-mediated triglyceride lowering.

Influence of a 7-day Transalpine Trail Run on cardiac biomarkers and myocardial function.

Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7-day trail-running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs-TnT, NT-proBNP, and suppression of tumorigenicity-2 protein (ST2)) at baseline, after each stage and 24-48 h post-race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT-proBNP increased significantly (3.6-fold, p = 0.009) during the first stage and continued to increase during the race. Hs-TnT revealed an incremental trend during the first day (2.7-fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post-race. NT-proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = -0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post-race. In summary, this study shows that prolonged, repetitive, high-volume exercise induced a transient, significant increase in NT-proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment.

Cardiovascular risk factors, exercise capacity and health literacy in patients with chronic ischaemic heart disease and type 2 diabetes mellitus in Germany: Baseline characteristics of the Lifestyle Intervention in Chronic Ischaemic Heart Disease and Type 2 Diabetes study.

BACKGROUND: Lifestyle interventions are a cornerstone in the treatment of chronic ischaemic heart disease (CIHD) and type 2 diabetes mellitus (T2DM). This study aimed at identifying differences in clinical characteristics between categories of the common lifestyle intervention targets BMI, exercise capacity (peak V̇O2) and health literacy (HL). METHODS: Cross-sectional baseline characteristics of patients enrolled in the LeIKD trial (Clinicaltrials.gov NCT03835923) are presented in total, grouped by BMI, %-predicted peak V̇O2 and HL (HLS-EU-Q16), and compared to other clinical trials with similar populations. RESULTS: Among 499 patients (68.3±7.7 years; 16.2% female; HbA1c, 6.9±0.9%), baseline characteristics were similar to other trials and revealed insufficient treatment of several risk factors (LDL-C 92±34 mg/dl; BMI, 30.1±4.8 kg/m2; 69.6% with peak V̇O2<90% predicted). Patients with lower peak V̇O2 showed significantly higher (p < 0.05) CIHD and T2DM disease severity (HbA1c, CIHD symptoms, coronary artery bypass graft). Obese patients had a significantly higher prevalence of hypertension and higher triglyceride levels, whereas in patients with low HL both quality of life components (physical, mental) were significantly reduced. CONCLUSIONS: In patients with CIHD and T2DM, peak V̇O2, BMI and HL are important indicators of disease severity, risk factor burden and quality of life, which reinforces the relevance of lifestyle interventions.

Cluster Randomized Controlled Trial on the Effects of 12 Months of Combined Exercise Training during Hemodialysis in Patients with Chronic Kidney Disease-Study Protocol of the Dialysis Training Therapy (DiaTT) Trial.

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months' intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology.

Lifestyle Intervention in Chronic Ischaemic Heart Disease and Type 2 Diabetes (the LeIKD study): study protocol of a prospective, multicentre, randomised, controlled trial.

INTRODUCTION: Guidelines recommend lifestyle intervention in chronic ischaemic heart disease (CIHD) and type 2 diabetes mellitus (T2DM). However, evidence from randomised controlled trials is scarce in patients with combined entities. METHODS AND ANALYSIS: The Lifestyle Intervention in Chronic Ischaemic Heart Disease and Type 2 Diabetes (LeIKD) trial is a prospective, multicentre study that will randomise (1:1) patients with CIHD (ICD-10: I20-I25) and T2DM (ICD-10: E11) from one health insurance company into a lifestyle intervention (LS) or usual care (UC). Active LS consists of an individual combined exercise programme of strength and endurance training and nutritional counselling with regular feedback for 6 months. Intervention is supported by telemedicine. Follow-up without individualised feedback will continue for 6 months. The study aims to investigate whether an individualised telemedical supported LS intervention is superior to UC in improving cardiovascular risk factors, physical activity, quality of life, health literacy, major cardiovascular events and health economics in patients with both CIHD and T2DM. Primary endpoint is the change in HbA1c from baseline to 6 months. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee of the Technical University of Munich (registration number: 144/18-S) and at each study site. The study will be conducted according to the World Medical Association Declaration of Helsinki, and results will be published in articles and reports. It is funded by the Federal Joint Committee (www.innovationsfonds.g-ba.de), reference number 01NVF17015, which has no impact on data collection, analysis or interpretation. Dissemination is independent of the funding source. TRIAL REGISTRATION NUMBER: Clinical trials.gov identifier: NCT03835923. German registry for clinical studies (DRKS): DRKS00015140.

The Effect of Exercise Intensity and Volume on Metabolic Phenotype in Patients with Metabolic Syndrome: A Randomized Controlled Trial.

Background: Moderate intensity continuous training (MICT) ameliorates dysmetabolism in patients with metabolic syndrome (MetS). The impact of low- (1HIIT) versus high-volume high-intensity interval training (4HIIT) versus MICT on central adiposity, insulin resistance, and atherogenic dyslipidemia in patients with MetS has not yet been reported. Methods: Twenty-nine patients with MetS according to International Diabetes Federation criteria (nine females, age 61 ± 5 years, body mass index 31.1 ± 3.7 kg/m2, waist circumference (WC) ♀ 102.2 ± 10.6 cm, ♂ 108.5 ± 8.6 cm) were randomized (1:1:1) to 16 weeks of (1) MICT (5 × 30 min/week, 35%-50% heart rate reserve (HRR), (2) 1HIIT (3 × 17 min/week incl. 4 min @80%-90% HRR), and (3) 4HIIT (3 × 38 min/week incl. 4 × 4 min @80%-90% HRR). Peak oxygen uptake (V̇O2peak), WC and anthropometric/metabolic indices indicative of MetS, fasting glucose/insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), dyslipidemia, and respiratory exchange ratio (RER) at warm-up were quantified at baseline and study completion. Analysis of variance and paired t tests were used for statistical analysis. Analyses were performed after checking for parametric distribution. Results: There were no significant differences between groups in waist-to-height ratio (♀: Δ -0.10 ± -0.05, ♂: Δ -0.08 ± -0.06, P = 0.916), WC (♀: Δ -1.4 ± -0.1 cm, ♂: Δ 0.1 ± 0.9 cm, P = 0.590), fasting glucose (Δ -1.18 ± 16.7 µU/mL, P = 0.773), fasting insulin (Δ 0.76 ± 13.4 µU/mL, P = 0.509), HOMA-IR (Δ 0.55 ± 4.1, P = 0.158), atherogenic dyslipidemia [triglycerides (TAG) Δ -10.1 ± 46.9 mg/dL, P = 0.468, high-density lipoprotein cholesterol (HDL-C) Δ 1.5 ± 5.4, P = 0.665, TAG/HDL-C -0.19 ± 1.3, P = 0.502], V̇O2peak (P = 0.999), or RER (P = 0.842). In the entire group, waist-to-height-ratio and V̇O2peak significantly improved by a clinically meaningful amount (Δ 2.7 ± 0.9 mL/min/kg; P < 0.001) and RER at warm-up significantly decreased (Δ -0.03 ± 0.06, P = 0.039). Conclusion: In patients with MetS, there was no significant difference between HIIT, irrespective of volume, to MICT for improving exercise capacity or metabolic health.