Alteration of the regional cerebral glucose metabolism in healthy subjects by glucose loading.

High plasma glucose (PG) levels can reduce fluorine-18-labeled fluorodeoxyglucose ((18) F-FDG) uptake, especially in the Alzheimer's disease (AD)-related regions. This fact is supported by studies showing that the resting-state activity in diabetes can be altered in the default mode network (DMN)-related regions, which considerably overlap with the AD-related regions. In order to expand the current knowledge, we aimed to investigate the relationship between increasing PG levels and the regional cerebral metabolic rates for glucose (CMRglc ) as a direct index of brain activity. We performed dynamic (18) F-FDG positron emission tomography with arterial blood sampling once each in the fasting and glucose-loading conditions on 12 young, healthy volunteers without cognitive impairment or insulin resistance. The absolute CMRglc values were calculated for the volume-of-interest (VOI) analysis, and normalized CMRglc maps were generated for the voxelwise analysis. The normalized measurement is known to have smaller intersubject variability than the absolute measurement, and may, thus, lead to greater statistical power. In VOI analysis, no regional difference in the CMRglc was found between the two conditions. In exploratory voxelwise analysis, however, significant clusters were identified in the precuneus, posterior cingulate, lateral parietotemporal, and medial prefrontal regions where the CMRglc decreased upon glucose loading (P < 0.05, corrected). These regions include the representative components of both the DMN and AD pathology. Taken together with the previous knowledge on the relationships between the DMN, AD, and diabetes, it may be inferred that glucose loading induces hypometabolism in the AD-related and DMN-related regions. Hum Brain Mapp 37:2823-2832, 2016.