Associations Between Frailty and the Increased Risk of Adverse Outcomes Among 38,950 UK Biobank Participants With Prediabetes: Prospective Cohort Study

BACKGROUND: Compared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. OBJECTIVE: We aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. METHODS: We evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. RESULTS: At baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <.001). For instance, compared with their nonfrail counterparts, frail participants with prediabetes had a significantly higher risk (P<.001) of T2DM (hazard ratio [HR]=1.73, 95% CI 1.55-1.92), diabetes-related microvascular disease (HR=1.89, 95% CI 1.64-2.18), CVD (HR=1.66, 95% CI 1.44-1.91), CKD (HR=1.76, 95% CI 1.45-2.13), eye disease (HR=1.31, 95% CI 1.14-1.51), dementia (HR=2.03, 95% CI 1.33-3.09), depression (HR=3.01, 95% CI 2.47-3.67), and all-cause mortality (HR=1.81, 95% CI 1.51-2.16) 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%. Robust results were generally observed in sensitivity analyses. CONCLUSIONS: In UK Biobank participants with prediabetes, both prefrailty 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 routine care for middle-aged adults with prediabetes, to improve the allocation of health care resources and reduce diabetes-related burden.