虚弱状态与成人1型糖尿病死亡和血管并发症风险的关联研究

Frailty and risk of mortality and vascular complications in adults with type 1 diabetes

摘要

目的：探究成人1型糖尿病（type 1 diabetes，T1D）患者的虚弱状态与死亡及血管并发症发生风险的关联。方法：基于英国生物银行（UK Biobank，UKB）前瞻性队列，纳入基线确诊的T1D患者。采用躯体虚弱（physical frailty，PF）和虚弱指数（frailty index，FI）评估基线虚弱状态。主要结局包括全因死亡、T1D及其并发症相关死亡，以及新发大血管和微血管并发症。采用Cox比例风险回归模型评估虚弱状态与各结局的关联，计算风险比（hazard ratio，HR）及95%置信区间（confidence interval，CI），进行剂量-反应分析、分层分析及敏感性分析。结果：共纳入1 571例基线T1D患者用于死亡结局分析，中位随访13.4年；其中1 207例基线无血管并发症的患者纳入并发症分析。根据PF和FI评估，分别有12.7%和28.5%的参与者被归类为虚弱。多变量调整后，与非虚弱组相比，虚弱组全因死亡风险显著升高（PF：HR=2.76，95% CI：1.92~3.98；FI：HR=2.71，95% CI：1.71~4.31），T1D及其并发症相关死亡风险亦增加（PF：HR=4.02，95% CI：2.21~7.28；FI：HR=4.14，95% CI：1.73~9.89）。在基线无血管并发症的患者中，虚弱与新发大血管并发症（PF：HR=2.17，95% CI：1.46~3.22；FI：HR=2.39，95% CI：1.61~3.54）及微血管并发症（PF：HR=1.66，95% CI：1.18~2.32；FI：HR=2.05，95% CI：1.47~2.86）风险升高相关。剂量-反应分析显示，虚弱程度增加与多种结局风险呈单调上升趋势，而PF评分与微血管并发症风险之间存在非线性关联。分层分析显示，FI与全因死亡的关联在收缩压（systolic blood pressure，SBP）较低或体重指数（body mass index，BMI）较低的患者中更为显著，而PF在不同亚组中的预测效应相对一致。敏感性分析结果与主分析基本一致。结论：在T1D患者中，虚弱与死亡及新发血管并发症风险增加显著相关。开展虚弱评估有助于识别预后较差的人群，并为T1D患者的风险分层和管理提供了依据。

Abstract

Objective：To investigate the associations between frailty status and the risks of mortality and vascular complications in adults with type 1 diabetes（T1D）. Methods：This prospective cohort study was based on the UK Biobank（UKB）and included participants with T1D at baseline. Frailty status was assessed using physical frailty（PF）and the frailty index（FI）. The primary outcomes included all-cause mortality，T1D-related and complication-related mortality，and incident macrovascular and microvascular complications. Cox proportional hazards regression models were used to evaluate the associations between frailty status and each outcome. Dose-response analyses，subgroup analyses，and multiple sensitivity analyses were further conducted. Results：A total of 1 571 participants with T1D at baseline were included in the mortality analyses，with a median follow-up of 13.4 years；among them，1 207 participants without baseline vascular complications were included in the complication analyses. Based on PF and FI，12.7% and 28.5% of participants were classified as frail，respectively. After multivariable adjustment，compared with non-frail participants，frail individuals had a significantly higher risk of all-cause mortality[PF：hazard ratio（HR）=2.76，95% confidence interval（CI）：1.92-3.98；FI：HR=2.71，95% CI：1.71-4.31]. The risk of T1D-related and complication-related mortality was also markedly increased among frail participants（PF：HR 4.02，95% CI：2.21-7.28；FI：HR 4.14，95% CI：1.73-9.89）. Among participants without baseline vascular complications，frailty was significantly associated with higher risks of incident macrovascular complications（PF：HR=2.17，95% CI：1.46-3.22；FI：HR=2.39，95% CI：1.61-3.54）and microvascular complications（PF：HR=1.66，95% CI：1.18-2.32；FI：HR=2.05，95% CI：1.47-2.86）. Dose-response analyses showed monotonic increases in the risks of multiple outcomes with increasing frailty severity，whereas a non-linear association was observed between PF scores and the risk of microvascular complications. Subgroup analyses showed that the association between FI and all-cause mortality was more pronounced among participants with lower systolic blood pressure（SBP）or lower body mass index（BMI），whereas the predictive effect of PF was relatively consistent across subgroups. Sensitivity analyses yielded results generally consistent with the main analyses. Conclusion：In adults with T1D，frailty was significantly associated with increased risks of mortality and incident vascular complications. Frailty assessment may help identify individuals at higher risk of poor prognosis and provide additional support for risk stratification and management in this population.

关键词

1型糖尿病 / 虚弱 / 死亡 / 糖尿病并发症 / UK Biobank

Key words

type 1 diabetes / frailty / mortality / diabetes complications / UK Biobank

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基金资助

国家自然科学基金(82230028)

国家“万人计划”青年拔尖人才支持计划(SQ2024QB05226)

江苏省前沿技术研发计划(BF2025612)

四大慢病重大专项(2023ZD0507400)

四大慢病重大专项(2023ZD0507403)