Cerebral metabolic alterations in rats with diabetic ketoacidosis: Effects of treatment with insulin and intravenous fluids and effects of bumetanide

Nicole Glaser, Natalie Yuen, Steven E. Anderson, Daniel J Tancredi, Martha E O'Donnell

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

OBJECTIVE - Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND METHODS - We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 x 2 factorial study design. RESULTS - Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference -0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (-0.32 ± 0.10, P = 0.003, and -0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. CONCLUSIONS - These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment - consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline.

Original languageEnglish (US)
Pages (from-to)702-709
Number of pages8
JournalDiabetes
Volume59
Issue number3
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Cerebral metabolic alterations in rats with diabetic ketoacidosis: Effects of treatment with insulin and intravenous fluids and effects of bumetanide'. Together they form a unique fingerprint.

  • Cite this