O063 - METABOLOMICS-BASED PHENOTYPING IDENTIFIES DISTINCT SARCOPENIA SUBTYPES WITH DIFFERENTIAL MORTALITY RISK: A PROSPECTIVE COHORT STUDY FROM UK BIOBANK

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O063

METABOLOMICS-BASED PHENOTYPING IDENTIFIES DISTINCT SARCOPENIA SUBTYPES WITH DIFFERENTIAL MORTALITY RISK: A PROSPECTIVE COHORT STUDY FROM UK BIOBANK

X. Liu1, Y. Zhao1, Y. Li1, W. Yang1, N. Chen1, T. Liang1, J. Cui1,*

1The First Hospital of Jilin University, Changchun, China

 

Rationale: Sarcopenia represents a heterogeneous condition with variable clinical outcomes. Whether metabolic phenotyping can identify clinically meaningful sarcopenia subtypes remains unknown.

Methods: We analyzed 1,811 participants with sarcopenia from the UK Biobank who had complete metabolomics and proteomics data. Sarcopenia was diagnosed using EWGSOP2 criteria. Unsupervised clustering based on metabolic profiles identified distinct phenotypes, visualized by Uniform Manifold Approximation and Projection (UMAP). Cox proportional hazards models assessed associations with all-cause and cause-specific mortality across three adjusted models.

Results: Three metabolically distinct sarcopenia clusters emerged: Cluster 0 (n=775), Cluster 1 (n=565), and Cluster 2 (n=471). Cluster 2 exhibited the highest mortality risk across all models (all-cause mortality HR 1.68, 95% CI 1.24-2.28, P=0.001; cancer mortality HR 1.71, 95% CI 1.02-2.86, P=0.042; circulatory mortality HR 2.10, 95% CI 1.09-4.05, P=0.027 in fully adjusted models). This high-risk phenotype was characterized by pronounced VLDL-triglyceride axis dysregulation, elevated diabetes prevalence (38.85% vs 4.25-20.13%), and higher BMI (33.87 kg/m²). Proteomic profiling revealed upregulation of FGF21 and GCG, with downregulation of GH1 and IGFBP1 in Cluster 2, enriched in neuroendocrine signaling and feeding behavior pathways. Mortality risk stratification remained consistent across demographic, lifestyle, and genetic subgroups (all P for interaction >0.05).

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Conclusion: Metabolomics-based phenotyping identifies three sarcopenia subtypes with distinct mortality trajectories. The high-risk Cluster 2 phenotype, characterized by VLDL-triglyceride dysregulation and neuroendocrine disruption, may benefit from targeted metabolic interventions. These findings support precision medicine approaches in sarcopenia management.

Disclosure of Interest: None declared