title: Brain Lactate Concentration Falls in Response to Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.
abstract: Brain lactate may be involved in the development of impaired awareness of hypoglycemia (IAH), a condition that affects approximately 25% of patients with type 1 diabetes and increases the risk of severe hypoglycemia. The aim of this study was to investigate the effect of acute hypoglycemia on brain lactate concentration in patients with IAH as compared with those with normal awareness of hypoglycemia (NAH) and healthy control subjects (n = 7 per group). After an overnight fast, all subjects underwent a two-step hyperinsulinemic euglycemic (5.0 mmol/L)-hypoglycemic (2.8 mmol/L) glucose clamp. Brain lactate concentrations were measured continuously with (1)H-MRS using a specific lactate detection method. Hypoglycemia generated symptoms in patients with NAH and healthy control subjects but not in patients with IAH. Brain lactate fell significantly by ∼20% in response to hypoglycemia in patients with type 1 diabetes with IAH but remained stable in both healthy control subjects and in patients with NAH. The fall in brain lactate is compatible with increased brain lactate oxidation providing an alternative fuel source during hypoglycemia, which may contribute to the impaired detection of hypoglycemia.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, the Netherlands evita.wiegers@radboudumc.nl.
authors.forename: Evita C
authors.initials: EC
authors.lastname: Wiegers
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Rooijackers
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Bastiaan E
authors.initials: BE
authors.lastname: de Galan
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, the Netherlands 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 / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055815:Young Adult
chemical_list: D007328:Insulin; D019344:Lactic Acid