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

Abstract

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.

Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: A prospective study

“…However, the absence of objective mobility measures such as gait speed in the UK Biobank dataset led us to rely on self‐reported walking pace as a proxy indicator of mobility. 32 Nevertheless, it is important to acknowledge that the absence of such objective mobility measures may impact the accuracy and quantification of frailty assessments.…”

“… 30 The frailty phenotype encompasses five traits: weight loss, exhaustion, low physical activity, slow walking speed and low grip strength. 31 To adapt the data for use in the UK Biobank, we referred to previous reports and made slight adjustments to the criteria, 32 as outlined in Table S1 . Frailty status was evaluated based on the sum of scores for all five frailty items, with a higher total score indicating a higher frailty level.…”

“…Participants were categorized as frail (≥3 items met), pre‐frail (1–2 items met) or non‐frail (0 items met) accordingly. 32 …”

Association between frailty and gestational diabetes mellitus: a bidirectional and multivariable Mendelian randomization study

“…Frailty is characterized by decreased functioning of multiple physiological systems, which increases the risk of adverse health outcomes and can occur at all ages ( 29 , 44 ). Previous study on frailty and diabetes based on two prospective cohorts suggested that frailty was the predisposing factor for diabetes and increases its risk of death ( 11 , 18 ). At present, there is a lack of studies on frailty and GDM.…”

Mediating effects of depression on sleep disturbance and frailty in older adult type 2 diabetes patients in the community

“…Older adult T2DM patients with depression have significantly elevated levels of C-reactive protein, interleukin-6 and tumor cytokines, which also contribute to frailty ( 56 , 57 ). Meanwhile, older adult T2DM patients with depression are significantly less sociable and active and are more likely to have a sedentary lifestyle ( 58 ), which further contributes to muscle wasting. And muscle wasting and reduced muscle strength are important markers of frailty ( 59 ).…”