Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency

Cigdem I. Akman, Kristin Engelstad, Veronica J. Hinton, Paivi Ullner, Dorcas Koenigsberger, Linda D Leary, Dong Wang, Darryl C. De Vivo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired micro-cephaly, 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.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalAnnals of Neurology
Volume67
Issue number1
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Glucose Transporter Type 1
Hyperglycemia
Glucose Tolerance Test
Seizures
Glucose
Homeostasis
Carbohydrates
Insulin
Haploinsufficiency
Dystonia
Brain
Physiologic Monitoring
Ataxia
Blood-Brain Barrier
Energy Metabolism
Serum
Glut1 Deficiency Syndrome

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Akman, C. I., Engelstad, K., Hinton, V. J., Ullner, P., Koenigsberger, D., Leary, L. D., ... De Vivo, D. C. (2010). Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency. Annals of Neurology, 67(1), 31-40. https://doi.org/10.1002/ana.21797

Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency. / Akman, Cigdem I.; Engelstad, Kristin; Hinton, Veronica J.; Ullner, Paivi; Koenigsberger, Dorcas; Leary, Linda D; Wang, Dong; De Vivo, Darryl C.

In: Annals of Neurology, Vol. 67, No. 1, 2010, p. 31-40.

Research output: Contribution to journalArticle

Akman, CI, Engelstad, K, Hinton, VJ, Ullner, P, Koenigsberger, D, Leary, LD, Wang, D & De Vivo, DC 2010, 'Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency', Annals of Neurology, vol. 67, no. 1, pp. 31-40. https://doi.org/10.1002/ana.21797
Akman CI, Engelstad K, Hinton VJ, Ullner P, Koenigsberger D, Leary LD et al. Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency. Annals of Neurology. 2010;67(1):31-40. https://doi.org/10.1002/ana.21797
Akman, Cigdem I. ; Engelstad, Kristin ; Hinton, Veronica J. ; Ullner, Paivi ; Koenigsberger, Dorcas ; Leary, Linda D ; Wang, Dong ; De Vivo, Darryl C. / Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency. In: Annals of Neurology. 2010 ; Vol. 67, No. 1. pp. 31-40.
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