Depressive symptoms are associated with the incidence of frailty in older adults with cardiometabolic diseases: Interaction between depression and diabetes.
Depressive symptoms were independently associated with incident frailty (by both mCHS and KCL criteria) in older outpatients with cardiometabolic diseases, and a significant interaction between depressive symptoms and diabetes suggests that patients with both may be a high-risk group for incident frailty.
Key Findings
Results
Depressive symptoms (GDS-15 ≥ 5) were independently associated with incident frailty defined by both the modified Cardiovascular Health Study (mCHS) criteria and the Kihon Checklist (KCL).
Longitudinal analysis of 431 outpatients aged 65 years or older with cardiometabolic diseases attending a frailty clinic from 2015 to 2023.
Median follow-up was 2.9 years; depressive symptoms were assessed with the Geriatric Depression Scale (GDS)-15.
The association was significant across all multivariable Cox regression models for both frailty definitions.
Results
Fully adjusted hazard ratios for incident frailty with depressive symptoms were 1.92 for mCHS-defined frailty and 2.05 for KCL-defined frailty.
Hazard ratios and 95% CIs were estimated using multivariable Cox regression models.
The associations held after full covariate adjustment.
Results
The association between depressive symptoms and incident frailty was consistent in participants with diabetes and with hyperglycemia in stratified analyses.
Stratified analyses were performed to see whether comorbidities modified the association.
Consistent associations were seen in the diabetes and hyperglycemia strata.
Results
There were significant interactions between depressive symptoms and diabetes for both mCHS- and KCL-defined incident frailty.
The interaction was observed for both frailty definitions.
The authors interpret this as suggesting that patients with coexisting depressive symptoms and diabetes may be a high-risk group for incident frailty.
Results
No significant interactions were observed between depressive symptoms and cognitive impairment or physical inactivity for incident frailty.
These were tested as other potential effect modifiers alongside diabetes.
Only the interaction with diabetes was significant.
Conclusions
The authors conclude that further studies are needed to determine whether interventions targeting depressive symptoms and diabetes management can reduce incident frailty risk.
The study is observational and cannot establish whether treating depression or diabetes would reduce frailty.
The population was outpatients at a frailty clinic with cardiometabolic diseases.
What This Means
This study followed 431 older adults (65 or older) with heart and metabolic conditions such as diabetes who attended a frailty clinic in Japan. Researchers measured depressive symptoms with a short questionnaire and then tracked who developed frailty, a state of reduced strength and resilience, over a median of about 2.9 years. Frailty was judged in two ways: a physical-performance-based set of criteria and a questionnaire-based checklist.
People with depressive symptoms were roughly twice as likely to develop frailty as those without, with adjusted hazard ratios of 1.92 and 2.05 depending on how frailty was defined. The link was especially notable for people with diabetes: the analysis found that depressive symptoms and diabetes interacted, meaning the combination appeared to carry additional risk. No such interaction was found for cognitive impairment or physical inactivity.
This research suggests that older adults who have both depressive symptoms and diabetes may be a group worth particular attention for frailty prevention. However, because this was an observational study in a specific clinic population, it cannot show that treating depression or improving diabetes care would prevent frailty. The authors note that further studies are needed to test that.
Kobayashi F, Tamura Y, Murao Y, Toyoshima K, Oba K, Kodera R, et al.. (2026). Depressive symptoms are associated with the incidence of frailty in older adults with cardiometabolic diseases: Interaction between depression and diabetes.. PloS one. https://doi.org/10.1371/journal.pone.0360802