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)

Aims: We examined cumulative effects of long-term glycemic exposure in patients with type 2 diabetes mellitus (T2DM) on the development of dementia. Methods: The study involved 20,487 records of patients with T2DM identified in the electronic medical record at Severance Hospital, Korea. Cumulative HbA1c (AUC_HbA1c) and mean HbA1c over time (HbA1c_avg) as measures of long-term glycemic exposure were compared for the development of dementia and the time to dementia. Results: AUC_HbA1c and HbA1c_avg were significantly higher in patients who later developed dementia than in those who did not (AUC_HbA1c: 56.2 ± 26.4 vs. 52.1 ± 26.1 %Year; HbA1c_avg: 7.3 ± 1.0 vs. 7.0 ± 1.0%). Odds ratio of dementia increased when HbA1c_avg was 7.2% (55 mmol/mol) or above, and when AUC_HbA1c was 42 %Year (e.g., HbA1c 7.0% maintained for 6 years) or above. Among those who developed dementia, as HbA1c_avg increased, the time to dementia onset decreased (β = -380.6 days, 95% confidence interval [CI]: −416.2 to −345.0). Conclusions: Our results indicate poorly controlled T2DM was associated with an increased risk of developing dementia, as measured by AUC_HbA1c and HbA1c_avg. Higher cumulative glycemic exposure may lead to developing dementia in a shorter time.