Type 2 Diabetes, Skin Autofluorescence, and Brain Atrophy

Type 2 Diabetes Mellitus (T2DM) is associated with brain atrophy, but the mechanisms underlying this link are unknown. Advanced glycation end products (AGEs) accumulate in T2DM resulting in inflammation, oxidative stress, and protein cross-linking, which are known contributors to neurodegeneration. We aimed to study whether tissue AGE accumulation is associated with T2DM-related brain atrophy. We performed brain magnetic resonance imaging (MRI), cognitive tests and non-invasive skin autofluorescence (SAF, a measure of tissue AGE levels) on people aged >55 years with and without T2DM. Multivariable linear regression was used to study the relationships between T2DM, SAF and gray matter volume. There were 486 people included in the study. T2DM was associated with greater SAF. Greater SAF, T2DM and cognitive impairment were each associated with lower gray matter volume independently of age, sex and total intracranial volume. SAF partially mediated the association between T2DM and gray matter volume. Longitudinal studies may help confirm whether tissue AGE accumulation is associated with brain atrophy in T2DM.