(P18-14-26) Amino Acid Signatures Linked to Muscle Health and Clinical Outcomes in Adults With Cystic Fibrosis

Objectives: In adults with cystic fibrosis (awCF), impairments in skeletal muscle quantity, quality, and strength are associated with adverse clinical outcomes. Altered amino acid (AA) metabolism may contribute to these complications. We aimed to characterize associations between plasma AA profiles and skeletal muscle health in clinically stable awCF and examine relationships with clinical outcomes.

Methods: This cross-sectional study included 77 awCF and 35 healthy controls. Appendicular skeletal muscle index (ASMI) was determined with DEXA, muscle quality by phase angle (PhA) using bioimpedance, and muscle strength by handgrip (HGS). Clinical outcomes included physical function [1-min sit-to-stand test (STST)], lung function (FEV1%), and glucose tolerance [fasting and 2-h glucose from a 75-g OGTT, Matsuda insulin sensitivity index (ISI-M)]. A 19-plasma-AA panel was quantified using dual-column high-resolution liquid chromatography–mass spectrometry. Generalized linear models adjusted for disease status, age, and sex assessed associations between AAs and muscle indicators; awCF-only models additionally examined relationships with muscle indicators and clinical outcomes.

Results: Glutamate and proline levels were positively related to ASMI in controls but inversely in awCF. Tryptophan levels were inversely associated with ASMI, PhA, and HGS in controls but positively associated in awCF. Histidine showed a similar pattern for HGS. In awCF-only analyses, branched-chain and aromatic AAs were positively linked to PhA, HGS, and ASMI. Methionine and proline levels were positively related to STST and FPG, whereas glutamine and alanine levels were inversely related to 2h glucose and ISI-M. Glutamate uniquely linked PhA with lung function.

Conclusions: AAs are differentially associated with skeletal muscle indicators in awCF relative to healthy controls, suggesting disease-specific metabolic signatures. Lower tryptophan and higher glutamate levels in awCF may reflect disruptions in anabolic signaling, cellular energetics, and inflammatory pathways, potentially contributing to impaired muscle health and adverse clinical outcomes. These findings identify candidate AA signatures linking skeletal muscle status with clinical outcomes in awCF and warrant further mechanistic and translational investigation.

Funding Sources: NIH, CFF, and GCTSA