Association between glycated hemoglobin A1c levels, control status, and cognitive function in type 2 diabetes: a prospective cohort study

Cognitive impairment (CI) is a common complication in patients with type 2 diabetes mellitus (T2DM), but its relationship with long-term glycemic control remains unclear. This study aimed to investigate the associations between mean hemoglobin A1c (HbA1c) levels, HbA1c control status, HbA1c fluctuations, and CI in Chinese adults aged 45 years and older with T2DM using data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 797 participants with HbA1c measurements from 2011 to 2015 and cognitive function assessments in 2018 were included. Logistic regression models and restricted cubic spline (RCS) analysis were applied, adjusting for potential confounders. Higher mean HbA1c levels (≥ 9%) were significantly associated with an increased risk of CI, particularly in global cognition and episodic memory (OR 4.03 (1.45-11.20) for global cognition; OR 2.92 (1.02-8.38) for episodic memory). RCS analysis revealed a U-shaped relationship between mean HbA1c and CI, indicating that both excessively low and high HbA1c levels elevate CI risk. Uncontrolled HbA1c levels (≥ 8%) were also linked to higher CI risk compared to stable HbA1c levels. Maintaining HbA1c levels below 8% may significantly reduce CI risk in T2DM patients, highlighting the importance of personalized glycemic management.