TY - JOUR
T1 - Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning
AU - van Bussel, Frank C. G.
AU - Backes, Walter H.
AU - Hofman, Paul A. M.
AU - Puts, Nicolaas A. J.
AU - Edden, Richard A. E.
AU - van Boxtel, Martin P. J.
AU - Schram, Miranda T.
AU - Stehouwer, Coen D. A.
AU - Wildberger, Joachim E.
AU - Jansen, Jaap
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - -aminobutyric acid
KW - cognition
KW - glutamate
KW - magnetic resonance spectroscopy
KW - type 2 diabetes mellitus
U2 - 10.1097/MD.0000000000004803
DO - 10.1097/MD.0000000000004803
M3 - Article
C2 - 27603392
SN - 0025-7974
VL - 95
JO - Medicine
JF - Medicine
IS - 36
M1 - e4803
ER -