Systemic Inflammation and its association with functional impairment and mortality in patients with disease-related malnutrition: findings from the AFEDIN cohort

Introduction The Global Leadership Initiative on Malnutrition (GLIM) framework incorporates inflammation as a key etiologic criterion for diagnosing disease-related malnutrition (DRM), yet the clinical implications of systemic inflammation, particularly as quantified by C-reactive protein (CRP), remain insufficiently characterized. Methods To evaluate whether CRP-based inflammation thresholds proposed by GLIM are associated with impaired nutritional status, diminished functional capacity, reduced quality of life, and increased short-term mortality in ambulatory patients with DRM. This prospective, multicenter cohort study (AFEDIN – Analysis of the Etiological Factors of Malnutrition: Inflammation and Intake) included 266 ambulatory patients with DRM and CRP > 3 mg/L. Participants underwent comprehensive nutritional assessment via anthropometry, bioelectrical impedance, and nutritional ultrasound, alongside functional testing (handgrip strength, Timed Up and Go, chair stand test), quality of life evaluation (EQ-5D-5L), and inflammatory profiling. Patients were stratified by CRP levels into mild (3–9.9 mg/L), moderate (10–49.9 mg/L), and severe (≥50 mg/L) inflammation groups. Results C-reactive protein levels were strongly associated with inflammatory and biochemical markers but not with direct measures of body composition. Higher CRP concentrations correlated with reduced performance on functional tests and increased difficulty with self-care. Mortality increased markedly across CRP strata (1.1%, 11.8%, and 17.7%, respectively; p < 0.001). Compared to patients with CRP levels of 3–9.9 mg/L, those with CRP ≥ 50 mg/L had a significantly higher risk of mortality (OR 20.14, 95% CI 2.47–164.1, p < 0.05), as did those with CRP 10–49.9 mg/L (OR 12.53, 95% CI 1.62–97.1, p < 0.05). Conclusion In ambulatory DRM patients, higher CRP levels predict functional impairment and mortality, highlighting the prognostic utility of CRP within the GLIM framework. Inflammation should be routinely quantified to enhance risk stratification and guide intervention.