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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by a grant from the National Natural Science Foundation of China (82171584), the Fundamental Research Funds for the Central Universities, Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province (2020E10004), and Zhejiang University Global Partnership Fund (188170-11103). Dr. Gill is supported by the Claude D. Pepper Older Americans Independence Center at Yale School of Medicine from the National Institute on Aging (P30AG021342); and the National Center for Advancing Translational Sciences (UL1TR001863). The funders had no role in the study design; data collection, analysis, or interpretation; in the writing of the report; or in the decision to submit the article for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: www.ukbiobank.ac.uk/register-apply. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data from UK Biobank are available on application at www.ukbiobank.ac.uk/register-apply.