Mid-thigh Cross-sectional Area Research Articles

Paper 31: Quantitative MRI of the Hamstring Muscles Ten Years After Autograft Hamstring ACLR

Paper 31: Quantitative MRI of the Hamstring Muscles Ten Years After Autograft Hamstring ACLR

Efficacy of interventions to alter measures of fat-free mass in people with COPD: a systematic review and meta-analysis.

Low fat-free mass (FFM) is linked to poor health outcomes in COPD, including impaired exercise tolerance and premature death. The aim of this systematic review was to synthesise evidence on the effectiveness of interventions for increasing FFM in COPD. Searches of electronic databases (MEDLINE, Cochrane Library, Embase, Web of Science, Scopus) and trial registers (ClinicalTrials.gov) were undertaken from inception to August 2022 for randomised studies of interventions assessing measures of FFM in COPD. The primary outcome was change in FFM (including derivatives). Secondary outcomes were adverse events, compliance and attrition. 99 studies (n=5138 people with COPD) of 11 intervention components, used alone or in combination, were included. Exercise training increased mid-thigh cross-sectional area (k=3, standardised mean difference (SMD) 1.04, 95% CI 0.02-2.06; p=0.04), but not FFM (k=4, SMD 0.03, 95% CI -0.18-0.24; p=0.75). Nutritional supplementation significantly increased FFM index (k=11, SMD 0.31, 95% CI 0.13-0.50; p<0.001), but not FFM (k=19, SMD 0.16, 95% CI -0.06-0.39; p=0.16). Combined exercise training and nutritional supplementation increased measures related to FFM in 67% of studies. Anabolic steroids increased FFM (k=4, SMD 0.98, 95% CI 0.24-1.72; p=0.009). Neuromuscular electrical stimulation increased measures related to FFM in 50% of studies. No interventions were more at risk of serious adverse events, low compliance or attrition. Exercise training and nutritional supplementation were not effective in isolation to increase FFM, but were for localised muscle and index measures, respectively. Combined, exercise and nutritional supplementation shows promise as a strategy to increase FFM in COPD. Anabolic steroids are efficacious for increasing FFM in COPD.

A randomised controlled trial assessing the potential of palmitoylethanolamide (PEA) to act as an adjuvant to resistance training in healthy adults: a study protocol

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) and analgesics are used frequently by athletes either prophylactically for the prevention of pain, or to accelerate recovery following an injury. However, these types of pain management strategies have been shown to inhibit signalling pathways (e.g., cyclooxygenase-2) that may hinder muscular adaptations such as hypertrophy and strength. Nutraceuticals such as palmitoylethanolamide (PEA) have analgesic properties that act via different mechanisms to NSAIDS/analgesics. Furthermore, PEA has been shown to have a positive effect on sleep and may contribute positively to muscle hypertrophy via PKB activation. Although PEA has not been widely studied in the athletic or recreationally active population, it may provide an alternative solution for pain management if it is found not to interfere with, or enhance training adaptations. Therefore, the study aim is to investigate the effects of daily PEA supplementation (Levagen + ®) with resistance training on lean body mass, strength, power and physical performance and outcomes of recovery (e.g., sleep) compared to placebo.MethodsThis double-blind, randomised controlled study will take place over an 11-week period (including 8-weeks of progressive resistance training). Participants for this study will be 18–35 years old, healthy active adults that are not resistance trained. Participants will attend a familiarisation (week 0), pre-testing (week 1) and final-testing (week 11). At the pre-testing and final-testing weeks, total lean body mass (dual-energy X-ray absorptiometry; DXA), total mid-thigh cross sectional area (pQCT), maximal muscular strength (1 repetition maximum bench press, isometric mid-thigh pull) and power (countermovement jump and bench throw) will be assessed. Additionally, circulating inflammatory cytokines and anabolic hormones, sleep quality and quantity (ActiGraph), pain and subjective wellbeing (questionnaires) will also be examined.DiscussionThis study is designed to investigate the effects that PEA may have on pre-to post intervention changes in total body and regional lean muscle mass, strength, power, sleep, subjective wellbeing, and pain associated with resistance training and menstruation compared with the placebo condition. Unlike other NSAIDs and analgesics, which may inhibit muscle protein synthesis and training adaptations, PEA which provides analgesia via alternative mechanisms may provide an alternative pain management solution. It is therefore important to determine if this analgesic compound interferes with or enhances training adaptations so that athletes and active individuals can make an informed decision on their pain management strategies.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

Extracellular matrix content and remodeling markers do not differ in college-aged men classified as higher and lower responders to resistance training.

We determined if skeletal muscle extracellular matrix (ECM) content and remodeling markers adapted with resistance training or were associated with hypertrophic outcomes. Thirty-eight untrained males (21 ± 3 yr) participated in whole body resistance training (10 wk, 2 × weekly). Participants completed testing [ultrasound, peripheral quantitative computed tomography (pQCT)] and donated a vastus lateralis (VL) biopsy 1 wk before training and 72 h following the last training bout. Higher responders (HR, n = 10) and lower responders (LR, n = 10) were stratified based on a composite score considering changes in pQCT-derived mid-thigh cross-sectional area (mCSA), ultrasound-derived VL thickness, and mean fiber cross-sectional area (fCSA). In all participants, training reduced matrix metalloprotease (MMP)-14 protein (P < 0.001) and increased satellite cell abundance (P < 0.001); however, VL fascial thickness, ECM protein content per myofiber, MMP-2/-9 protein content, tissue inhibitor of metalloproteinase (TIMP)-1/-2 protein content, collagen-1/-4 protein content, macrophage abundance, or fibroadipogenic progenitor cell abundance were not altered. Regarding responder analysis, MMP-14 exhibited an interaction (P = 0.007), and post hoc analysis revealed higher protein content in HR versus LR before training (P = 0.026) and a significant decrease from pre to posttraining in HR only (P = 0.002). In summary, basal skeletal muscle ECM markers are minimally affected with 10 wk of resistance training, and these findings could be related to not capturing more dynamic alterations in the assayed markers earlier in training. However, the downregulation in MMP-14 in college-aged men classified as HR is a novel finding and warrants continued investigation, and further research is needed to delineate muscle connective tissue strength attributes between HR and LR.NEW & NOTEWORTHY Although past studies have examined aspects of extracellular matrix remodeling in relation to mechanical overload or resistance training, this study serves to expand our knowledge on a multitude of extracellular matrix markers and whether these markers adapt to resistance training or are associated with differential hypertrophic responses.

Exercise and Creatine Supplementation to Augment the Adaptation of Exercise Training Among Breast Cancer Survivors Completing Chemotherapy: Protocol for an Open-label Randomized Controlled Trial (the THRIVE Study).

BackgroundIn breast cancer survivors, chemotherapy-induced muscle loss has been shown to be attenuated with structured resistance exercise. Creatine supplementation can increase bioenergetics in skeletal muscle, which helps to improve overall strength and endurance and reduce muscular fatigue. Therefore, we hypothesize that adding creatinine supplementation to exercise training will accelerate improvements in strength, endurance, and bioenergetics in breast cancer survivors.ObjectiveThe primary objective is to determine the effects of combining creatine supplementation with exercise on modulating strength and physical function in breast cancer survivors by comparing these effects to those of exercise alone. The secondary objectives are to determine if creatine supplementation and exercise can increase the intramuscular storage of creatine and improve body composition by comparing this intervention to exercise alone.MethodsWe aim to test our hypothesis by conducting an open-label randomized controlled trial of 30 breast cancer survivors who have completed chemotherapy within 6 months of enrollment. Eligible participants will be equally randomized (1:1) to either a creatine and exercise group or an exercise-only group for this 12-week intervention. Individuals who are randomized to receive creatine will be initially dosed at 20 g per day for 7 days to boost the availability of creatine systemically. Thereafter, the dose will be reduced to 5 g per day for maintenance throughout the duration of the 12-week protocol. All participants will engage in 3 center-based exercise sessions, which will involve completing 3 sets of 8 to 12 repetitions on chest press, leg press, seated row, shoulder press, leg extension, and leg curl machines. The primary outcomes will include changes in strength, body composition, and physical function in breast cancer survivors. The secondary outcomes will be intramuscular concentrations of creatine and adenosine triphosphate in the vastus lateralis, midthigh cross-sectional area, and quality of life.ResultsAs of October 2021, a total of 9 patients have been enrolled into the study. No unexpected adverse events have been reported.ConclusionsCreatine is being studied as a potential agent for improving strength, endurance, and bioenergetics in breast cancer survivors following chemotherapy. The findings from our trial may have future implications for supporting breast cancer survivors in reversing the muscle loss experienced during chemotherapy and improving their physical function and quality of life.Trial RegistrationClinicalTrials.gov NCT04207359; https://clinicaltrials.gov/ct2/show/NCT04207359International Registered Report Identifier (IRRID)PRR1-10.2196/26827

Utilization of Mid-Thigh Magnetic Resonance Imaging to Predict Lean Body Mass and Knee Extensor Strength in Obese Adults.

Purpose:To train and test a machine learning model to automatically measure mid-thigh muscle cross-sectional area (CSA) to provide rapid estimation of appendicular lean mass (ALM) and predict knee extensor torque of obese adults.Methods:Obese adults [body mass index (BMI) = 30–40 kg/m2, age = 30–50 years] were enrolled for this study. Participants received full-body dual-energy X-ray absorptiometry (DXA), mid-thigh MRI, and completed knee extensor and flexor torque assessments via isokinetic dynamometer. Manual segmentation of mid-thigh CSA was completed for all MRI scans. A convolutional neural network (CNN) was created based on the manual segmentation to develop automated quantification of mid-thigh CSA. Relationships were established between the automated CNN values to the manual CSA segmentation, ALM via DXA, knee extensor, and flexor torque.Results:A total of 47 obese patients were enrolled in this study. Agreement between the CNN-automated measures and manual segmentation of mid-thigh CSA was high (>0.90). Automated measures of mid-thigh CSA were strongly related to the leg lean mass (r = 0.86, p < 0.001) and ALM (r = 0.87, p < 0.001). Additionally, mid-thigh CSA was strongly related to knee extensor strength (r = 0.76, p < 0.001) and moderately related to knee flexor strength (r = 0.48, p = 0.002).Conclusion:CNN-measured mid-thigh CSA was accurate compared to the manual segmented values from the mid-thigh. These values were strongly predictive of clinical measures of ALM and knee extensor torque. Mid-thigh MRI may be utilized to accurately estimate clinical measures of lean mass and function in obese adults.

Sarcojoint®, the branched-chain amino acid-based supplement, plus resistance exercise improved muscle mass in adults aged 50years and older: A double-blinded randomized controlled trial.

Functional ability and intrinsic capacity are key elements of healthy aging, in which exercise and good nutrition play important roles. This 12-week double-blinded randomized controlled trial enrolled community-dwelling adults aged 50years and older to examine the effects of Sarcojoint®, a comprehensive formula for the musculoskeletal system, plus resistance exercise on muscle mass. This study intended to enroll 80 participants with a randomly selected subsample of 32 participants (16 from the intervention group and 16 from controls) for magnetic resonance imaging (MRI) to assess the cross-sectional area of the bilateral mid-thighs. The participants were then randomly assigned to the intervention group (Sarcojoint® 1 package twice a day) and control group (vitamin B as placebo) at a 1: 1 ratio. All the participants were required to undergo a regular exercise program (45min at the gym per week and two sessions of 30-min exercise at home). The data from 66 participants (68.1±7.1years and 16.7% males; intervention group: 32, control group: 34) were available for analysis. The whole study was pre-registered and data reporting followed Consolidated Standards of Reporting Trials with the primary endpoints of muscle mass, 30-s chair-rise test, and gait speed. Results of MRI were the subgroup analysis to examine muscle mass and intramuscular adiposity. The baseline characteristics of all the participants between groups were similar, as well as those of the MRI subgroups. Within-group comparisons showed that the intervention group, but not the control group, significantly reduced the total body fat percentage (34.3±5.5 vs. 35.0±5.4%, P=0.021). Serum vitamin D was increased in the intervention group (24.1±6.1 vs. 21.1±7.0ng/mL; P=0.025) and was reduced in the control group (18.0±5.2 vs. 20.2±5.8ng/mL; P=0.006). The physical performance tests of both groups were significantly improved. The between-group analysis showed no significant differences in 30-s chair stand test, handgrip strength and appendicular muscle mass. The sub-group analysis showed significant improvement in the serum levels of vitamin D (6.70±8.20 vs. -0.50±3.90ng/mL; P=0.001) and the mid-thigh cross-sectional area of the nondominant legs (165.4±291.4 vs. -61.1±195.0mm2; P=0.034) in the intervention group. In conclusion, Sarcojoint® plus resistance exercise significantly increased muscle mass and serum levels of vitamin D, but not significantly better in muscle strength and physical performance than controls. More investigations are needed to evaluate the long-term effects of Sarcojoint® on middle-aged and older adults.

Oral Nutritional Supplement with β-hydroxy-β-methylbutyrate (HMB) Improves Nutrition, Physical Performance and Ameliorates Intramuscular Adiposity in Pre-Frail Older Adults: A Randomized Controlled Trial.

Supplementation of high protein oral nutrition shakes supplemented with β-hydroxy-β-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons. This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity. Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs -22.9±309.1 mm2 for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. -0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. -1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m2, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (-0.38±1.21 vs. -0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (β=0.71, 95% C.I.0.09-1.33, P=0.026). The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.

Associations of Muscle Size and Density With Proximal Femur Bone in a Community Dwelling Older Population.

Background and Purpose: Muscle weakness and bone fragility are both associated with hip fracture. In general, muscle contractions create forces to the bone, and bone strength adapts to mechanical loading through changes in bone architecture and mass. However, the relationship between impairment of muscle and bone function remain unclear. In particular, the associations of muscle with properties of proximal femur cortical and trabecular bone are still not well understood. The aim of this study was to explore the associations of hip/thigh muscle density (CT attenuation value in Hounsfield units) and size with cortical and trabecular bone mineral density (BMD) of the proximal femur.Materials and Methods: Three-dimensional quantitative computed tomography (QCT) imaging of the lumber, hip and mid-thigh was performed in a total of 301 participants (mean age 68.4 ± 6.1 years, 194 women and 107 men) to derive areal BMD (aBMD) and volumetric BMD (vBMD). Handgrip strength (HGS) and the Timed Up and Go (TUG) test were also performed. From the CT images, cross-sectional area (CSA), and density were determined for the gluteus maximus muscle (G.MaxM), trunk muscle at the vertebrae L2 level, and mid-thigh muscle. Multivariate generalized linear models were applied to assess associations.Results: Total hip (TH) aBMD was associated significantly with G.MaxM CSA (men: P = 0.042; women: P < 0.001) and density (men: P = 0.012; women: P = 0.043). In women, 0.035 cm2 of mid-thigh CSA (95% CI, 0.014–0.057; P = 0.002) increased per SD increase in TH aBMD, but this significance was not observed in men (P = 0.095). Trunk muscle density and CSA were not associated with proximal femur BMD. The associations of hip/thigh muscle parameters with femoral neck BMD were weaker than those with trochanter and intertrochanter BMD. Furthermore, compared to muscle density, muscle CSA showed better associations with vBMD. G.MaxM CSA was associated with trochanter (TR) Cort. vBMD in men (β, 19.898; 95% CI, 0.924–38.871; P = 0.040) and in women (β, 15.426; 95% CI, 0.893–29.958; P = 0.038). Handgrip strength was only associated with TR aBMD (β, 0.038; 95% CI, 0.006–0.070; P = 0.019) and intertrochanter aBMD (β, 0.049; 95% CI, 0.009–0.090; P = 0.016) in men.Conclusions: We observed positive associations of the gluteus and thigh muscle size with proximal femur volumetric BMD. Specifically, the gluteus maximus muscle CSA was associated with trochanter cortical vBMD in both men and women.

The Impact of Malnutrition on Acute Muscle Wasting in Frail Older Hospitalized Patients.

Very little is known about the effect of malnutrition on short-term changes of body composition, particularly muscle, among older hospitalized patients. We sought to investigate the association of malnutrition as assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria with changes of thigh muscle mass and muscle strength among older patients during hospitalization. Forty-one patients (age range 66–97 years, 73% female) participated in this prospective longitudinal observational study. Nutritional status was evaluated using the GLIM criteria on admission and at discharge. Functional status and mid-thigh magnetic resonance imaging (MRI) measurements of cross-sectional area (CSA) were conducted on admission and before discharge. In all, 17% were malnourished and 83% had no malnutrition. Mean mid-thigh muscle CSA declined by 7.0 cm2 (−9%) in malnourished patients during hospitalization (p = 0.008) and remained unchanged among non-malnourished patients (−1%, p = 0.390). Mean mid-thigh CSA of subcutaneous and intermuscular fat did not change significantly during hospitalization in both groups. Malnourished subjects lost 10% of handgrip strength (−1.8 kg) and 12% of knee extension strength (−1.5 kg) during hospitalization. However, the magnitude of both changes did not differ between groups. In a stepwise multiple regression analysis, malnutrition and changes in body weight during hospitalization were the major independent risk factors for the reduction of muscle CSA. Malnutrition according to the GLIM criteria was significantly and independently associated with acute muscle wasting in frail older patients during 2-week hospitalization.

A Comparison of Techniques for Estimating and Detecting Changes in Skeletal Muscle Cross-Sectional Area

Muscle biopsy and subsequent histological analysis of muscle fibers is a criterion technique for determining hypertrophy of skeletal muscle in resistance- and endurance-trained individuals. However, due to the training necessary to complete the biopsy, and the invasive nature of the biopsy itself, alternative methods for depicting muscle fiber hypertrophy offer increased ability to gather data discerning skeletal muscle hypertrophy. Furthermore, such procedures require less training and are noninvasive. PURPOSE: This project sought to determine if estimated mid-thigh whole muscle cross-sectional area (CSA) is related to muscle fiber CSA from muscle biopsies. METHODS: Twenty-nine resistance-trained men (age: 21 ± 2 yrs, weight: 83.6 ± 11.0 kg, height: 178.7 ± 8.1 cm) underwent six weeks of total-body resistance training. Muscle biopsies were taken from the Vastus lateralis prior to and following training. Mid-thigh circumference and skinfold measurements (anterior, posterior, medial, and lateral) were used to estimate whole muscle mid-thigh cross-sectional area using the methods of Moritani and deVries. RESULTS: Whole-muscle CSA did not significantly increase from pre- (272.737 ± 37.401 cm) to post-training (277.286 ± 29.474 cm; p = 0.201). Muscle fiber CSA did not significantly increase from pre- (4068 ± 865 μm) to post-training (4221 ± 704 μm; p = 0.368). Additionally, pre muscle fiber CSA did not correlate to pre whole-muscle CSA (r = 0.029, p = 0.882). Also, Muscle fiber CSA percent change did not correlate with whole-muscle CSA percent change (r = -0.064, p = 0.741). CONCLUSION: Estimated whole-muscle CSA and muscle fiber CSA do not appear to correlate well. A lack of a relationship between the changes in these measurements following hypertrophy are puzzling and warrant further study.

Preliminary study of the anabolic/catabolic balance in patients with interstitial pulmonary fibrosis

RationaleIdiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressively fibrosing idiopathic interstitial pneumonias (IIP), as the disease progress, patients become severely limited in their activity. Hypoxemia is a common finding in IPF and may influence skeletal muscles homeostasis in several ways by decreasing anabolic hormone level [insulin like growth factor-1 (ILGF-1)] with as opposite effect on pro inflammatory cytokines as interleukin-6 (IL-6). It has been speculated that peripheral muscle force is inversely related to IL-6 and disturbed systemic levels of ILGF-1 may be important in the development of muscle weakness. ObjectivesTo assess the metabolic disturbance and its reflection on the muscular state in IPF patients. MethodsThe muscular state was assisted in 22 newly diagnosed IPF patients (not on steroids) (group 1) and 22 previously diagnosed IPF patients (on steroids) (group 2) by anthropometric measurements [Mid-thigh cross sectional area (MTCSA) and Mid- arm cross sectional area (MAC)], Body Mass Index (BMI) and measurements of serum levels of ILGF-1 and IL-6 by ELISA. Twenty two healthy subjects were selected as control (group 3). ResultsThere were no significant difference between the three groups as regards BMI, MTCSA and MAC. However, there was a highly significant decrease in the mean of serum IGF-1 level of group 1 in comparison to the control group (P<0.001). As regards, the mean of the serum IL-6 level there was no significant difference between the three groups. ConclusionsThe metabolic disturbance as regards the anabolic hormone level IGF-1 was the most affected in comparison to the other parameters.

Role of Mid Thigh Cross Sectional Area by Computed Tomography (MMTCSACT), C-Reactive Protein to Assess Effect of Pulmonary Rehabilitation (PR) In Interstitial Lung Diseases (ILDs)

Role of Mid Thigh Cross Sectional Area by Computed Tomography (MMTCSACT), C-Reactive Protein to Assess Effect of Pulmonary Rehabilitation (PR) In Interstitial Lung Diseases (ILDs)

Essential amino acids to treat sarcopenia in patients with COPD?

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Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD.

Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population.In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190– -30 HU; skeletal muscle -29–150 HU.Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72–0.95).Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes.

Increased Skeletal Muscle 11βHSD1 mRNA Is Associated with Lower Muscle Strength in Ageing

BackgroundSarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle.MethodsThere were 82 participants; group 1 comprised 33 older men (mean age 70.2years, SD 4.4) and 19 younger men (22.2years, 1.7) and group 2 comprised 16 older men (79.1years, 3.4) and 14 older women (80.1years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size.ResultsMuscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size.ConclusionAlthough circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia.

Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine?

Quadriceps muscle dysfunction is common in COPD. Determining, and, if possible, predicting quadriceps phenotype in COPD is important for patient stratification for therapeutic trials. In biopsies from 114 COPD patients and 30 controls, we measured fiber size and proportion and assessed the relationship with quadriceps function (strength and endurance), clinical phenotype (lung function, physical activity, fat-free mass) and exercise performance. In a subset (n = 40) we measured muscle mid-thigh cross-sectional area by computed tomography. Normal ranges for fiber proportions and fiber cross-sectional area were defined from controls; we found isolated fiber shift in 31% of patients, isolated fiber (predominantly type II) atrophy in 20%, both shift and atrophy in 25%, and normal fiber parameters in 24%. Clinical parameters related poorly to muscle biopsy appearances. Quadriceps morphology is heterogeneous in COPD and cannot be predicted without biopsy, underlining the need for biomarkers.

Changes in Insulin Resistance and HbA1c Are Related to Exercise-Mediated Changes in Body Composition in Older Adults With Type 2 Diabetes

OBJECTIVETo investigate changes in body composition after 12 months of high-intensity progressive resistance training (PRT) in relation to changes in insulin resistance (IR) or glucose homeostasis in older adults with type 2 diabetes.RESEARCH DESIGN AND METHODSOne-hundred three participants were randomized to receive either PRT or sham exercise 3 days per week for 12 months. Homeostasis model assessment 2 of insulin resistance (HOMA2-IR) and glycosylated hemoglobin (HbA1c) were used as indices of IR and glucose homeostasis. Skeletal muscle mass (SkMM) and total fat mass were assessed using bioelectrical impedance. Visceral adipose tissue, mid-thigh cross-sectional area, and mid-thigh muscle attenuation were quantified using computed tomography.RESULTSWithin the PRT group, changes in HOMA2-IR were associated with changes in SkMM (r = −0.38; P = 0.04) and fat mass (r = 0.42; P = 0.02). Changes in visceral adipose tissue tended to be related to changes in HOMA2-IR (r = 0.35; P = 0.07). Changes in HbA1c were related to changes in mid-thigh muscle attenuation (r = 0.52; P = 0.001). None of these relationships were present in the sham group (P > 0.05). Using ANCOVA models, participants in the PRT group who had increased SkMM had decreased HOMA2-IR (P = 0.05) and HbA1c (P = 0.09) compared with those in the PRT group who lost SkMM. Increases in SkMM in the PRT group decreased HOMA2-IR (P = 0.07) and HbA1c (P < 0.05) compared with those who had increased SkMM in the sham group.CONCLUSIONSImprovements in metabolic health in older adults with type 2 diabetes were mediated through improvements in body composition only if they were achieved through high-intensity PRT.

Effects of nutritional supplementation combined with conventional pulmonary rehabilitation in muscle‐wasted chronic obstructive pulmonary disease: A prospective, randomized and controlled study

Nutritional depletion in chronic obstructive pulmonary disease (COPD) adversely affects health status and mortality. We aimed to evaluate the effects of nutritional supplementation (NS) with pulmonary rehabilitation (PR) on body composition, mid-thigh cross-sectional area (CSA), dyspnoea, exercise capacity, health-related quality of life, anxiety and depression in advanced COPD patients. Forty-six patients were randomized to PR and nutritional support (PRNS), PR or the control group. Dyspnoea was measured with Medical Research Council and BORG scales. Exercise capacity was measured through 6-min walk test and shuttle tests; health-related quality of life was assessed with St. George's Respiratory Questionnaire. Psychological status was measured with Hospital Anxiety and Depression Scale. Body weight and body mass indexes (BMI) were also evaluated. Fat-free mass was measured through bioelectrical impedance analyser. The CSA of quadriceps was calculated in mid-level of the thigh with magnetic resonance imaging. Dyspnoea and total scores of St. George's Respiratory Questionnaire improved in both groups (P < 0.05). Six-minute walk test and incremental shuttle walk test distances in PRNS and PR patients increased significantly as (62.6 ± 42.4 m, 43.3 ± 59.2 m, both P = 0.001; and 63.3 ± 70.1 m and 69.3 ± 69.7 m, both P = 0.001). Although anxiety improved in both groups (P < 0.05), there was no change in depression. Body weight, BMI and fat-free mass index (FFMI) (1.1 ± 0.9 kg, 0.2 ± 1.4 kg/m(2) and 0.6 ± 0.5 kg/m(2), P < 0.05) in PRNS, whereas body weight and FFMI (0.6 ± 0.7 kg, 0.1 ± 0.6 kg/m(2) P < 0.05) increased in PR after the intervention. There was a significant increase in mid-thigh CSA (2.5 ± 4.1 cm(2)) only in PRNS (P = 0.04). The combination of NS with PR resulted in improvements particularly in lean body mass and mid-thigh CSA. This study suggests combining NS with PR in reversing weight loss and muscle wasting in COPD.

Quadriceps bulk and strength and effect of its training in patients with moderate to severe chronic obstructive pulmonary disease

BackgroundSkeletal muscle dysfunction is one of the important systemic manifestations of chronic obstructive pulmonary disease (COPD) and is associated with mortality in those patients thus quantifying its bulk and strength is of great clinical interest and of particular value. ObjectiveEvaluation of quadriceps muscle bulk & strength in patients with moderate to severe stable COPD compared with normal healthy subjects and the effect of progressive resistant exercise program for 12weeks on quadriceps muscle strength and exercise capacity. Subjects and methodsForty patients with moderate to severe stable COPD they were 26 males and 14 females. Ten healthy subjects with the same age and sex were also included as controls. All patients and controls were evaluated at baseline for quadriceps maximal voluntary contraction (QMVC), exercise capacity, the mid – thigh cross sectional area (MTCSA) and spirometric pulmonary functions then patients were classified into 2 groups only group one performed the progressive resistant exercise program for 12weeks then reassessment of both group were done. ResultsPatients and controls were matched as regard age, weight, height and body mass index. There was significant difference between patients and control in QMVC, MTCSA, and FFM after training for 12weeks only group one had significant difference in QMVC, MTCSA and FFM/Kg in comparison to the baseline, while there was no significant difference as regard the pulmonary functions. Also there was significant difference between group 1 and 2 after 12weeks in QQMVC, MTCSA and FFM/kg. ConclusionWe have collected evidence indicating that both bulk and strength of quadriceps muscles in particular were reduced in patients with COPD compared with normal controls and these changes can be improved with progressive training without change in pulmonary functions.