Patients with type 1 diabetes exhibit altered cerebral metabolism during hypoglycemia

• Published in: The Journal of clinical investigation Vol. 123; no. 2; pp. 623 - 629
• Main Authors: van de Ven, Kim C C, Tack, Cees J, Heerschap, Arend, van der Graaf, Marinette, de Galan, Bastiaan E
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.02.2013
• Subjects: Adult; Biomedical research; Blood Glucose - metabolism; Brain; Brain - metabolism; Carbon Isotopes; Citric Acid Cycle; Complications and side effects; Development and progression; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Female; Genetic aspects; Glucagon; Glucose; Glucose Clamp Technique; Glucose metabolism; Glutamic Acid - metabolism; Glycated Hemoglobin - metabolism; Growth hormones; Humans; Hypoglycemia; Hypoglycemia - blood; Hypoglycemia - metabolism; Magnetic Resonance Spectroscopy; Male; Metabolism; Metabolites; Models, Biological; Physiological aspects; Plasma; Spectrum analysis; Type 1 diabetes; Young Adult; Netherlands
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI62742

Patients with type 1 diabetes mellitus (T1DM) experience, on average, 2 to 3 hypoglycemic episodes per week. This study investigated the effect of hypoglycemia on cerebral glucose metabolism in patients with uncomplicated T1DM. For this purpose, hyperinsulinemic euglycemic and hypoglycemic glucose clamps were performed on separate days, using [1-13C]glucose infusion to increase plasma 13C enrichment. In vivo brain 13C magnetic resonance spectroscopy was used to measure the time course of 13C label incorporation into different metabolites and to calculate the tricarboxylic acid cycle flux (VTCA) by a one-compartment metabolic model. We found that cerebral glucose metabolism, as reflected by the VTCA, was not significantly different comparing euglycemic and hypoglycemic conditions in patients with T1DM. However, the VTCA was inversely related to the HbA1C and was, under hypoglycemic conditions, approximately 45% higher than that in a previously investigated group of healthy subjects. These data suggest that the brains of patients with T1DM are better able to endure moderate hypoglycemia than those of subjects without diabetes.