Muscle Metabolism Discovery Performance Unit, GlaxoSmithKline, Research Triangle Park, North Carolina.
Pennington Biomedical Research Center , Baton Rouge, Louisiana.
J Appl Physiol (1985). 2018 Jan 1;124(1):1-9. doi: 10.1152/japplphysiol.00455.2016. Epub 2017 Aug 31.
A noninvasive method to estimate muscle mass based on creatine ( methyl-d) (D-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 D-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 D-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). D-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 D-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 D-creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d) (D-creatine) and D-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 D-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 D-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.
一种基于肌酸（甲基-d）（D-肌酸）稀释的非侵入性方法，使用禁食晨尿来评估肌肉量，其在 3 至 4 个月的期间内的准确性和可变性。健康的老年人（67 至 80 岁）受试者（n=14）因衰老而出现肌肉减少症，以及 4 名患有慢性疾病（58 至 76 岁）的患者在禁食过夜后，于上午 8 点（第 1 天）口服 30mg D-肌酸。在继续禁食 4 小时期间收集尿液，然后在第 5 天通过连续 4 至 8 小时的间隔收集尿液。在 13 名健康受试者和 1 名充血性心力衰竭患者中，3-4 个月后重复评估。使用液相色谱-串联质谱法测量氘代和未标记的肌酸和肌酸酐。从尿液中 D-肌酸的富集来计算全身肌酸池大小和肌肉量。肌肉量也通过全身 MRI 和 24 小时尿肌酸酐测量，通过双能 X 射线吸收法（DXA）测量瘦体重（LBM）。第 5 天的 D-肌酸尿浓缩物提供的肌肉量估计值与所有受试者的 MRI 相关（r=0.88，P<0.0001），与 DXA 对总 LBM 的评估相比，偏差更小[与 MRI 的差异=-3.00±2.75（SD）kg]，后者高估了肌肉量（+22.5±3.7kg）。然而，D-肌酸稀释法的个体内变异性较高，估计肌肉量的个体内标准差为 2.5kg 与 MRI（0.5kg）和 DXA（0.8kg）相比。这项研究支持进一步临床验证 D-肌酸法来估计肌肉量。本研究支持进一步临床验证 D-肌酸法来估计肌肉量。本研究支持进一步临床验证 D-肌酸法来估计肌肉量。新观点和重要性测量禁食晨尿尿样中的肌酸（甲基-d）（D-肌酸）和 D-肌酸的排泄可能是一种简单、成本较低的替代 MRI 或双能 X 射线吸收法（DXA）来计算全身肌肉量的方法。D-肌酸富集法提供的肌肉量估计值与 MRI 相关性良好，且偏差小于 DXA。然而，D-肌酸法的个体内变异性较高。可能需要进一步研究来改进用于估计肌肉量的尿液样本方法。
