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Background <p>Although frailty has been associated with individual components of cardiovascular-kidney-metabolic (CKM) syndrome, the overall relationship between frailty and CKM syndrome, as well as the potential mediating role of insulin resistance (IR), remains inadequately understood.</p> Methods <p>We analyzed data from 4,615 adults aged ≥ 45 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2025. Frailty status was evaluated using the Frailty Index (FI) and classified into three categories: robust, prefrail, and frail. Changes in frailty over time were measured based on frailty status at baseline and during a follow-up survey conducted four years later. Logistic regression, linear regression, and bootstrap analyses were employed to examine the association between frailty and progression to advanced CKM stages, as well as the mediating role of the estimated glucose disposal rate (eGDR) as a proxy for IR.</p> Results <p>Individuals who remained in or progressed to pre-frail or frail states during the study period exhibited significantly increased risks of developing advanced CKM syndrome. In the fully adjusted model, the highest risk of CKM syndrome was observed among individuals who remained consistently pre-frail or frail (OR = 3.80; 95% CI: 2.67–5.46;<i>P</i> &lt; 0.001), followed by those who transitioned from a robust state to a worse frailty category (OR = 3.08; 95% CI: 2.13–4.48;<i>P</i> &lt; 0.001). Furthermore, greater increases in the Frailty Index (ΔFI) and higher overall FI scores were significantly associated with an elevated risk of CKM syndrome (ΔFI: OR = 2.12; 95% CI: 1.51–2.98; FI score: OR = 2.19; 95% CI: 1.54–3.11; <i>P</i> &lt; 0.001), after full adjustment.Mediation analysis indicated that IR accounted for approximately 31.6% of the total effect of frailty on the development of CKM syndrome.</p> Conclusion <p>Both baseline frailty and its progression over time were independently associated with an elevated risk of advanced CKM syndrome. IR was identified as a partial mediator in this relationship. This finding suggests that IR may serve as a modifiable biological target for intervention.</p>

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Longitudinal changes in frailty, insulin resistance and incident cardiovascular-kidney- metabolic syndrome progression in middle-aged and older adults: evidence from CHARLS

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月27日

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  • Qi Huang,
  • Xian Luo,
  • Tao Yang,
  • XiaoMan Qing,
  • XinMei Zhang,
  • MingZhu Xiu,
  • Zheng Liu,
  • Hao Li,
  • Sha Liu,
  • Wanmeng Xiao,
  • Muhan Lü,
  • Song Su

摘要

Background

Although frailty has been associated with individual components of cardiovascular-kidney-metabolic (CKM) syndrome, the overall relationship between frailty and CKM syndrome, as well as the potential mediating role of insulin resistance (IR), remains inadequately understood.

Methods

We analyzed data from 4,615 adults aged ≥ 45 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2025. Frailty status was evaluated using the Frailty Index (FI) and classified into three categories: robust, prefrail, and frail. Changes in frailty over time were measured based on frailty status at baseline and during a follow-up survey conducted four years later. Logistic regression, linear regression, and bootstrap analyses were employed to examine the association between frailty and progression to advanced CKM stages, as well as the mediating role of the estimated glucose disposal rate (eGDR) as a proxy for IR.

Results

Individuals who remained in or progressed to pre-frail or frail states during the study period exhibited significantly increased risks of developing advanced CKM syndrome. In the fully adjusted model, the highest risk of CKM syndrome was observed among individuals who remained consistently pre-frail or frail (OR = 3.80; 95% CI: 2.67–5.46;P < 0.001), followed by those who transitioned from a robust state to a worse frailty category (OR = 3.08; 95% CI: 2.13–4.48;P < 0.001). Furthermore, greater increases in the Frailty Index (ΔFI) and higher overall FI scores were significantly associated with an elevated risk of CKM syndrome (ΔFI: OR = 2.12; 95% CI: 1.51–2.98; FI score: OR = 2.19; 95% CI: 1.54–3.11; P < 0.001), after full adjustment.Mediation analysis indicated that IR accounted for approximately 31.6% of the total effect of frailty on the development of CKM syndrome.

Conclusion

Both baseline frailty and its progression over time were independently associated with an elevated risk of advanced CKM syndrome. IR was identified as a partial mediator in this relationship. This finding suggests that IR may serve as a modifiable biological target for intervention.