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Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency
Author(s) -
Akman Cigdem I.,
Engelstad Kristin,
Hinton Veronica J.,
Ullner Paivi,
Koenigsberger Dorcas,
Leary Linda,
Wang Dong,
De Vivo Darryl C.
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21797
Subject(s) - transient (computer programming) , medicine , glucose transporter , transporter , endocrinology , insulin , chemistry , gene , biochemistry , computer science , operating system
Objective Glucose transporter type 1 deficiency syndrome (Glut1‐DS) is characterized clinically by acquired microcephaly, infantile‐onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5‐hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain. Methods Thirteen Glut1‐DS patients completed a 5‐hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well‐being. All patients had a full neuropsychological battery prior to OGTT. Results The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well‐being were observed without any change in memory performance. Interpretation This study documents transient neurological improvement in Glut1‐DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood‐brain barrier. The transient improvement in brain function underscores the rate‐limiting role of glucose transport and the critical minute‐to‐minute dependence of cerebral function on fuel availability for energy metabolism. ANN NEUROL 2010;67:31–40