D3-creatine dilution for the noninvasive measurement of skeletal muscle mass in premature infants

Evans, William J.; Scottoline, Brian; Imam, Faryal; Hellerstein, Marc K.; Garton, Kelly; Czerwieniec, Gregg; Nyangau, Edna; Shankaran, Mahalakshmi

doi:10.1038/s41390-020-01122-w

Cited by 17 publications

(21 citation statements)

References 26 publications

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“…In a previously published A c c e p t e d M a n u s c r i p t study 27 , repeat measurements were made on urine samples from participants with wide range of ages revealing a coefficient of variation of 3.6%. Moreover, very small longitudinal changes in D3Cr muscle mass can be detected in infants 28 , further demonstrating the precision of the technique.…”

Section: Cr Dilution Methods To Estimate Muscle Massmentioning

confidence: 76%

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men

Orwoll

Blackwell

Cummings

et al. 2021

The Journals of Gerontology: Series A

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Background Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat vs. muscle fat to adverse outcomes have been unclear. Methods In a large cohort of older men (N= 1017), we measured muscle mass (D3 creatine dilution), muscle density (high resolution peripheral computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years. Results In combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% CI: 0.74, 0.70), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively. Conclusions Muscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

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Section: Cr Dilution Methods To Estimate Muscle Massmentioning

confidence: 76%

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men

Orwoll

Blackwell

Cummings

et al. 2021

The Journals of Gerontology: Series A

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“…In neonates, however, muscle increases in mass at a rate averaging about 17% per day and this growth is accompanied by an increase in the creatine pool size. 35 This is likely why the tracer enrichment (D 3 ‐creatinine to total creatinine ratio in urine) does not reach a plateau in neonates. The plateau method is therefore not appropriate for estimating enrichment, as equilibration of the tracer cannot be identified by a flat (unchanging) period in the enrichment vs. time graph.…”

Section: Creatine‐( Methyl ‐D 3 ...mentioning

confidence: 99%

D₃‐creatine dilution for skeletal muscle mass measurement: historical development and current status

McCarthy

Schoeller

Brown

et al. 2022

J cachexia sarcopenia muscle

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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-d 3 )) 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.

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“…The enrichment of urine D 3 ‐creatinine thereby reveals the enrichment of intramyocellular D 3 Cr and provides a noninvasive measurement of total‐body muscle mass. The method has been validated in rodents, adult humans, 5 and premature infants cared for in a neonatal intensive care unit (NICU) 6 . In these neonates, substantial increases in muscle mass (measured every 2 weeks during care in the NICU) were observed.…”

Section: Figurementioning

confidence: 99%

“…The method has been validated in rodents, adult humans, 5 and premature infants cared for in a neonatal intensive care unit (NICU). 6 In these neonates, substantial increases in muscle mass (measured every 2 weeks during care in the NICU) were observed. Importantly, the method was able to determine changes of 100-200 g. The method only requires a single "spot" urine sample, and there is no need for a skilled technician to administer a dose or collect a urine sample.…”

mentioning

confidence: 95%

Lean body mass should not be used as a surrogate measurement of muscle mass in malnourished men and women: Comment on Compher et al.

Evans

2022

J Parenter Enteral Nutr

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D3-creatine dilution for the noninvasive measurement of skeletal muscle mass in premature infants

Cited by 17 publications

References 26 publications

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men

D₃‐creatine dilution for skeletal muscle mass measurement: historical development and current status

Lean body mass should not be used as a surrogate measurement of muscle mass in malnourished men and women: Comment on Compher et al.

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D3-creatine dilution for the noninvasive measurement of skeletal muscle mass in premature infants

Cited by 17 publications

References 26 publications

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men

D3‐creatine dilution for skeletal muscle mass measurement: historical development and current status

Lean body mass should not be used as a surrogate measurement of muscle mass in malnourished men and women: Comment on Compher et al.

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D₃‐creatine dilution for skeletal muscle mass measurement: historical development and current status