title: Brain glycogen content and metabolism in subjects with type 1 diabetes and hypoglycemia unawareness.
abstract: Supercompensated brain glycogen may contribute to the development of hypoglycemia unawareness in patients with type 1 diabetes by providing energy for the brain during periods of hypoglycemia. Our goal was to determine if brain glycogen content is elevated in patients with type 1 diabetes and hypoglycemia unawareness. We used in vivo (13)C nuclear magnetic resonance spectroscopy in conjunction with [1-(13)C]glucose administration in five patients with type 1 diabetes and hypoglycemia unawareness and five age-, gender-, and body mass index-matched healthy volunteers to measure brain glycogen content and metabolism. Glucose and insulin were administered intravenously over ∼51 hours at a rate titrated to maintain a blood glucose concentration of 7 mmol/L. (13)C-glycogen levels in the occipital lobe were measured at ∼5, 8, 13, 23, 32, 37, and 50 hours, during label wash-in and wash-out. Newly synthesized glycogen levels were higher in controls than in patients (P<0.0001) for matched average blood glucose and insulin levels, which may be due to higher brain glycogen content or faster turnover in controls. Metabolic modeling indicated lower brain glycogen content in patients than in controls (P=0.07), implying that glycogen supercompensation does not contribute to the development of hypoglycemia unawareness in humans with type 1 diabetes.
authors.affiliation: Department of Radiology, Center for Magnetic Resonance Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA. gulin@cmrr.umn.edu
authors.forename: Gülin
authors.initials: G
authors.lastname: Öz
authors.forename: Nolawit
authors.initials: N
authors.lastname: Tesfaye
authors.forename: Anjali
authors.initials: A
authors.lastname: Kumar
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Deelchand
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Eberly
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Seaquist
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen