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

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.
AuthorsFrank C G van Bussel, Walter H Backes, Paul A M Hofman, Nicolaas A J Puts, Richard A E Edden, Martin P J van Boxtel, Miranda T Schram, Coen D A Stehouwer, Joachim E Wildberger, Jacobus F A Jansen
JournalMedicine (Medicine (Baltimore)) Vol. 95 Issue 36 Pg. e4803 (Sep 2016) ISSN: 1536-5964 [Electronic] United States
PMID27603392 (Publication Type: Journal Article)
Chemical References
  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Glutamic Acid
  • gamma-Aminobutyric Acid
Topics
  • Aged
  • Blood Glucose (metabolism)
  • Case-Control Studies
  • Cognition
  • Cognitive Dysfunction (etiology, metabolism)
  • Diabetes Mellitus, Type 2 (physiopathology, psychology)
  • Female
  • Glutamic Acid (metabolism)
  • Glycated Hemoglobin (metabolism)
  • Gray Matter (diagnostic imaging, metabolism)
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • White Matter (diagnostic imaging, metabolism)
  • gamma-Aminobutyric Acid (metabolism)

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