Objective: We investigated type 2 diabetes mellitus (T2DM) as a risk factor for brain atrophy and glucose hypometabolism in older adults with or at risk of cognitive impairment. Methods: Participants with the T2DM were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1/GO/2 cohorts). Analysis of covariance models were used to compare participants with and without T2DM, controlling for potential confounding factors. Results: Whole brain volume and whole brain [ 18 F]-fluorodeoxyglucose (FDG) uptake were significantly different as a function of T2DM status, independent of baseline clinical diagnosis. On post hoc analysis, a lower whole brain volume was seen in participants with both mild cognitive impairment (MCI) and T2DM (n 76) compared with participants who had MCI but not T2DM (n 747; p 0.009). Similarly, mean FDG uptake in gray matter and white matter was lower in participants with both MCI and T2DM (n 72) than in participants with MCI without T2DM (n 719; p 0.04). Subsequent regional analysis revealed that the decreased FDG uptake in participants with both MCI and T2DM was mainly manifested in 3 brain regions: frontal lobe, sensory motor cortex, and striatum. Conclusions: T2DM may accelerate cognition deterioration in patients with MCI by affecting glucose metabolism and brain volume.