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

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

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.

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Cognition*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / psychology*
  • Female
  • Glutamic Acid / metabolism
  • Glycated Hemoglobin / metabolism
  • Gray Matter / diagnostic imaging
  • Gray Matter / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • White Matter / diagnostic imaging
  • White Matter / metabolism
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Glutamic Acid
  • gamma-Aminobutyric Acid