AUTHOR=Mielke Nina , Barghouth Muhammad Helmi , Schneider Alice , Ferrari Damiano , Kaiser Janine , Ebert Natalie , Schaeffner Elke 

TITLE=Sex differences in the combined effect of diabetes and frailty on all-cause mortality in community-dwelling older adults

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1670278

DOI=10.3389/fendo.2025.1670278

ISSN=1664-2392

ABSTRACT=IntroductionDiabetes and frailty are common in older adults and independently associated with all-cause mortality. Sex-stratified analyses indicate that the mortality risk associated with frailty is higher in men, whereas that associated with diabetes is higher in women. This study investigates sex differences in the combined effect of diabetes and frailty on mortality.MethodsThe Berlin Initiative (cohort) study assessed frailty and diabetes at the third follow-up visit. Participants (women and men ≥75 years) were categorized by frailty and diabetes status and followed-up until death or dataset closure (March 2023; median follow-up 6.0 years). Sex-stratified Cox regressions estimated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality. Interaction between frailty and diabetes on mortality was analysed.ResultsOf 1143 participants (mean age 84 years; 55% women), baseline characteristics were similar between sexes, with fewer women having a partner (33% vs. 70%) or cardiovascular disease (67% vs. 77%). Mortality risk increased from non-frail individuals with diabetes (HR, 95% CI: women 1.25, 0.76-2.06 vs. men 1.56, 1.08-2.24) to those with frailty alone (HR 95% CI: women 1.81, 1.26- 2.59 vs. men 2.52, 1.78-3.57) and was highest among those with both conditions (HR 95% CI: women 3.39, 2.19-5.24; men 3.42, 2.28-5.14). An indication of additive interaction between frailty and diabetes on mortality was only found in women (RERI 1.32, 95% CI 0-2.65).ConclusionsDiabetes and frailty increase mortality risk in both older women and men, with an additive interaction in women. These findings support sex-specific risk stratification and emphasize the need for mechanistic research to inform targeted interventions.