Increased Brain Lactate Concentrations Without Increased Lactate Oxidation During Hypoglycemia in Type 1 Diabetic Individuals
- Henk M. De Feyter1,
- Graeme F. Mason1,2,
- Gerald I. Shulman3,4,5,
- Douglas L. Rothman1,6 and
- Kitt Falk Petersen3⇑
- 1Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
- 2Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
- 3Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
- 4Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut
- 5Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut
- 6Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut
- Corresponding author: Kitt Falk Petersen, .
Previous studies have reported that brain metabolism of acetate is increased more than twofold during hypoglycemia in type 1 diabetic (T1D) subjects with hypoglycemia unawareness. These data support the hypothesis that upregulation of blood-brain barrier monocarboxylic acid (MCA) transport may contribute to the maintenance of brain energetics during hypoglycemia in subjects with hypoglycemia unawareness. Plasma lactate concentrations are ∼10-fold higher than acetate concentrations, making lactate the most likely alternative MCA as brain fuel. We therefore examined transport of [3-13C]lactate across the blood-brain barrier and its metabolism in the brains of T1D patients and nondiabetic control subjects during a hypoglycemic clamp using 13C magnetic resonance spectroscopy. Brain lactate concentrations were more than fivefold higher (P < 0.05) during hypoglycemia in the T1D subjects compared with the control subjects. Surprisingly, we observed no increase in the oxidation of blood-borne lactate in the T1D subjects, as reflected by similar 13C fractional enrichments in brain glutamate and glutamine. Taken together, these data suggest that in addition to increased MCA transport at the blood-brain barrier, there may be additional metabolic adaptations that contribute to hypoglycemia unawareness in patients with T1D.
- Received February 22, 2013.
- Accepted May 18, 2013.
- © 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.