title: Circulating matrix metalloproteinases in children with diabetic ketoacidosis.
abstract: 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.
  
  
  
  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 2 h of beginning intravenous fluids) and during therapy (time 2; median 8 h; range: 4-16 h). 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.
  
  
  
  In children with DKA compared with diabetes controls, circulating MMP-2 levels were lower (mean 77 vs. 244 ng/mL, p < 0.001), MMP-3 levels were similar (mean 5 vs. 4 ng/mL, p = 0.57), and MMP-9 levels were higher (mean 67 vs. 25 ng/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).
  
  
  
  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.
authors: Departments of Pediatrics and Emergency Medicine, Rhode Island Hospital, Providence, RI, USA.|Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors: Aris
authors: A
authors: Garro
authors: Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors: Adam
authors: A
authors: Chodobski
authors: Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors: Joanna
authors: J
authors: Szmydynger-Chodobska
authors: Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors: Rongzi
authors: R
authors: Shan
authors: Departments of Pediatrics and Emergency Medicine, Rhode Island Hospital, Providence, RI, USA.|Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors: Shara R
authors: SR
authors: Bialo
authors: Department of Pediatrics, Sidney Kimmel Medical College at Thomas Jefferson University, Wilmington, DE, USA.
authors: Jonathan
authors: J
authors: Bennett
authors: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
authors: Kimberly
authors: K
authors: Quayle
authors: Department of Pediatrics, University of Colorado, School of Medicine, Denver, CO, USA.
authors: Arleta
authors: A
authors: Rewers
authors: Department of Pediatrics, University of Utah, School of Medicine, Salt Lake City, UT, USA.
authors: Jeffrey E
authors: JE
authors: Schunk
authors: Department of Pediatrics, University of Utah, School of Medicine, Salt Lake City, UT, USA.
authors: T Charles
authors: TC
authors: Casper
authors: Department of Emergency Medicine, University of California Davis, Davis, CA, USA.
authors: Nathan
authors: N
authors: Kuppermann
authors: Department of Pediatrics, University of California Davis, Davis, CA, USA.
authors: Nicole
authors: N
authors: Glaser
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000628:therapy; D016883:Diabetic Ketoacidosis / Q000097:blood* / Q000628:therapy; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D006442:Glycated Hemoglobin; D020782:Matrix Metalloproteinases
keywords: biomarkers; cerebral edema; cerebral injury; type 1 diabetes mellitus