Dataset Information

Walking Speed and Muscle Mass Estimated by the D₃-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.

ABSTRACT:

Objectives

It is unknown whether muscle mass measured by the D₃-creatine dilution method is a superior predictor of incident mobility disability than traditional components of sarcopenia definitions (including grip strength, walking speed, appendicular lean mass). The objective of this study was to determine the relative importance of strength; physical performance; and lean, fat, and muscle mass in predicting incident mobility disability in older men.

Design

Longitudinal cohort study of participants in the Osteoporotic Fractures in Men (MrOS) study.

Setting and participants

Muscle mass was assessed by D₃-creatine dilution in 1098 men (aged 83.7 ± 3.7 years). Participants also completed anthropomorphic measures, 6-m walking speed (m/s), grip strength (kg), chair stands (seconds), and dual x-ray absorptiometry appendicular lean mass (ALM), and total body fat percentage. Men self-reported incident mobility disability defined by the development of an inability to complete at least one of walking 2-3 blocks, climbing 10 steps, or carrying 10 lb over 2.2 ± 0.3 years.

Methods

Classification and regression tree analysis was conducted to determine relative variable importance and algorithm cutpoints for predicting incident mobility disability. Given the proximity of walking speed with the primary outcome (mobility disability), analyses were conducted with and without walking speed.

Results

Walking speed followed by D₃Cr muscle mass/weight were the most important variables (variable importance: 53% and 12%, respectively) in the prediction of self-reported incident mobility disability. D₃Cr muscle mass was the most important variable in predicting incident mobility disability when walking speed was excluded, followed by chair stands (variable importance: 35% and 33%, respectively). Body fat percentage, ALM, and grip strength were not selected as nodes in either analysis and had low or negligible variable importance.

Conclusions and implications

This study has provided valuable insights into the importance of different variables in predicting incident mobility disability in older men. Muscle mass by D₃Cr may be a key tool for predicting the risk of negative outcomes in older adults in the future, particularly in post-acute and long-term care settings.

SUBMITTER: Zanker J

PROVIDER: S-EPMC8057698 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Walking Speed and Muscle Mass Estimated by the D<sub>3</sub>-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.

Zanker Jesse J Patel Sheena S Blackwell Terri T Duchowny Kate K Brennan-Olsen Sharon S Cummings Steven R SR Evans William J WJ Orwoll Eric S ES Scott David D Vogrin Sara S Cauley Jane A JA Duque Gustavo G Cawthon Peggy M PM

Journal of the American Medical Directors Association 20200504 12

<h4>Objectives</h4>It is unknown whether muscle mass measured by the D<sub>3</sub>-creatine dilution method is a superior predictor of incident mobility disability than traditional components of sarcopenia definitions (including grip strength, walking speed, appendicular lean mass). The objective of this study was to determine the relative importance of strength; physical performance; and lean, fat, and muscle mass in predicting incident mobility disability in older men.<h4>Design</h4>Longitudin ...[more]

PMID: 32381425

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Project description:The French chemist Michel Eugène Chevreul discovered creatine in meat two centuries ago. Extensive biochemical and physiological studies of this organic molecule followed with confirmation that creatine is found within the cytoplasm and mitochondria of human skeletal muscles. Two groups of investigators exploited these relationships five decades ago by first estimating the creatine pool size in vivo with 14 C and 15 N labelled isotopes. Skeletal muscle mass (kg) was then calculated by dividing the creatine pool size (g) by muscle creatine concentration (g/kg) measured on a single muscle biopsy or estimated from the literature. This approach for quantifying skeletal muscle mass is generating renewed interest with the recent introduction of a practical stable isotope (creatine-(methyl-d3 )) dilution method for estimating the creatine pool size across the full human lifespan. The need for a muscle biopsy has been eliminated by assuming a constant value for whole-body skeletal muscle creatine concentration of 4.3 g/kg wet weight. The current single compartment model of estimating creatine pool size and skeletal muscle mass rests on four main assumptions: tracer absorption is complete; tracer is all retained; tracer is distributed solely in skeletal muscle; and skeletal muscle creatine concentration is known and constant. Three of these assumptions are false to varying degrees. Not all tracer is retained with urinary isotope losses ranging from 0% to 9%; an empirical equation requiring further validation is used to correct for spillage. Not all tracer is distributed in skeletal muscle with non-muscle creatine sources ranging from 2% to 10% with a definitive value lacking. Lastly, skeletal muscle creatine concentration is not constant and varies between muscles (e.g. 3.89-4.62 g/kg), with diets (e.g. vegetarian and omnivore), across age groups (e.g. middle-age, ~4.5 g/kg; old-age, 4.0 g/kg), activity levels (e.g. athletes, ~5 g/kg) and in disease states (e.g. muscular dystrophies, <3 g/kg). Some of the variability in skeletal muscle creatine concentrations can be attributed to heterogeneity in the proportions of wet skeletal muscle as myofibres, connective tissues, and fat. These observations raise serious concerns regarding the accuracy of the deuterated-creatine dilution method for estimating total body skeletal muscle mass as now defined by cadaver analyses of whole wet tissues and in vivo approaches such as magnetic resonance imaging. A new framework is needed in thinking about how this potentially valuable method for measuring the creatine pool size in vivo can be used in the future to study skeletal muscle biology in health and disease.

Project description:BackgroundThe Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements.DesignCross-sectional data analyses of pooled data.SettingUniversity-based research assessment centers.ParticipantsCommunity-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed.MeasurementsThirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously).ResultsCART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m2 or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m2 . Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers.ConclusionGR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements. J Am Geriatr Soc 68:1419-1428, 2020.

Project description:BackgroundGiven limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh.MethodsFollowing D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer.ResultsSMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91).ConclusionsThe D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach.ImpactThe D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Project description:BackgroundSarcopenia-related parameters may have differential impacts on health-related outcomes in older adults. We examined dose-response relationships of body composition, muscle strength, and physical performance with incident disability and mortality.MethodsThis prospective study included 1765 Japanese residents (862 men; 903 women) aged ≥65 years who participated in health check-ups. Outcomes were incident disability and all-cause mortality. Fat mass index (FMI) and skeletal muscle mass index (SMI), determined using segmental multi-frequency bioelectrical impedance analysis, handgrip strength (HGS), and usual gait speed (UGS) were measured. We determined multivariate-adjusted hazard ratios (HRs) for disability and mortality relative to sex-specific reference values (FMI: medians; SMI: 7.0 kg/m2 for men and 5.7 kg/m2 for women; HGS: 28 kg for men and 18 kg for women; or UGS: 1.0 m/s for both sexes). Association shapes were examined using restricted cubic splines or fractional polynomial functions.ResultsThe median follow-up was 5.3 years; 107 (12.7%) men and 123 (14.2%) women developed disability, and 101 (11.7%) men and 56 (6.2%) women died. FMI did not impact any outcome in men and disability in women, while an FMI ≤ 7.3 kg/m2 (median) was significantly associated with higher mortality risk in women, compared with median FMI. SMI did not impact disability in either sex and mortality in women, but showed a significant inverse dose-response relationship with mortality risk in men [HRs (95% confidence intervals) of minimum and maximum values compared with the reference value: 2.18 (1.07-4.46) and 0.43 (0.20-0.93), respectively], independent of HGS and UGS. HGS and UGS showed a significant inverse dose-response relationship with disability in both sexes [HGS: 1.71 (1.00-2.91) and 0.31 (0.09-0.99), respectively, in men, 2.42 (1.18-4.96) and 0.41 (0.20-0.85), respectively, in women; UGS: 2.14 (1.23-3.74) and 0.23 (0.08-0.67), respectively, in men, 3.26 (2.07-5.14) and 0.11 (0.05-0.26), respectively, in women] and mortality in women [HGS: 6.84 (2.84-16.47) and 0.06 (0.02-0.21), respectively; UGS: 2.67 (1.14-6.27) and 0.30 (0.11-0.85), respectively], independent of body composition, but did not impact mortality in men.ConclusionsDisability risk was more dependent on muscle strength and physical performance in both sexes. Mortality risk in men was more dependent on muscle mass, and mortality risk in women was influenced by lower fat mass along with muscle strength and physical performance. Although improving muscle strength and physical performance should be the first target for health promotion, it is also necessary to pay attention to body composition to extend life expectancy in older adults.

Dataset Information

Walking Speed and Muscle Mass Estimated by the D₃-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.

Objectives

Design

Setting and participants

Methods

Results

Conclusions and implications

Publications

Walking Speed and Muscle Mass Estimated by the D<sub>3</sub>-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Walking Speed and Muscle Mass Estimated by the D3-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.

Objectives

Design

Setting and participants

Methods

Results

Conclusions and implications

Publications

Walking Speed and Muscle Mass Estimated by the D<sub>3</sub>-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Walking Speed and Muscle Mass Estimated by the D₃-Creatine Dilution Method Are Important Components of Sarcopenia Associated With Incident Mobility Disability in Older Men: A Classification and Regression Tree Analysis.