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


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 (1)H 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.
Bischof
M G
MG
Department of Internal Medicine III, Division of Endocrinology and Metabolism,Medical University of Vienna, Hanusch Hospital, A-1090 Vienna, Austria. martin.bischof@meduniwien.ac.at
Brehm
A
A
Bernroider
E
E
Krssák
M
M
Mlynárik
V
V
Krebs
M
M
Roden
M
M
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003401:Creatine / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004734:Energy Metabolism; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D018698:Glutamic Acid / Q000378:metabolism*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009778:Occipital Lobe / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D019382:Human Growth Hormone; D018698:Glutamic Acid; D005934:Glucagon; D005947:Glucose; D003401:Creatine; D006854:Hydrocortisone; D004837:Epinephrine