Type 2 diabetes mellitus is associated with accelerated
cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that
insulin signaling modulates
neurotransmitter activity, including inhibitory γ-
aminobutyric acid (
GABA) and excitatory
glutamate (Glu) receptors. Therefore, we examined whether levels of
GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with
type 2 diabetes and 39 participants without
type 2 diabetes underwent detailed cognitive assessments and 3-Tesla
proton MR spectroscopy. The associations of
neurotransmitters with
type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with
type 2 diabetes, in participants with higher fasting
blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with
type 2 diabetes have alterations in the GABAergic
neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.