Since hyperhomocysteinaemia (HHcys) is implicated as a risk factor for the development of neurodegeneration, and is associated with the development of metabolic diseases,we aimed at analysing the effect of homocysteine (Hcys) on regional fluorine-18-fluorodeoxyglucose (18F-FDG) brain metabolismin 51 controlled type 2 diabetic and in 48 non-DM obese participants. Plasma Hcys levels were measured by an immunoassay. Homocysteine-related 18F-FDG regional brain metabolism was evaluated applying 18F-FDG PET/CT using magnetic resonance imaging (MRI)-based brain template for statistical parametric mapping (SPM) analysis. Homocysteine-related decreased 18F-FDG uptake was shown in the right middle temporal gyrus in the whole population. Diabetics with Hcys above the reference limit expressed decreased glucose metabolismin the left calcarine cortex compared to the obese with HHcys. Regional metabolic alterations evoked on the basis of HHcys draw attention to the potential risk of neurodegeneration caused by metabolic disturbances.