Neuromuscular biomarkers are associated with sarcopenia and physical performance in chronic pancreatitis: An integrative biomarker profiling study.

BACKGROUND

Chronic pancreatitis (CP) is associated with sarcopenia and functional decline, yet the underlying mechanisms remain underexplored. Neuromuscular junction (NMJ) degradation and neurotrophic imbalance may play key roles, but relevant studies remain scarce.

METHODS

We recruited 74 healthy controls, 65 patients with early CP, and 57 patients with advanced CP for evaluation of sarcopenia, including handgrip strength (HGS), muscle mass, and gait speed. Physical performance was measured using the Short Physical Performance Battery (SPPB). Plasma C-terminal agrin fragment-22 (CAF22; a marker of NMJ degradation), brain-derived neurotrophic factor (BDNF), and markers of inflammation, oxidative stress, and nutritional status were measured.

RESULTS

Sarcopenia prevalence and functional impairment increased significantly with CP severity. Plasma CAF22 showed a stepwise increase from controls to early and advanced CP, with increases of 10.2% and 24.3%, respectively. BDNF declined by 12.4% in advanced CP, while the total protein and albumin were lowest in advanced CP. CAF22 displayed robust associations with HGS, gait speed, and SPPB across all groups, with the largest effect sizes in advanced CP. BDNF exhibited positive associations with muscle function, while inflammatory, oxidative, and nutritional biomarkers exhibited weaker and stage-dependent relationships. These associations appeared to strengthen with worsening CP, suggesting that neuromuscular, inflammatory, and metabolic stressors may become more closely linked to functional decline in advanced disease.

CONCLUSION

CP is associated with progressive sarcopenia along with NMJ degeneration, neurotrophic imbalance, inflammation, oxidative stress, and nutritional decline. These findings highlight the potential value of CAF22 and BDNF as biomarkers of functional impairment.