Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism

Diabetes. 2012 Jul;61(7):1831-7. doi: 10.2337/db11-1286. Epub 2012 Apr 12.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / analysis
  • Adenosine Triphosphate / metabolism
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Aspartic Acid / metabolism
  • Brain Edema / etiology
  • Brain Edema / metabolism
  • Brain Edema / physiopathology
  • Cerebrum / blood supply
  • Cerebrum / metabolism
  • Cerebrum / physiopathology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Ketoacidosis / complications
  • Diabetic Ketoacidosis / metabolism
  • Diabetic Ketoacidosis / physiopathology*
  • Diet, High-Fat / adverse effects
  • Hyperglycemia / metabolism
  • Hyperglycemia / physiopathology*
  • Lactic Acid / analysis
  • Lactic Acid / metabolism
  • Magnetic Resonance Spectroscopy
  • Phosphates / analysis
  • Phosphates / metabolism
  • Phosphocreatine / analysis
  • Phosphocreatine / metabolism
  • Rats
  • Water / analysis
  • Water / metabolism

Substances

  • Phosphates
  • Phosphocreatine
  • Water
  • Aspartic Acid
  • Lactic Acid
  • Adenosine Triphosphate
  • N-acetylaspartate