title: Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia.
abstract: It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.
authors.affiliation: 1 Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Evita C
authors.initials: EC
authors.lastname: Wiegers
authors.affiliation: 1 Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Becker
authors.affiliation: 2 Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Rooijackers
authors.affiliation: 3 Fraunhofer MEVIS, Institute for Medical Image Computing, Bremen, Germany.|4 Faculty of Physics and Electronics, University of Bremen, Bremen, Germany.
authors.forename: Federico C
authors.initials: FC
authors.lastname: von Samson-Himmelstjerna
authors.affiliation: 2 Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.affiliation: 1 Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: 2 Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Bastiaan E
authors.initials: BE
authors.lastname: de Galan
authors.affiliation: 1 Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|5 Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Marinette
authors.initials: M
authors.lastname: van der Graaf
mesh_terms: D000328:Adult; D001364:Awareness; D001783:Blood Flow Velocity / Q000502:physiology; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male
chemical_list: D007328:Insulin
keywords: Arterial spin labeling; cerebral blood flow; diabetes; hypoglycemia; magnetic resonance imaging