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

Frank 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, Jaap Jansen*

*Corresponding author for this work

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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 -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 HbA(1c) levels, and higher GABA+ levels in participants with both high HbA(1c) 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.
Original languageEnglish
Article numbere4803
Number of pages6
JournalMedicine
Volume95
Issue number36
DOIs
Publication statusPublished - Sep 2016

Keywords

  • -aminobutyric acid
  • cognition
  • glutamate
  • magnetic resonance spectroscopy
  • type 2 diabetes mellitus

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