Frailty increases the risk of adverse outcomes among 38,950 UK Biobank participants with prediabetes: A prospective cohort study

Background: We aimed to systematically evaluate the associations of frailty, a simple health indicator, with risks of multiple adverse outcomes in late life among adults with prediabetes. Methods: We evaluated 38,950 adults aged 40-64 years with prediabetes from the baseline survey of the UK Biobank. Frailty was assessed using the frailty phenotype (FP, 0-5), and participants were grouped into non-frail (FP =0), pre-frail (1[≤] FP [≤]2), and frail (FP [≥]3). Multiple health outcomes were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Results: At baseline, 49.1% and 5.9% of adults with prediabetes were identified as pre-frail and frail, respectively. Both pre-frailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <0.001). For instance, compared with their non-frail counterparts, frail participants with prediabetes had a significantly higher risk (P <0.001) of type 2 diabetes mellitus (T2DM) (hazard ratio [HR]: 1.73), diabetes-related microvascular disease (HR: 1.89), cardiovascular disease (HR: 1.66), chronic kidney disease (HR: 1.76), eye disease (HR: 1.31), dementia (HR: 2.03), depression (HR: 3.01), and all-cause mortality (HR: 1.81) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%. Conclusions: In UK adults with prediabetes, both pre-frailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into the routine care for middle-aged adults with prediabetes, to improve the allocation of healthcare resources and reduce diabetes-related burdens.