Elevated brain glutamate levels in type 1 diabetes: correlations with glycaemic control and age of disease onset but not with hypoglycaemia awareness status

Diabetologia. 2019 Jun;62(6):1065-1073. doi: 10.1007/s00125-019-4862-9. Epub 2019 Apr 19.


Aims/hypothesis: Chronic hyperglycaemia in type 1 diabetes affects the structure and functioning of the brain, but the impact of recurrent hypoglycaemia is unclear. Changes in the neurochemical profile have been linked to loss of neuronal function. We therefore aimed to investigate the impact of type 1 diabetes and burden of hypoglycaemia on brain metabolite levels, in which we assumed the burden to be high in individuals with impaired awareness of hypoglycaemia (IAH) and low in those with normal awareness of hypoglycaemia (NAH).

Methods: We investigated 13 non-diabetic control participants, 18 individuals with type 1 diabetes and NAH and 13 individuals with type 1 diabetes and IAH. Brain metabolite levels were determined by analysing previously obtained 1H magnetic resonance spectroscopy data, measured under hyperinsulinaemic-euglycaemic conditions.

Results: Brain glutamate levels were higher in participants with diabetes, both with NAH (+15%, p = 0.013) and with IAH (+19%, p = 0.003), compared with control participants. Cerebral glutamate levels correlated with HbA1c levels (r = 0.40; p = 0.03) and correlated inversely (r = -0.36; p = 0.04) with the age at diagnosis of diabetes. Other metabolite levels did not differ between groups, apart from an increase in aspartate in IAH.

Conclusions/interpretation: In conclusion, brain glutamate levels are elevated in people with type 1 diabetes and correlate with glycaemic control and age of disease diagnosis, but not with burden of hypoglycaemia as reflected by IAH. This suggests a potential role for glutamate as an early marker of hyperglycaemia-induced cerebral complications of type 1 diabetes. ClinicalTrials.gov NCT03286816; NCT02146404; NCT02308293.

Keywords: 1H MRS; Brain; Euglycaemia; Glutamate; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Brain / metabolism*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Glucose Clamp Technique
  • Glutamic Acid / metabolism*
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Young Adult


  • Blood Glucose
  • Glutamic Acid

Associated data

  • ClinicalTrials.gov/NCT03286816
  • ClinicalTrials.gov/NCT02146404
  • ClinicalTrials.gov/NCT02308293