The authors of this study at a large hospital in South Korea sought to assess the cumulative effect of long-term glycaemic exposure on the risk of dementia in people with type 2 diabetes. A total of 20 487 adults with type 2 diabetes newly diagnosed between November 2005 and June 2021 were evaluated; participants aged <50 years, those with less than 3 years of follow-up and those who had fewer than two HbA1c measurements over the study period were excluded.
HbA1c area under the curve (AUC) from first to final HbA1c measurement was used to estimate cumulative glycaemic exposure, alongside mean HbA1c over time (calculated from the AUC and the measurement time). The primary outcome was development of dementia according to ICD-10 coding, and the secondary outcome was the time between type 2 diabetes diagnosis and the onset of dementia.
Of the 20 487 participants, 1072 (5.2%) developed dementia over the follow-up period. There was no significant association between HbA1c at diagnosis and risk of dementia. In contrast, both AUC and mean HbA1c over time were significantly higher in those who developed dementia. An 11 mmol/mol increase in mean HbA1c over time increased the risk of dementia by 43%. Compared with a mean HbA1c of 53 mmol/mol, a mean of ≥86 mmol/mol was associated with a 288% increase in risk.
There was a linear relationship between mean HbA1c and the time to dementia onset, with each 11 mmol/mol increase shortening the time by 381 days.
The authors conclude that long-term glycaemic exposure in people with type 2 diabetes is associated with both increased risk of and reduced time to development of dementia. Efforts to keep glycaemic exposure to the lowest possible level should be encouraged to minimise this risk.