Objective
We aim to investigate the associations of glucose metabolism status with brain macro- and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics.
Methods
This study enrolled 29,251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c < 7%, and T2D with HbA1c ≥ 7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid (CSF), and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts. Multivariable linear regression models were used to estimate β values and 95% confidence intervals (CIs).
Results
After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes compared with participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P-trend <0.05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P-trend <0.05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (β [95%CI]: -0.04 [-0.08, -0.003]). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P-trend <0.05), except for FA values in projection fibers.
Interpretation
These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.
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