Clinical impacts of frailty on 123,172 people with diabetes mellitus considering the age of onset and drugs of choice: a nationwide population-based 10-year trajectory analysis

Frailty substantially increased the risk of adverse clinical outcomes, which was also critical in diabetes management. This study aimed to investigate the interrelationships between the age of onset, frailty, anti-diabetic medications and clinical outcomes in people with diabetes mellitus (DM).A total of 123,172 people aged 40 years and older who were newly diagnosed with DM were identified and categorised into four frailty subgroups (robust, mild, moderate and severe) based on the multimorbidity frailty index (mFI). Cox proportional hazards models were used to examine associations between frailty and clinical outcomes at different ages of DM onsets (40-64, 65-74, 75-84 and 85+ years). Outcomes of interest included generic outcomes (mortality and unplanned hospitalisation) and DM-related outcomes (cardiovascular disease-related mortality, major adverse cardiovascular events (MACEs), diabetes-related hospitalisation and hypoglycaemia).The proportion of frailty increased with age at diagnosis amongst people with incident DM and the mFI scores increased significantly during the 10-year follow-up. Amongst people with diabetes, those with mild, moderate and severe frailty were associated with greater risks of all-cause mortality (mild: adjusted hazard ratio (aHR) 1.69 [95% confidence interval (CI) 1.60-1.80], P < 0.01; moderate: aHR 2.46 [2.29-2.65], P < 0.01; severe frailty: aHR 3.40 [3.16-3.65], P < 0.01) compared with the robust group. Similar results were found in unplanned hospitalisations, cardiovascular disease-related mortality, MACEs and hypoglycaemia.Our study quantified the prevalence of frailty, captured its dynamic changes and examined its impacts on various clinical outcomes amongst people with diabetes at different ages at onset. Frailty assessment and management should be implemented into routine diabetes care.