Abstract
OBJECTIVES: The relationship between metabolic dysregulation and frailty remains incompletely understood. This study examines the association between metabolic dysregulation and frailty in middle-aged and older adults. METHODS: Data from four cohorts (CHARLS, HRS, SHARE, MHAS) were analysed. Frailty was assessed using a 30-item deficit accumulation frailty index, treated as a continuous variable ranging from 0-100. Metabolic dysregulation was defined based on the presence of central obesity, high blood pressure, and/or hyperglycaemia, and was analysed both as a categorical count variable (0, 1, 2, or 3 dysregulations) and as specific combinations of individual metabolic components. Multivariable linear regression models were used to examine associations, adjusting for demographic, lifestyle, and clinical factors. RESULTS: Among 416,693 participants, 63.7% had at least one metabolic dysregulation. A dose-response pattern was observed: β-values for frailty were 4.31 (95% CI: 4.22-4.40) for one dysregulation, 8.36 (95% CI: 8.24-8.49) for two, and 12.92 (95% CI: 12.79-13.16) for three. Hyperglycemia had the strongest effect, especially when combined with high blood pressure, and remained significant after adjustment. CONCLUSION: Metabolic dysregulation synergistically accelerates frailty progression, underscoring the need for early intervention in metabolic disorders to prevent frailty.