title: Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.
abstract: Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, Davis, Sacramento, California, USA. nsglaser@ucdavis.edu
authors.forename: Nicole
authors.initials: N
authors.lastname: Glaser
authors.forename: Catherine
authors.initials: C
authors.lastname: Ngo
authors.forename: Steven
authors.initials: S
authors.lastname: Anderson
authors.forename: Natalie
authors.initials: N
authors.lastname: Yuen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trifu
authors.forename: Martha
authors.initials: M
authors.lastname: O'Donnell
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D054022:Cerebrum / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D016883:Diabetic Ketoacidosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D019344:Lactic Acid / Q000032:analysis / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000032:analysis / Q000378:metabolism; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D014867:Water / Q000032:analysis / Q000378:metabolism
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; D014867:Water; D001224:Aspartic Acid; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate