Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.
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.
Departments of Radiology and Nuclear Medicine School for Mental Health and Neuroscience (MHeNS) Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD Department of Psychiatry and Neuropsychology Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Frank C G
FCG
van Bussel
Walter H
WH
Backes
Paul A M
PAM
Hofman
Nicolaas A J
NAJ
Puts
Richard A E
RAE
Edden
Martin P J
MPJ
van Boxtel
Miranda T
MT
Schram
Coen D A
CDA
Stehouwer
Joachim E
JE
Wildberger
Jacobus F A
JFA
Jansen
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003071:Cognition; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001786:Blood Glucose; D018698:Glutamic Acid; D006442:Glycated Hemoglobin; D005680:gamma-Aminobutyric Acid; C517652:hemoglobin A1c protein, human