Department Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA.
Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
J Physiol. 2024 Oct;602(19):4929-4939. doi: 10.1113/JP287069. Epub 2024 Aug 31.
Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the Dcreatine (DCr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of DCr dissolved in water was ingested by 92 patients with DMD (ages 4-25 years) followed later with a fasting urine sample. Enrichment of Dcreatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The DCr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive Dcreatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.
杜氏肌营养不良症（DMD）导致功能性骨骼肌质量（MM）进行性丧失，并被纤维脂肪组织取代。以前无法对 DMD 患者的 MM 进行准确评估。我们的目的是使用 Dcreatine（DCr）稀释法测量 MM，并确定其与 DMD 患者在广泛年龄范围内的力量和功能能力的关系。招募受试者参加为期 12 个月的纵向观察研究。在这里，我们报告基线数据。92 名 DMD 患者（年龄 4-25 岁）口服 20mg 的 DCr 溶解在水中，随后采集空腹尿液样本。通过液相色谱-质谱分析确定 Dcreatinine 的富集度。对有活动能力的参与者进行了 North Star 活动评估（NSAA）总分的测定，对所有参与者进行了上肢表现（PUL 2.0）总分和握力的测定。我们观察到体重与 MM/体重（%MM）呈显著的年龄相关增加。MM 和 %MM 与 PUL 评分相关（r=0.517，P<0.0001 和 r=0.764，P<0.0001）。MM 和 %MM 随年龄的下降与活动能力状态密切相关。我们观察到，有活动能力和无活动能力的受试者之间的 %MM 几乎没有重叠，这表明与丧失活动能力相关的阈值为 18-22%。随着年龄的增长，MM 显著减少，与具有临床意义的功能状态高度相关。DCr 稀释法可能为 DMD 或其他神经肌肉疾病患者的疾病进展和治疗效果提供生物标志物。关键点：非侵入性的 Dcreatine 稀释法为 DMD 患者在广泛的年龄范围内提供了关于全身功能性肌肉质量（MM）的新数据，并揭示了年龄较大的非活动能力患者中功能 MM 极低。有活动能力和无活动能力的受试者之间的 %MM 差异表明，在 18-22% MM 之间存在丧失活动能力的阈值。数据表明，随着年龄的增长，功能性 MM 下降，保持较低的体重可能有助于保持活动能力。
