Aim Diabetes mellitus (DM) is associated with brain atrophy and vascular brain lesions. Cardiovascular disease is a key determinant in this association. We assessed whether DM increased the rate of progression of brain atrophy, vascular brain lesions, and cognitive decline in patients with symptomatic atherosclerotic disease. Methods In 663 patients (58 ± 10 years) from the SMART-MR study (n = 89 with DM), 1.5 T MRI and neuropsychological examination were performed at baseline and after 3.9 ± 0.4 years follow-up. Results Repeated measures ANCOVA (adjusted for age, sex, and vascular risk factors) showed that patients with DM had smaller total brain volume (mean differences as percentage of intracranial volume (ICV) [95% CI]: - 1.36% [- 1.81; - 0.91]), smaller gray matter volume (- 1.23% [- 1.85; - 0.61]), larger ventricular volume (0.32% [0.14; 0.49]), and larger white matter lesion volume (0.31% [0.09; 0.53]) than patients without DM. Patients with DM had accelerated increase in ventricular volume over time compared with patients without DM (mean differences ventricular volume as percentage of ICV: 0.32% [0.25; 0.39] vs. 0.17% [0.15; 0.19]; p-interaction DM × time < 0.01). Poisson regression showed that patients with DM had an increased risk for incident brain infarcts (relative risk [95% CI]: 1.62 [1.04; 2.53]). Patients with and without DM had similar performance on cognition. Conclusions DM on top of existing symptomatic atherosclerotic disease is associated with increased brain atrophy and vascular brain lesion load that proceed at a slightly higher rate than in patients without DM. © 2013 Elsevier B.V.