The effects of long-term cumulative HbA1c exposure on the development and onset time of dementia in the patients with type 2 diabetes mellitus: Hospital based retrospective study (2005–2021)

•Our study is the first to show the effect of cumulative HbA1c (AUCHbA1c) and mean HbA1c over time (HbA1cavg) on dementia.•Prior studies have focused on the diagnosis of T2DM or single-time HbA1c in association with development of dementia, while we examined the effects of long-term cumulative glycemic exposure.•Our study suggests poorly controlled diabetes may increase the risk of developing dementia and shorten the time to onset of dementia based on the levels of AUCHbA1c and HbA1cavg. We examined cumulative effects of long-term glycemic exposure in patients with type 2 diabetes mellitus (T2DM) on the development of dementia. The study involved 20,487 records of patients with T2DM identified in the electronic medical record at Severance Hospital, Korea. Cumulative HbA1c (AUCHbA1c) and mean HbA1c over time (HbA1cavg) as measures of long-term glycemic exposure were compared for the development of dementia and the time to dementia. AUCHbA1c and HbA1cavg were significantly higher in patients who later developed dementia than in those who did not (AUCHbA1c: 56.2 ± 26.4 vs. 52.1 ± 26.1 %Year; HbA1cavg: 7.3 ± 1.0 vs. 7.0 ± 1.0%). Odds ratio of dementia increased when HbA1cavg was 7.2% (55 mmol/mol) or above, and when AUCHbA1c was 42 %Year (e.g., HbA1c 7.0% maintained for 6 years) or above. Among those who developed dementia, as HbA1cavg increased, the time to dementia onset decreased (β = -380.6 days, 95% confidence interval [CI]: −416.2 to −345.0). Our results indicate poorly controlled T2DM was associated with an increased risk of developing dementia, as measured by AUCHbA1c and HbA1cavg. Higher cumulative glycemic exposure may lead to developing dementia in a shorter time.