Douglas E. Long

A new BIA equation estimating the body composition of young children.

Bioelectric impedance analyses (BIA) provides a valid and reliable measure of body composition in field, clinical, and research settings if standard protocol procedures are followed, and population‐specific equations are available and utilized. The objective of this study was to create and cross‐validate a new BIA body composition equation with representative healthy weight (HW), overweight (OW), and obese (OB) young children. Participants were 436 children who were 5–11 years of age. Dual‐energy absorptiometry fat‐free mass (FFM) was used as the criterion measure and a single frequency tetra‐polar BIA device was used to create the new BIA equation. The new BIA equation explained 95.2% of the variance in FFM with no statistical shrinkage upon cross‐validation. The use of this equation may help to identify effective intervention strategies to prevent or combat childhood obesity, and may assist in additional conditions or treatments where information concerning body composition measures would provide greater accuracy and sensitivity measures for preventing or combating disease.

Association of fibromyalgia with altered skeletal muscle characteristics which may contribute to postexertional fatigue in postmenopausal women

OBJECTIVE To identify muscle physiologic properties that may contribute to postexertional fatigue and malaise in women with fibromyalgia (FM). METHODS Healthy postmenopausal women with (n = 11) and without (n = 11) FM, ages 51-70 years, participated in this study. Physical characteristics and responses to self-reported questionnaires were evaluated. Strength loss and tissue oxygenation in response to a fatiguing exercise protocol were used to quantify fatigability and the local muscle hemodynamic profile. Muscle biopsies were performed to assess between-group differences in baseline muscle properties using histochemical, immunohistochemical, and electron microscopic analyses. RESULTS There was no significant difference between healthy controls and FM patients in muscle fatigue in response to exercise. However, self-reported fatigue and pain were correlated with prolonged loss of strength following 12 minutes of recovery in patients with FM. Although there was no difference in percent succinate dehydrogenase (SDH)-positive (type I) and SDH-negative (type II) fibers or in mean fiber cross-sectional area between groups, FM patients exhibited greater variability in fiber size and altered fiber size distribution. In healthy controls only, fatigue resistance was strongly correlated with the size of SDH-positive fibers and hemoglobin oxygenation. In contrast, FM patients with the highest percentage of SDH-positive fibers recovered strength most effectively, and this was correlated with capillary density. However, overall, capillary density was lower in the FM group. CONCLUSION Peripheral mechanisms, i.e., altered muscle fiber size distribution and decreased capillary density, may contribute to postexertional fatigue in FM. Understanding of these defects in fibromyalgic muscle may provide valuable insight with regard to treatment.

Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia.

IntroductionWomen with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.MethodsFourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value.ResultsSubjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion.ConclusionsOur results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle.

Insulin‐resistant subjects have normal angiogenic response to aerobic exercise training in skeletal muscle, but not in adipose tissue

Reduced vessel density in adipose tissue and skeletal muscle is associated with obesity and may result in decreased perfusion, decreased oxygen consumption, and insulin resistance. In the presence of VEGFA, Angiopoietin‐2 (Angpt2) and Angiopoietin‐1 (Angpt1) are central determinants of angiogenesis, with greater Angpt2:Angpt1 ratios promoting angiogenesis. In skeletal muscle, exercise training stimulates angiogenesis and modulates transcription of VEGFA, Angpt1, and Angpt2. However, it remains unknown whether exercise training stimulates vessel growth in human adipose tissue, and it remains unknown whether adipose angiogenesis is mediated by angiopoietin signaling. We sought to determine whether insulin‐resistant subjects would display an impaired angiogenic response to aerobic exercise training. Insulin‐sensitive (IS, N = 12) and insulin‐resistant (IR, N = 14) subjects had subcutaneous adipose and muscle (vastus lateralis) biopsies before and after 12 weeks of cycle ergometer training. In both tissues, we measured vessels and expression of pro‐angiogenic genes. Exercise training did not increase insulin sensitivity in IR Subjects. In skeletal muscle, training resulted in increased vessels/muscle fiber and increased Angpt2:Angpt1 ratio in both IR and IS subjects. However, in adipose, exercise training only induced angiogenesis in IS subjects, likely due to chronic suppression of VEGFA expression in IR subjects. These results indicate that skeletal muscle of IR subjects exhibits a normal angiogenic response to exercise training. However, the same training regimen is insufficient to induce angiogenesis in adipose tissue of IR subjects, which may help to explain why we did not observe improved insulin sensitivity following aerobic training.

Does computed tomography-based muscle density predict muscle function and health-related quality of life in patients with idiopathic inflammatory myopathies?

To investigate the association of low‐density (lipid‐rich) muscle measured by computed tomography (CT) with skeletal muscle function and health‐related quality of life in idiopathic inflammatory myopathies (IIMs).

Human Body Composition and Immunity: Visceral Adipose Tissue Produces IL-15 and Muscle Strength Inversely Correlates with NK Cell Function in Elderly Humans

Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) are sources of IL-15 and IL-15 Rα, and (2) whether any of these tissues correlate with NK cell activity in elderly humans. We first investigated IL-15 and IL-15Rα RNA expression in paired muscle and SAT biopsies from healthy human subjects. Both tissues expressed these transcripts, but IL-15Rα RNA levels were higher in SAT than in skeletal muscle. We also investigated tissue obtained from surgeries and found that SAT and VAT expressed equivalent amounts of IL-15 and IL-15Rα RNA, respectively. Furthermore, stromal vascular fraction cells expressed more IL-15 RNA than did adipocytes. To test if these findings related to circulating IL-15 protein and NK cell function, we tested 50 healthy adults aged > 70 years old. Plasma IL-15 levels significantly correlated with abdominal VAT mass in the entire cohort and in non-obese subjects. However, plasma IL-15 levels did not correlate with skeletal muscle cross-sectional area and correlated inversely with muscle strength. Plasma IL-15 did correlate with NK cell cytotoxic granule exocytosis and with CCL4 (MIP-1β) production in response to NKp46-crosslinking. Additionally, NK cell responses to K562 leukemia cells correlated inversely with muscle strength. With aging, immune function declines while infections, cancers, and deaths increase. We propose that VAT-derived IL-15 and IL-15Rα is a compensatory NK cell support mechanism in elderly humans.

Physical impairment in patients with idiopathic inflammatory myopathies is associated with the American College of Rheumatology functional status measure

The goals of this study were to assess the predictive value of chart-abstracted American College of Rheumatology functional status (ACR-FS) with patient-reported ACR-FS and to relate it with measures of muscle function in a single-institution cohort of patients with idiopathic inflammatory myopathies (IIMs). Demographic and clinical data of 102 patients with IIMs regularly followed in the Rheumatology and Neurology Clinics at the University of Kentucky Medical Center between 2006 and 2012 were obtained through retrospective chart review. Clinical and functional status evaluation, muscle performance testing, and body composition measures were performed on a subset of 21 patients. ACR-FS was obtained by both chart abstraction and direct patient report. Spearman’s correlations were used to examine the relationship of ACR-FS derived from chart abstraction with direct patient report, as well as the relationship of measures of physical function and body composition with ACR-FS. ACR-FS derived from chart abstraction was significantly correlated with ACR-FS derived from direct patient report (ρ = 0.78, p < 0.001). ACR-FS derived from chart abstraction was also significantly correlated with patient-reported physical function (ρ = −0.71, p < 0.001) and physical activity (ρ = −0.58, p < 0.05), manual muscle testing (ρ = −0.66, p < 0.01), and skeletal muscle endurance as measured by the functional index-2 test (shoulder flexion ρ = −0.62, p < 0.01; hip flexion ρ = −0.65, p < 0.0; heel lift ρ = −0.67, p < 0.01; and toe lift ρ = −0.68, p < 0.01). The ACR-FS is a simple measure of disability that can be used in chart abstraction studies involving IIM patients. We have demonstrated that ACR-FS correlates well with muscle performance tests of strength and endurance.

Tutorial for using SliceOmatic to calculate thigh area and composition from computed tomography images from older adults

Objective Area of muscle, fat, and bone is often measured in thigh CT scans when tissue composition is a key outcome. SliceOmatic software is commonly referenced for such analysis but published methods may be insufficient for new users. Thus, a quick start guide to calculating thigh composition using SliceOmatic has been developed. Methods CT images of the thigh were collected from older (69 ± 4 yrs, N = 24) adults before and after 12-weeks of resistance training. SliceOmatic was used to segment images into seven density regions encompassing fat, muscle, and bone from -190 to +2000 Hounsfield Units [HU]. The relative contributions to thigh area and the effects of tissue density overlap for skin and marrow with muscle and fat were determined. Results The largest contributors to the thigh were normal fat (-190 to -30 HU, 29.1 ± 7.4%) and muscle (35 to 100 HU, 48.9 ± 8.2%) while the smallest were high density (101 to 150 HU, 0.79 ± 0.50%) and very high density muscle (151 to 200 HU, 0.07 ± 0.02%). Training significantly (P<0.05) increased area for muscle in the very low (-29 to -1 HU, 5.5 ± 7.9%), low (0 to 34 HU, 9.6 ± 16.8%), normal (35 to 100 HU, 4.2 ± 7.9%), and high (100 to 150 HU, 70.9 ± 80.6%) density ranges for muscle. Normal fat, very high density muscle and bone did not change (P>0.05). Contributions to area were altered by ~1% or less and the results of training were not affected by accounting for skin and marrow. Conclusions When using SliceOmatic to calculate thigh composition, accounting for skin and marrow may not be necessary. We recommend defining muscle as -29 to +200 HU but that smaller ranges (e.g. low density muscle, 0 to 34 HU) can easily be examined for relationships with the health condition and intervention of interest. Trial registration Clinicaltrials.gov NCT02261961

THU0450 Relationship between the American College of Rheumatology (ACR) Classification Criteria of Functional Status and Clinical Predictors of Disability in Inflammatory Myopathies (IIM)

Background Many patients with IIMs exibit chronic muscle weakness and functional disability despite treatment. In polymyositis/ dermatomyositis (PM/DM), male sex, higher prednisone dosage and older age have been associated with muscle weakness and functional disability.[1,2] Sporadic inclusion body myositis (sIBM) itself is associated with major end-stage disability.[3] The ACR functional status (ACRFS) criteria have been used as a core measure of the consequences of impairment in IIM.[4] However, its association with known or suspected risk factors of disability warrants further investigation. Objectives To determine predictors of current/ worst ever ACRFS with known or suspected risk factors of disability and muscle weakness in patients with IIM. Methods Data were obtained from chart reviews of IIM and overlap myositis (OM) cases seen in the Rheumatology and Neurology Clinics at the University of Kentucky from May/06 until July/12. Current and worst ever ACRFS, demographic and clinical characteristics were abstracted from medical records. One-way ANOVA and Fisher’s exact/ Chi-square tests were used to compare groups on continuous/ categorical variables, respectively. Ordinal logistic regression was applied to estimate the effects of IIM type, age, sex and disease duration from diagnosis on current and worst ever ACRFS. Results 90 patients with IIM and OM were included: 38 PM, 29 DM, 12 IBM and 11 OM. When patient ages were divided into tertiles, sIBM patients were significantly older (p= 0.03). Females predominated in the PM, DM and OM groups. In sIBM, females were slightly outnumbered. Mean duration of disease from diagnosis was highest in sIBM (73 mo) compared to PM (39 mo), DM (18 mo) and OM (35 mo) (p=0.01). sIBM was more likely to be associated with presence of some degree of disability at the last time of assessment (91%), compared to all other groups combined (73%) (p=0.001). In the multivariable analysis, poorer current ACRFS and worst ever ACRFS were independently associated with higher age, and higher age and longer disease duration, respectively, controlling for all other variables. Conclusions The demographic and clinical characteristics of our cohort are consistent with previous reports. As expected, sIBM was associated with increased odds of disability. In the multivariate analysis, higher age and disease duration were identified as independent risk factors for disability. References Bronner IM, Van Der Meulen MF, De Visser M et al. Long-term outcome in polymyositis and dermatomyositis. Annals of the rheumatic diseases 65(11), 1456-1461 (2006). Clarke AE, Bloch DA, Medsger TA, Jr., Oddis CV. A longitudinal study of functional disability in a national cohort of patients with polymyositis/dermatomyositis. Arthritis and rheumatism 38(9), 1218-1224 (1995). Cox FM, Titulaer MJ, Sont JK, Wintzen AR, Verschuuren JJ, Badrising UA. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain : a journal of neurology 134(Pt 11), 3167-3175 (2011). Stucki G, Stoll T, Bruhlmann P, Michel BA. Construct validation of the ACR 1991 revised criteria for global functional status in rheumatoid arthritis. Clinical and experimental rheumatology 13(3), 349-352 (1995). Acknowledgements This study was supported by the Arthritis Foundation, the Center for Clinical and Translational Science (CCTS) at the University of Kentucky, the University of Kentucky College of Medicine Clinical Scholars Program and Research Data Capture (REDCap). Disclosure of Interest None Declared

THU0449 Utility of Ultrasound (US) in Assessing Skeletal Muscle Architecture in Idiopathic Inflammatory Myopathies (IIM)

Background IIM are systemic autoimmune diseases characterized by chronic inflammation in skeletal muscle leading to proximal muscle weakness. In rheumatoid arthritis, muscle weakness has been linked to specific changes in muscle architecture that are measureable using ultrasound (US).1 However, data regarding the contribution of muscle architecture to muscle weakness in IIM is lacking. US is a non-invasive, relatively inexpensive and validated method of assessing skeletal muscle architectural parameters [i.e. anatomic cross sectional area (ACSA), fascicle length (Lf), pennation angle (θ) and muscle thickness].2,3 US determination of Lf and θ allows calculation of the physiological cross sectional area of muscle, which is a better predictor of intrinsic muscle force compared to ACSA or volume.4 Objectives To test the utility of US in determining skeletal muscle architecture in patients with IIM. To investigate associations between rectus femoris muscle ACSA (RFACSA), muscle peak torque generation, and other clinical outcomes in patients with IIM. Methods Clinical data were obtained from chart reviews of IIM cases seen in the Rheumatology clinic at the University of Kentucky from May/2006 until Jan/2013. Participant body composition (DXA), mid-thigh bilateral RFACSA and right vastus lateralis fascicle length(VLLf) were measured with the knee extended and muscle relaxed. Right knee extensor and elbow flexor muscle-specific peak torques were measured using a Biodex dynamometer. Data were analyzed using descriptive statistics and Spearman rank correlation coefficient. Results 12 patients with IIM and overlap myositis (OM) were included: 2 polymyositis (PM), 4 dermatomyositis (DM), 5 sporadic inclusion body myositis (sIBM) and 1 OM. In 1 PM and 3 sIBM patients, muscle architecture was so disrupted that VLLf could not be measured. Right and left mean RFACSA were correlated (p=0.02). Mean RFACSA was inversely correlated with total body and thigh fat (p<0.05), and positively correlated with trunk lean mass and elbow flexor maximal voluntary isometric contraction (MVIC) (p<0.05). However, RFACSA did not correlate well with knee extensor MVIC. VLLf was measured in 3 DM patients (mean=7.92cm, SD=2.03) and 1 PM patient (6.79cm), which is in the described range.2 Conclusions RFACSA was associated with body composition. It is possible that in IIM, quadriceps muscle is weaker than predicted by RFACSA or lean body mass. In severe cases of IIM, in particular sIBM, substantial disruption of muscle architecture could be detected by US. References Matschke V, Murphy P, Lemmey AB, Maddison P, Thom JM. Skeletal muscle properties in rheumatoid arthritis patients. Medicine and science in sports and exercise 2010;42:2149-55. Chleboun GS, France AR, Crill MT, Braddock HK, Howell JN. In vivo measurement of fascicle length and pennation angle of the human biceps femoris muscle. Cells, tissues, organs 2001;169:401-9. Herbert RD, Gandevia SC. Changes in pennation with joint angle and muscle torque: in vivo measurements in human brachialis muscle. J Physiol 1995;484 ( Pt 2):523-32. Narici MV, Landoni L, Minetti AE. Assessment of human knee extensor muscles stress from in vivo physiological cross-sectional area and strength measurements. Eur J Appl Physiol Occup Physiol 1992;65:438-44. Acknowledgements This study was supported by the Arthritis Foundation, the Center for Clinical and Translational Science (CCTS) at the University of Kentucky, the University of Kentucky College of Medicine Clinical Scholars Program and Research Data Capture (REDCap). Disclosure of Interest None Declared