Front Med (Lausanne). 2025 Dec 22;12:1617556. doi: 10.3389/fmed.2025.1617556. eCollection 2025.
ABSTRACT
INTRODUCTION: Frailty is a common adverse outcome in diabetes that is linked to reduced quality of life and increased mortality and is strongly associated with insulin resistance. However, the relationship between long-term cumulative insulin resistance and frailty progression remains unclear, particularly in Chinese adults with diabetes.
METHODS: We used data from the China Health and Retirement Longitudinal Study. We included 451 participants aged 45 years or older with baseline diabetes in 2011 who had frailty index scores based on 26 health deficit items across four waves (2011, 2015, 2018, 2020) and complete data in 2011 and 2015 to calculate cumulative estimated glucose disposal rate, cumulative triglyceride-glucose index, and cumulative triglyceride-glucose-body mass index. Linear mixed-effects models with random intercepts, adjusted for baseline age, sex, smoking, alcohol consumption, baseline estimated glucose disposal rate, and cardiovascular disease history, were used to examine the interaction between standardized cumulative indices and time in years on frailty index trajectories. Prespecified subgroup interactions were also evaluated.
RESULTS: Only the interaction between cumulative estimated glucose disposal rate and time was statistically significant. A higher cumulative estimated glucose disposal rate was associated with a slower annual increase in frailty index (interaction beta = -0.0019 per year, 95% confidence interval -0.0035 to -0.0002, P = 0.028), whereas cumulative triglyceride-glucose index and cumulative triglyceride-glucose-body mass index were not associated with the rate of frailty change. Subgroup analyses did not identify statistically significant effect modification by sex, age group, baseline frailty level, baseline cardiovascular disease, residence, or education.
DISCUSSION: Higher cumulative estimated glucose disposal rate, reflecting better sustained insulin sensitivity over four years, was associated with a slower nine-year frailty progression among middle-aged and older Chinese adults with diabetes. Although the effect size is modest and causality cannot be inferred, cumulative estimated glucose disposal rate may serve as a useful indicator for long-term risk assessment and longitudinal monitoring of frailty.
PMID:41497955 | PMC:PMC12767217 | DOI:10.3389/fmed.2025.1617556