Cerebral glutamate metabolism during hypoglycaemia in healthy and type 1 diabetic humans

  1. M. G. Bischof1,
  2. A. Brehm1,
  3. E. Bernroider1,
  4. M. Krššák1,
  5. V. Mlynárik1,
  6. M. Krebs1,
  7. M. Roden2

Article first published online: 27 FEB 2006

DOI: 10.1111/j.1365-2362.2006.01615.x

Issue

European Journal of Clinical Investigation

European Journal of Clinical Investigation

Volume 36, Issue 3, pages 164–169, March 2006

Additional Information

How to Cite

Bischof, M. G., Brehm, A., Bernroider, E., Krššák, M., Mlynárik, V., Krebs, M. and Roden, M. (2006), Cerebral glutamate metabolism during hypoglycaemia in healthy and type 1 diabetic humans. European Journal of Clinical Investigation, 36: 164–169. doi: 10.1111/j.1365-2362.2006.01615.x

Author Information

  1. 1

    Medical University of Vienna,

  2. 2

    Hanusch Hospital, Vienna, Austria

* Martin Bischof, MD, Associate Professor of Medicine, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Tel/fax: +43 1 40400 7257; e-mail: martin.bischof@meduniwien.ac.at

Publication History

  1. Issue published online: 27 FEB 2006
  2. Article first published online: 27 FEB 2006
  3. Received 12 October 2005; accepted 11 January 2006

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Keywords:

  • Energy metabolism;
  • glutamate;
  • hypoglycaemia;
  • intracerebral glucose;
  • proton nuclear magnetic resonance spectroscopy;
  • type 1 diabetes

Abstract

Background  The mechanisms responsible for the progressive failure of hypoglycaemia counterregulation in long-standing type 1 diabetes are poorly understood. Increased brain glucose uptake during hypoglycaemia or alterations of brain energy metabolism could effect glucose sensing by the brain and thus contribute to hypoglycaemia-associated autonomic failure.

Materials and methods  Type 1 diabetic patients (T1DM) and healthy volunteers (CON) were studied before, during and after a hypoglycaemic (50 mg dL−1) hyperinsulinaemic (1·5 mU kg−1 min−1) clamp test. The 1H magnetic resonance spectroscopy of the occipital lobe of the brain was performed employing the STEAM localization technique. The water signal was suppressed by the modified SWAMP method. All spectra were acquired on a 3 Tesla scanner (80 cm MEDSPEC-DBX, Bruker Medical, Ettlingen, Germany) using a 10-cm diameter surface coil.

Results  During hypoglycaemia, T1DM showed blunted endocrine counterregulation. At baseline the brain tissue glucose : creatine ratio was lower in CON than in T1DM (CON 0·13 ± 0·05 vs. T1DM 0·19 0·11; P < 0·01). During hypoglycaemia glucose : creatine ratios decreased in both groups (CON 0·07 ± 0·08, P < 0·05; T1DM 0·03 ± 0·03, P < 0·001). A significant drop in the glutamate : creatine ratio could only be found in CON during hypoglycaemia (CON 1·36 ± 0·08 vs. 1·26 ± 0·11; P < 0·01; T1DM 1·32 ± 0·13 vs. 1·28 ± 0·15; P = NS). The ratios of glutamine, N-acetylaspartate, choline and myo-inositol : creatine were not different between both groups and did not change throughout the experiment.

Conclusions  Only in CON does moderate hypoglycaemia reduce intracerebral glutamate concentrations, possibly owing to a slower substrate flux through the tricarboxylic acid cycle in neurones. The maintenance of normal energy metabolism in T1DM during hypoglycaemia might effect glucose sensing in the brain and contribute to hypoglycaemia-associated autonomic failure.

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