Kenneth Verboven

High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial.

Introduction Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS). The impact of high intensity exercise remains unknown. Methods Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11) and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12) or high intensity continuous cardiovascular training (HCTR, n = 11), both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA) and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks. Results Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21±7%, HCTR: +23±5%). Furthermore, fiber type I CSA increased in HCTR (+29±6%), whereas type II (+23±7%) and IIa (+23±6%,) CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13±7% and +45±20%) and body fat percentage tended to decrease (HITR: -3.9±2.0% and HCTR: -2.5±1.2%). Furthermore, endurance capacity (Wmax +21±4%, time to exhaustion +24±5%, VO2max +17±5%) and lean tissue mass (+1.4±0.5%) only increased in HITR. Finally self-reported physical activity levels increased 73±19% and 86±27% in HCTR and HITR, respectively. Conclusion High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS. Trial Registration ClinicalTrials.gov NCT01845896

Slowed Exercise-Onset Vo2 Kinetics During Submaximal Endurance Exercise in Subjects With Multiple Sclerosis:

Background. Low physical activity levels in persons with multiple sclerosis (MS) may reduce skeletal muscle oxidative capacity. Rehabilitation strategies might be altered by a measure of capacity that did not require invasive techniques or maximal exercise testing. For this purpose, we measured exercise onset and offset oxygen uptake (Vo2) kinetics during endurance exercise. Objective. This study compared exercise-onset and -offset Vo2 kinetics in mildly affected persons with MS with healthy matched participants. Methods. From 38 MS patients who had a mean Expanded Disability Status Scale of 3.1 and 16 healthy participants, exercise-onset and -offset Vo2 kinetics (mean response time [MRT]) were determined during two 6-minute submaximal bouts of exercise separated by a 6-minute recovery interval. Blood lactate, heart rate, expiratory volume, and Borg ratings of perceived exertion were assessed during exercise and compared between groups. Relationships between clinical characteristics and MRT were assessed. Results. During exercise, blood lactate, heart rate, and expiratory volume did not differ between groups (P > .05), but exercise-onset MRT was significantly slower in MS versus healthy participants (P = .007). Exercise-onset MRT was independently related to having MS (P = .02). Exercise-offset MRT was not different between groups or was independently related to having MS (P > .05). No independent relationships between clinical characteristics of MS and exercise-onset or -offset MRT were found. Conclusions. Exercise-onset Vo2 kinetics during submaximal endurance exercise are significantly slowed in mildly disabled persons with MS, suggesting low skeletal muscle oxidative capacity. Using mean response time testing, rehabilitation interventions for this reduction in exercise capacity can be assessed and targeted.

Impact of 24 Weeks of Resistance and Endurance Exercise on Glucose Tolerance in Persons with Multiple Sclerosis.

BackgroundRecently, the authors reported an elevated prevalence of impaired glucose tolerance in individuals with multiple sclerosis (MS), compared with matched healthy controls, indicating metabolic defects that may increase comorbidity. MS also leads to a more inactive lifestyle, increasing the likelihood to develop fat accumulation, muscle wasting/weakness, and exercise intolerance. In other populations, these health complications can partly be reversed by physical exercise. ObjectiveThe aim of this study was to determine the impact of a mild-to-moderate–intensity exercise program on glucose tolerance, ranging between normal and impaired, in persons with MS. DesignPersons with MS (mean expanded disability status scale, 3.3 ± 0.2; mean age, 48 ± 15 yrs) were randomized to an exercise group (n = 29) or a nonexercise control group (n = 15). Glucose tolerance, as well as muscle strength, exercise tolerance, and body composition to validate the applied exercise program, was determined in both groups at baseline and after 6, 12, and 24 wks of mild-to-moderate–intensity combined endurance and resistance training. ResultsNo effects on blood glucose and serum insulin were detected. However, 6 mos of exercise improved muscle strength, exercise tolerance, and lean tissue mass within the intervention group as compared with baseline. In the control group, no changes were detected. ConclusionTwenty-four weeks of mild-to-moderate–intensity combined endurance and resistance training was not able to improve glycemic control in this cohort of persons with MS. Future research is warranted to investigate the influence of higher exercise intensities on glucose tolerance, in an attempt to remediate metabolic deficits and to decrease the prevalence of comorbidities in MS.

Circulating classical monocytes are associated with CD11c+ macrophages in human visceral adipose tissue

Immune cell accumulation in adipose tissue (AT) is associated with the development of AT inflammation, resulting in metabolic dysfunction. Circulating immune cell patterns may reflect immune cell accumulation in expanding AT. However, data linking human leukocytes in blood and AT is lacking. We investigated whether blood immune cell populations are associated with their counterparts in subcutaneous (scAT) or visceral AT (vAT). Flow cytometry was performed on blood, scAT and vAT from 16 lean and 29 obese men. Circulating natural killer (NK)-cells, classical monocytes and nonclassical monocytes were higher in obese individuals. vAT, but not scAT, of obese individuals contained more inflammatory CD11c+ “M1” macrophages and NK cells compared to lean individuals. Blood classical monocytes were associated with CD11c+ macrophages in vAT but not scAT. This association was unrelated to expression of the adhesion molecules CD11b and CD11c or of the chemokine receptor CX3CR1 on these monocytes. Other AT immune cells were not associated with their respective counterparts in blood. Finally, CD11c+ macrophages and CD4+ T-cells in vAT were associated with their counterparts in scAT. In conclusion, blood classical monocytes reflect CD11c+ macrophages in vAT.

High Intensity Aerobic and Resistance Exercise Can Improve Glucose Tolerance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.

Introduction The prevalence of impaired glucose tolerance (IGT) is higher in persons with multiple sclerosis (MS) compared to healthy controls, indicating metabolic deficits that may increase comorbidity. In other populations, IGT can, at least partly, be reversed by intense physical exercise, but this is never investigated before in MS. Aim To investigate the effect of high intensity aerobic and resistance training on glucose tolerance and skeletal muscle GLUT4 content in MS. Methods Thirty-four persons with MS (aged 45 ± 3 years, EDSS 2.5 ± 1.07) were randomized into three groups, including a (1) sedentary control group (SED, n = 11), (2) 12-week high intensity interval plus resistance training group (HITR, n = 12), or (3) 12-week high intensity continuous aerobic training plus resistance training group (HCTR, n = 11). Before and after 12 weeks, glucose tolerance and skeletal muscle GLUT4 content were determined by an oral glucose tolerance test and analysis of a m.vastus lateralis biopsy, respectively. Results There were no significant changes for subjects of SED. From pre- to post-intervention, total area under the glucose curve (tAUC) decreased significantly in both HITR (−6.9 ± 6.2%) and HCTR (−11.0 ± 7.7%) (P < 0.05). Insulin tAUC decreased (−12.3 ± 14.7%) within HCTR and muscle GLUT4 content increased (+6.6 ± 4.5%) in HITR. Conclusion Twelve weeks of high intensity aerobic exercise in combination with resistance training improved glucose tolerance in persons with MS.

Altered signaling for mitochondrial and myofibrillar biogenesis in skeletal muscles of patients with multiple sclerosis

Patients with multiple sclerosis (pwMS) experience muscle weakness and lowered muscle oxidative capacity. To explore the etiology for the development of such muscle phenotype we studied skeletal muscle adenosine monophosphate (AMP)-activated protein kinase phosphorylation (phospho-AMPKα, governing mitochondrial biogenesis) and mammalian target of rapamycin phosphorylation (phospho-mTOR, governing myofibrillar biogenesis) in pwMS. After assessment of body composition, muscle strength, exercise tolerance, and muscle fiber type, muscle phospho-AMPKα and phospho-mTOR were assessed in 14 pwMS and 10 healthy controls (part 1). Next, an endurance exercise bout was executed by 9 pwMS and 7 healthy subjects, with assessment of changes in muscle phospho-AMPKα and phospho-mTOR (part 2). Increased basal muscle phospho-AMPKα and phospho-mTOR were present in MS (P < 0.01) and independently related to MS. Correlations between muscle phospho-AMPKα or phospho-mTOR and whole-body fat mass, peak oxygen uptake, and expanded disability status scale (P < 0.05) were found. After endurance exercise muscle phospho-AMPKα and phospho-mTOR remained increased in pwMS (P < 0.01). Muscle signaling cascades for mitochondrial and myofibrillar biogenesis are altered in MS and related to the impairment and disability level. These findings indicate a link between muscle signaling cascades and the level of disability and impairment, and thus may open a new area for the development of novel therapies for peripheral muscle impairment in MS.

Natriuretic peptides in the control of lipid metabolism and insulin sensitivity

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in human substrate and energy metabolism, thereby connecting the heart with several insulin‐sensitive organs like adipose tissue, skeletal muscle and liver. Obesity may be associated with an impaired regulation of the natriuretic peptide system, also indicated as a natriuretic handicap. Evidence points towards a contribution of this natriuretic handicap to the development of obesity, type 2 diabetes mellitus and cardiometabolic complications, although the causal relationship is not fully understood. Nevertheless, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on current literature regarding the metabolic roles of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Furthermore, it will be discussed how exercise and lifestyle intervention may modulate the natriuretic peptide‐related metabolic effects.

Elevated cardiovascular risk factors in multiple sclerosis

BACKGROUND Multiple sclerosis (MS) is associated with elevated cardiovascular mortality. To prevent this a better understanding of their CVD risk factors and interrelations is necessary. METHODS MS patients (n = 52) and healthy controls (HC, n = 24) were matched for age, height, weight, body mass index and physical activity. Body composition, resting blood pressure (BP), resting heart rate (HR), glucose tolerance, HbA1c, blood lipids (HDL, LDL, total cholesterol, triglyceride concentrations) and c-reactive protein concentrations were analyzed. Regression analyses identified independent CVD risk factors and their interrelations in MS. RESULTS In MS and compared to HC, fat mass (25.1 ± 1.2kg vs. 17.9 ± 1kg), fat percentage (33.8 ± 1.2% vs. 28.4 ± 1.5%), systolic (130 ± 1.8mmHg vs. 120 ± 2.9mmHg) and diastolic (79 ± 1.1mmHg vs. 71 ± 1.9mmHg) BP, resting HR (72 ± 1.4bpm vs. 60 ± 2bpm), blood triglycerides (113.8 ± 8.6mg/dl vs. 98.2 ± 17.4mg/dl), fasting (13.5 ± 2.9mU/l vs. 7.2 ± 0.8mU/l) and 2h insulin (71.9 ± 12.5mU/l vs. 35.8 ± 8.1mU/l), 2h glucose (6.3 ± 0.5mmol/l vs. 4.8 ± 0.5mmol/l) and HOMA index (3.7 ± 1.1 vs. 1.7 ± 0.2) were significantly (p < 0.05) elevated. Total cholesterol, blood HDL and LDL concentrations did nog differ between groups (p < 0.05). Regression analyses indicated that MS is independently associated with elevated fat mass/percentage, systolic and diastolic BP and HR and in MS fat mass appears to be an independent contributor of the other measured CVD risk factors in MS. CONCLUSION Persons with MS have an increased risk for CVD and fat mass appears to be an important risk factor. Therefore, normalizing whole body fat should be an essential part of MS treatment.

Exercise improves cardiac function and attenuates insulin resistance in Dahl salt-sensitive rats

BACKGROUND The development of heart failure (HF) secondary to hypertension is a complex process related to a series of physiological and molecular factors including glucose dysregulation. The overall objective of this study was to investigate whether exercise training could improve cardiac function and insulin resistance in a rat model of hypertensive HF. METHODS Seven week old Dahl salt-sensitive rats received either 8% NaCl (n = 30) or 0.3% NaCl (n = 18) diet. After a 5-week diet, animals were randomly assigned to exercise training (treadmill running at 18 m/min, 5% inclination for 60 min, 5 days/week) or kept sedentary for 6 additional weeks. 2D echocardiography was used to calculate left ventricular (LV) dimensions, volumes and global functional parameters. LV global deformation parameters were measured with speckle tracking echocardiography. Insulin resistance was assessed using 1h oral glucose tolerance testing. RESULTS High salt diet led to cardiac hypertrophy and HF, characterized by increased wall thicknesses and LV volumes as well as reduced deformation parameters. In addition, high salt diet was associated with the development of insulin resistance. Exercise training improved cardiac function, reduced the extent of interstitial fibrosis and reduced insulin levels 60 min post-glucose administration. CONCLUSIONS Even if not fully reversed, exercise training in HF animals improved cardiac function and insulin resistance. Adjusted modalities of exercise training might offer new insights not only as a preventive strategy, but also as a treatment for HF patients.

Magnitude of muscle wasting early after on‐pump coronary artery bypass graft surgery and exploration of aetiology

What is the central question of this study? It remains uncertain whether significant fat‐free mass wasting occurs early after coronary artery bypass graft surgery, and the aetiology of this wasting in these particular conditions is unexplored. What is the main finding and its importance? Significant fat‐free mass wasting is present after coronary artery bypass graft surgery, and this wasting effect is greater in younger patients and in patients with greater increments in blood cortisol‐to‐testosterone ratios after surgery.