Association between metabolic dysregulation and frailty in four prospective cohorts

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.