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

## TL;DR

This study finds that diabetes and frailty together increase mortality risk in older adults, with a stronger combined effect in women.

## Contribution

The study identifies sex-specific differences in the combined mortality risk of diabetes and frailty.

## Key findings

- Mortality risk is highest in older adults with both diabetes and frailty.
- An additive interaction between diabetes and frailty is observed only in women.
- Frailty alone poses a higher mortality risk in men compared to women.

## Abstract

Diabetes 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.

The 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.

Of 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).

Diabetes 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.