Diabetology & Metabolic Syndrome · Jun 23, 2026

Association of frailty and metabolism with multi-state model in fatty liver disease, diabetes mellitus and all-cause mortality

By Wang X, Jin C, Zhong Q et al.

OBJECTIVE: Frailty is a global public health issue, and metabolic syndrome (MetS) is also associated with a variety of adverse health outcomes. However, the relationship between the combined effects of these two factors and the occurrence and progression of long-term diseases remains unclear. METHODS: This is a population-based cohort study involving 165,555 participants from the UK Biobank. We combined frailty status scores with metabolic condition scores to assess the predictive value. Associations were assessed using multi-state model, corrected Cox models, restricted cubic spline, stratified analysis, Kaplan-Meier analysis. RESULTS: During the 12.7-year follow-up period, 3,585 individuals were newly diagnosed with metabolic-associated fatty liver disease (MAFLD), among whom 170 developed non-insulin-dependent diabetes mellitus (NIDDM) and 699 died from all causes. Compared with Group 1(neither frailty nor MetS), the HR and 95% confidence intervals for Group 4 (both frailty and MetS) was 2.92 (2.45-3.47) for MAFLD, 4.21 (2.23-7.96) for MAFLD→NIDDM, and 1.22 (0.75-2.02) for MAFLD→Death. The Kaplan-Meier analysis further confirmed these findings. Consistent findings regarding the frailty phenotype and MetS had also been observed in the progression of NIDDM. CONCLUSION: This study demonstrates a positive association between frailty phenotype and MetS in disease onset and progression, and their combined assessment enables a more effective early risk stratification.

doi.org/10.1186/s13098-026-02201-4Open accessPubMed 42337554Populations