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Medicine (Baltimore). 2016 Sep;95(36):e4803. doi: 10.1097/MD.0000000000004803.

Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.

Author information

1
aDepartments of Radiology and Nuclear Medicine bSchool for Mental Health and Neuroscience (MHeNS) cCardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands dRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine eF.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD fDepartment of Psychiatry and Neuropsychology gDepartment of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.

Abstract

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.

PMID:
27603392
PMCID:
PMC5023915
DOI:
10.1097/MD.0000000000004803
[Indexed for MEDLINE]
Free PMC Article

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