Background and Purpose—Diabetes type 2 (DM2) is associated with accelerated cognitive decline and structural brain abnormalities. Macrovascular disease has been described as a determinant for brain MRI changes in DM2, but little is known about the involvement of other DM2-related factors.

Methods—Brain MRI was performed in 1043 participants (151 DM2) with symptomatic arterial disease. Brain volumes were obtained through automated segmentation.

Results—Patients with arterial disease and DM2 had more global and subcortical brain atrophy (-1.20% brain/intracranial volume [95%CI -1.58 to -0.82], P<0.0005 and 0.20% ventricular/intracranial volume [0.05 to 0.34], P<0.01), larger WMH volumes (0.22 logtransformed volume [0.07 to 0.38], P<0.005), and more lacunar infarcts (OR 1.75 [1.13 to 2.69], P<0.01) than identical patients without DM2. In patients with DM2, high glucose levels (B-0.12% per mmol/L [-0.23 to -0.01], P<0.05) and diabetes duration (B-0.05% per year [-0.10 to -0.001], P<0.05) were associated with global brain atrophy.

Conclusion—In patients with symptomatic arterial disease, DM2 has an added detrimental effect on the brain. In patients with DM2, hyperglycemia and diabetes duration contribute to brain atrophy.