Excess hypoglycaemia-related hospitalisation in older adults with comorbid type 2 diabetes and dementia: a UK Biobank cohort study

Background: Older adults living with both type 2 diabetes mellitus (T2DM) and dementia may be especially vulnerable to severe hypoglycaemia because cognitive impairment complicates glucose monitoring, medication management and recognition of glycaemic symptoms. It remains unclear whether the combined conditions confer an excess risk of hypoglycaemia-related hospitalisation beyond the risks associated with either condition alone. Aim: To determine whether comorbid T2DM and dementia are associated with excess hypoglycaemia-related hospitalisation. Secondary aims were to characterise overall hospital admissions, falls-related admissions, hyperglycaemia-related admissions and mortality across disease states. Methods: We analysed retrospective longitudinal UK Biobank data for 329,566 participants aged 65 years or older. T2DM and dementia were modelled as time-varying exposures. Recurrent hospital admissions were analysed using Prentice-Williams-Peterson total-time models and mortality using a time-dependent Cox model, adjusted for sex and socioeconomic deprivation. We reported joint effects, condition-specific effects and interaction on multiplicative and additive scales; additive interaction was quantified using the relative excess risk due to interaction (RERI). Results: By the end of follow-up, 18,397 participants (5.6%) had developed T2DM only, 6,214 (1.9%) dementia only and 802 (0.2%) both conditions. Hypoglycaemia-related hospitalisation occurred in 6.61% of participants while living with both conditions, compared with 1.88% with T2DM only, 0.91% with dementia only and 0.15% with neither condition. Relative to neither condition, the adjusted hazard ratio (HR) was 21.28 (95% CI 17.76 to 25.50) for T2DM only, 14.73 (10.47 to 20.71) for dementia only and 104.94 (73.79 to 149.24) for comorbidity. T2DM increased the hypoglycaemia admission hazard among people with dementia (HR 7.13, 4.63 to 10.97), while dementia increased it among people with T2DM (HR 4.93, 3.60 to 6.76). The positive additive interaction was substantial (RERI 69.93, 35.17 to 104.68; p<0.001), although interaction was sub-multiplicative (HR 0.33, 0.21 to 0.53). Comorbidity was also associated with the highest overall admission, falls and mortality burden, but these outcomes did not show clear positive additive interactions. Conclusion: Hypoglycaemia-related hospitalisation was the principal excess comorbid outcome in older adults with T2DM and dementia. The combined hazard substantially exceeded that expected from adding the separate relative hazards associated with each condition. General admissions, falls and mortality were also elevated in the comorbid state, corroborating existing evidence and indicating wider clinical vulnerability. These findings support prioritising safer, cognitively appropriate glycaemic management in this high-risk population.