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

Nicole Glaser, Catherine Ngo, Steven Anderson, Natalie Yuen, Alexandra Trifu, Martha O'Donnell, Nicole Glaser, Catherine Ngo, Steven Anderson, Natalie Yuen, Alexandra Trifu, Martha O'Donnell

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.

Figures

FIG. 1.
FIG. 1.
A: CBF in hyperglycemic and ketotic rats in comparison with control rats measured using arterial spin labeling (means ± SE for 10 ketotic, 10 control, and 9 hyperglycemic rats). Cortex: P = 0.03 hyperglycemic vs. control, P = 0.02 ketotic vs. control. Striatum: P = 0.06 hyperglycemic vs. control, P = 0.07 ketotic vs. control. B: Apparent diffusion coefficients in hyperglycemic rats and ketotic rats in comparison with control rats (means ± SE for 10 ketotic and 10 control rats and 9 hyperglycemic rats). Cortex: P = 0.004 hyperglycemic vs. control, P = 0.012 ketotic vs. control. Striatum: P = 0.019 hyperglycemic vs. control, P = 0.46 ketotic vs. control.
FIG. 2.
FIG. 2.
Cerebral metabolites in hyperglycemic rats and ketotic rats in comparison with control rats measured using proton and phosphorus MRS (means ± SE; n = 7 for all groups). A: PCr-to-Pi ratio. B: ATP-to-Pi ratio. C: Intracellular (Int) pH. D: Lactate (Lac)-to-Cr ratio. E: NAA-to-Cr ratio.

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