Circulating matrix metalloproteinases in children with diabetic ketoacidosis

Aris Garro, Adam Chodobski, Joanna Szmydynger-Chodobska, Rongzi Shan, Shara Bialo, Jonathan Bennett, Kimberly Quayle, Arleta Rewers, Jeffrey E. Schunk, T. Charles Casper, Nathan Kuppermann, Nicole Glaser

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10 Scopus citations

Abstract

Background and objective: Matrix metalloproteinases (MMPs) mediate blood-brain barrier dysfunction in inflammatory disease states. Our objective was to compare circulating MMPs in children with diabetic ketoacidosis (DKA) to children with type 1 diabetes mellitus without DKA. Research design and methods: This was a prospective study performed at five tertiary-care pediatric hospitals. We measured plasma MMP-2, MMP-3, and MMP-9 early during DKA (time 1; within 2h of beginning intravenous fluids) and during therapy (time 2; median 8 h; range: 4-16h). The primary outcome was MMP levels in 34 children with DKA vs. 23 children with type 1 diabetes without DKA. Secondary outcomes included correlations between MMPs and measures of DKA severity. Results: In children with DKA compared with diabetes controls, circulating MMP-2 levels were lower (mean 77 vs. 244ng/mL, p<0.001), MMP-3 levels were similar (mean 5 vs. 4ng/mL, p=0.57), and MMP-9 levels were higher (mean 67 vs. 25ng/mL, p=0.002) early in DKA treatment. MMP-2 levels were correlated with pH at time 1 (r=0.45, p=0.018) and time 2 (r=0.47, p=0.015) and with initial serum bicarbonate at time 2 (r=0.5, p=0.008). MMP-9 levels correlated with hemoglobin A1c in DKA and diabetes controls, but remained significantly elevated in DKA after controlling for hemoglobin A1c (β=-31.3, p=0.04). Conclusions: Circulating MMP-2 levels are lower and MMP-9 levels are higher in children during DKA compared with levels in children with diabetes without DKA. Alterations in MMP expression could mediate BBB dysfunction occurring during DKA.

Original languageEnglish (US)
JournalPediatric Diabetes
DOIs
StateAccepted/In press - 2016

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Keywords

  • Biomarkers
  • Cerebral edema
  • Cerebral injury
  • Type 1 diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

Cite this

Garro, A., Chodobski, A., Szmydynger-Chodobska, J., Shan, R., Bialo, S., Bennett, J., Quayle, K., Rewers, A., Schunk, J. E., Casper, T. C., Kuppermann, N., & Glaser, N. (Accepted/In press). Circulating matrix metalloproteinases in children with diabetic ketoacidosis. Pediatric Diabetes. https://doi.org/10.1111/pedi.12359