Metabolic Syndrome as a Determinant of Bidirectional Transitions Between Frailty States: Evidence From the Whitehall...

Understanding interactions between geriatric syndromes is central for promoting healthy aging. Frailty is among the most relevant, as it predicts disability, falls, hospitalization and mortality. In addition, emerging evidence also indicates that metabolic factors play a key role in the frailty development. Among them, metabolic syndrome (MetS) has been examined because of shared metabolic, inflammatory and endocrine mechanisms. Previous studies reported that MetS and its components increase the risk of pre-frailty and frailty. However, the role of MetS in the dynamics of frailty trajectories, namely, transitions between frailty states, remains poorly understood. Using data from the Whitehall II cohort, we examined the influence of MetS and its components on bidirectional transitions between the frailty states.

Data from Phases 9, 11 and 12 of the Whitehall II cohort (n = 10 308) were analysed. MetS and its five components were defined at baseline according to the consensus definition. Frailty states were classified using Fried's phenotype: robust (0 criteria), pre-frailty 1 (PF-1; 1 criterion), pre-frailty 2 (PF-2; 2 criteria) and frailty (≥ 3 criteria). A multi-state Markov model with death as an absorbing competing state was used to estimate transition intensities and probabilities. Transition-specific hazard ratio (HR) for MetS and its components were adjusted for sociodemographic, lifestyle and health-related factors.

A total of 4750 participants (mean age: 64.6 years; 73.9% men) were followed for an average of 6.9 years. At baseline, 58.8% were robust, 29.4% were PF-1, 9.2% were PF-2, and 2.5% were frail; 36.9% had MetS. Recovery transitions were more frequent than deteriorations: Among PF-1 individuals, recovery to robustness occurred at an intensity of 0.20 (95% CI: 0.18-0.22) versus 0.15 (0.14-0.17) for progression to PF-2. In PF-2, recovery to PF-1 was 0.30 (0.26-0.35), versus 0.15 (0.12-0.18) for progression to frailty. Overall, MetS was not significantly associated with transitions. However, abdominal obesity increased the hazard of transitioning from robustness to PF-1 by 27% (HR = 1.27; 1.09-1.48; p = 0.001) and reduced recovery from PF-2 to PF-1 by 28% (HR = 0.72; 0.52-0.99; p = 0.04) and from frailty to PF-2 by 50% (HR = 0.50; 0.29-0.87; p = 0.014). Hyperglycemia reduced recovery from PF-1 to robustness by 28% (HR: 0.72; 0.59-0.88; p < 0.001). Other components, including hypertension, high blood levels of triglycerides and low blood levels of HDL-cholesterol, showed no significant associations.

MetS overall was not significantly associated with frailty transitions. Nevertheless, abdominal obesity and hyperglycemia were linked to impaired recovery and accelerated progression toward frailty. Early intervention targeting these metabolic disturbances may support healthier aging trajectories.