Dataset Information

Estimation of skeletal muscle mass in 4-year-old children using the D₃-creatine dilution method.

ABSTRACT:

Background

Given 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.

Methods

Following 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.

Results

SMM 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).

Conclusions

The 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.

Impact

The 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.

SUBMITTER: Sidiqi A

PROVIDER: S-EPMC10444613 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Estimation of skeletal muscle mass in 4-year-old children using the D<sub>3</sub>-creatine dilution method.

Sidiqi Aysha A Fariha Farzana F Shanta Shaila S SS Dasiewicz Alison A Mahmud Abdullah Al AA Moore Daniel R DR Shankaran Mahalakshmi M Hellerstein Marc K MK Evans William J WJ Gernand Alison D AD Islam M Munirul MM Abrams Steven A SA Harrington Jennifer J Nyangau Edna E Roth Daniel E DE O'Callaghan Karen M KM

Pediatric research 20230410 3

<h4>Background</h4>Given limited experience in applying the creatine-(methyl-D<sub>3</sub>) (D<sub>3</sub>Cr) 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.<h4>Methods</h4>Following D<sub>3</sub>Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-d ...[more]

PMID: 37037953

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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:A noninvasive method to estimate muscle mass based on creatine ( methyl-d3) (D3-creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58-76 yr old) fasted overnight and then received an oral 30-mg dose of D3-creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3-4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography-tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D3-creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r?=?0.88, P < 0.0001), with less bias [difference from MRI?= -3.00?±?2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5?±?3.7 kg). However, intraindividual variability was high with the D3-creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D3-creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d3) (D3-creatine) and D3-creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D3-creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D3-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.

Project description:ObjectivesIt 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.DesignLongitudinal cohort study of participants in the Osteoporotic Fractures in Men (MrOS) study.Setting and participantsMuscle 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.MethodsClassification 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.ResultsWalking 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 implicationsThis 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.

Dataset Information

Estimation of skeletal muscle mass in 4-year-old children using the D₃-creatine dilution method.

Background

Methods

Results

Conclusions

Impact

Publications

Estimation of skeletal muscle mass in 4-year-old children using the D<sub>3</sub>-creatine dilution method.

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Dataset Information

Estimation of skeletal muscle mass in 4-year-old children using the D3-creatine dilution method.

Background

Methods

Results

Conclusions

Impact

Publications

Estimation of skeletal muscle mass in 4-year-old children using the D<sub>3</sub>-creatine dilution method.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Estimation of skeletal muscle mass in 4-year-old children using the D₃-creatine dilution method.