Associations of long-term average and variability of estimated glucose disposal rate with frailty progression: evidence from two prospective cohorts

BACKGROUND: The estimated glucose disposal rate (eGDR), when measured at a single time point, has been linked to frailty. This study aimed to investigate the associations between long-term eGDR patterns and frailty progression. METHODS: We conducted prospective analyses among participants aged ≥ 45 years from two cohorts: the Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA). Two metrics were derived to characterize long-term eGDR patterns over an 8-year exposure period: average eGDR and eGDR variability (assessed by variation independent of the mean [VIM]). The frailty index (FI, 0-100 points) was calculated every two years during the follow-up period, with higher scores indicating more severe frailty. Linear mixed-effects models were used to analyze the associations of long-term eGDR patterns with frailty progression. RESULTS: This study included 6,829 participants from HRS (mean age: 67.7 years, 60.0% females) and 2,152 participants from ELSA (mean age: 69.7 years, 56.5% females). Compared with individuals in the lowest tertile (T1) of average eGDR, those in the highest tertile (T3) showed a significantly slower increase in FI over time (pooled β: -0.347, 95% CI: -0.536 to -0.157; I² = 58.6%). For each 1-standard deviation (SD) increase in average eGDR, the pooled β value was -0.139 (95% CI: -0.203 to -0.075; I² = 40.2%). Conversely, independent of the average eGDR level, higher eGDR variability (T3 vs. T1 of VIM) was associated with accelerated FI progression (pooled β: 0.226, 95% CI: 0.107 to 0.346; I² = 0.0%). Each 1-SD increase in eGDR variability was associated with an additional annual FI increase of 0.076 (pooled β: 0.076, 95% CI: 0.027 to 0.124; I² = 0.0%). CONCLUSIONS: Both long-term average and variability of eGDR were associated with frailty progression, highlighting the importance of monitoring eGDR dynamics and implementing interventions to stabilize eGDR in aging populations.