Brain energy metabolism during hypoglycaemia in healthy and Type 1 diabetic subjects

• Published in: Diabetologia Vol. 47; no. 4; pp. 648 - 651
• Main Authors: BISCHOF, M. G, MLYNARIK, V, BREHM, A, BERNROIDER, E, KRSSAK, M, BAUER, E, MADL, C, BAYERLE-EDER, M, WALDHÄUSL, W, RODEN, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.04.2004; Springer Nature B.V
• Subjects: Adenosine Triphosphate - metabolism; Adult; Biological and medical sciences; Blood Glucose - metabolism; Brain Chemistry - physiology; Diabetes Mellitus, Type 1 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism - physiology; Glucose Clamp Technique; Hormones - blood; Humans; Hypoglycemia - metabolism; Magnetic Resonance Spectroscopy; Male; Medical sciences; Phosphocreatine - metabolism; Endocrinopathy; Human; Insulin antagonists; Pancreatic hormone; Energy metabolism; Cerebral metabolism; Central nervous system; Hypoglycaemia counter-regulation; Metabolic diseases; Phosphorus; NMR spectrometry; Hypoglycemia; Insulin; Phosphate compounds; Encephalon; Type 1 diabetes; Near-normoglycaemic insulin therapy; Antagonist; Phosphorus-31 nuclear magnetic resonance spectroscopy; Type 1 diabetes mellitus
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-004-1362-2

This study aimed to examine brain energy metabolism during moderate insulin-induced hypoglycaemia in Type 1 diabetic patients and healthy volunteers. 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 (approximately 3.0 mmol/l) hyperinsulinaemic (1.5 mU x 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). During hypoglycaemia, the diabetic patients showed blunted endocrine counter-regulation. Throughout the study, the phosphocreatine:gamma-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 micromol/l; p<0.05). Despite a lower cerebral phosphocreatine:gamma-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.