Aims/hypothesis
This study aimed to examine brain energy metabolism during moderate insulin-induced hypoglycaemia in Type 1 diabetic patients and healthy volunteers.Methods
Type 1 diabetic patients (mean diabetes duration 13±2.5 years; HbA1c 6.8±0.3%) and matched controls were studied before, during (0–120 min) and after (120–240 min) hypoglycaemic (~3.0 mmol/l) hyperinsulinaemic (1.5 mU·kg–1·min–1) clamp tests. Brain energy metabolism was assessed by in vivo 31P nuclear magnetic resonance spectroscopy of the occipital lobe (3 Tesla, 10-cm surface coil).Results
During hypoglycaemia, the diabetic patients showed blunted endocrine counter-regulation. Throughout the study, the phosphocreatine:
-ATP ratios were lower in the diabetic patients (baseline: controls 3.08±0.29 vs diabetic patients 2.65±0.43,
p<0.01; hypoglycaemia: 2.97±0.38 vs 2.60±0.35,
p<0.05; recovery: 3.01±0.28 vs 2.60±0.35,
p<0.01). Intracellular pH increased in both groups, being higher in diabetic patients (7.096±0.010 vs. 7.107±0.015,
p<0.04), whereas intracellular magnesium concentrations decreased in both groups (controls: 377±33 vs 321±39; diabetic patients: 388±47 vs 336±68 µmol/l;
p<0.05).
Conclusions/interpretation
Despite a lower cerebral phosphocreatine:
-ATP ratio in Type 1 diabetic patients at baseline, this ratio does not change in control or diabetic patients during modest hypoglycaemia. However, both groups exhibit subtle changes in intracellular pH and intracellular magnesium concentrations.
Keywords Cerebral metabolism - Hypoglycaemia counter-regulation - Insulin antagonists - Near-normoglycaemic insulin therapy - Phosphate compounds - Phosphorus-31 nuclear magnetic resonance spectroscopy - Type 1 diabetes mellitus