Operationalizing the Global Leadership Initiative in Sarcopenia: Muscle‐Specific Strength, Optimal Criteria and Clinical Relevance

ABSTRACT Background While the Global Leadership Initiative on Sarcopenia (GLIS) is promising to standardize sarcopenia diagnosis, its operational implementation remains largely undefined. This study aims to operationalize GLIS and evaluate its feasibility, diagnostic concordance and clinical relevance. Methods This three‐stage, multicenter study enrolled 12 116 participants for cut‐off development (mean age 58.7 years, 48.2% men) and 11 241 participants for outcome analysis (mean age 58.4 years, 49.4% men) from a national survey in China. Another 504 patients with chronic kidney disease were included for validation. We proposed the lower limb skeletal muscle mass to five‐time chair stand test ratio (LFR) to assess muscle‐specific strength (MSS). The GLIS conceptual framework was instantiated into six diagnostic criteria combinations using handgrip strength (HGS), appendicular skeletal muscle mass index (ASMI, estimated using a validated formula) and MSS: (1) all three criteria being low (HAM); (2) low HGS plus low ASMI (HA); (3) low MSS (M); (4) low HGS plus low ASMI, or low MSS (HA/M); (5) low HGS or low MSS (H/M); and (6) low ASMI or low MSS (A/M). Intercriteria concordance of these definitions, relevance with functional outcomes and their concordance with the Asian Working Group for Sarcopenia 2019 (AWGS) criteria were evaluated. Results Low MSS cut‐offs were established as < 0.74 for men and < 0.47 for women. Sarcopenia prevalence varied significantly across different definitions: 1055 (8.7%, AWGS), 405 (3.3%, HAM), 619 (5.1%, HA), 2409 (19.9%, M), 2623 (21.6%, HA/M), 3184 (26.3%, H/M) and 3868 (31.9%, A/M). The HA method showed the highest concordance with the AWGS (accuracy = 0.964, κ = 0.722, sensitivity = 1.000, specificity = 0.962). The H/M method demonstrated the strongest correlation with functional outcomes and optimal diagnostic performance (AUCs range from 0.566 to 0.729), with superior discrimination for impaired activities of daily living (ADL), other functional measures and global functional scores (p < 0.05). All methods independently predicted poor functional outcomes. External validation in CKD showed that the H/M method was either superior or comparable to other methods in identifying disabilities (e.g., predicting functional measures, AUC = 0.627, 95% CI = 0.582–0.672). Conclusions This study establishes an operational framework for GLIS using nationally representative data from China and validates its effectiveness in a clinical setting. LFR proves to be a feasible method for assessing MSS. The H/M method effectively captures functional impairment, which may serve as a useful approach for diagnosing sarcopenia. These findings provide actionable benchmarks for sarcopenia research and clinical practice, potentially informing more refined prevention and intervention strategies.