TY - JOUR
T1 - Circulating matrix metalloproteinases in children with diabetic ketoacidosis
AU - for the Pediatric Emergency Care Applied Research Network (PECARN)
AU - Garro, Aris
AU - Chodobski, Adam
AU - Szmydynger-Chodobska, Joanna
AU - Shan, Rongzi
AU - Bialo, Shara R.
AU - Bennett, Jonathan
AU - Quayle, Kimberly
AU - Rewers, Arleta
AU - Schunk, Jeffrey E.
AU - Casper, T. Charles
AU - Kuppermann, Nathan
AU - Glaser, Nicole
N1 - Funding Information:
This study was supported by grant 1R01HD062417-01 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and by basic science grant 7-12-BS-060 from the American Diabetes Association. This project was also supported in part by the Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB), Emergency Medical Services for Children (EMSC) Network Development Demonstration Program under cooperative agreements U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685. The information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government. We thank the PECARN Research Coordinators and clinicians around the PECARN Network who are enrolling children into this study. We also thank Julie Sarri for technical assistance in processing blood samples and assisting ELISA.
Publisher Copyright:
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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 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. Results: 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). 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.
AB - 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 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. Results: 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). 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.
KW - biomarkers
KW - cerebral edema
KW - cerebral injury
KW - type 1 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=84959310875&partnerID=8YFLogxK
U2 - 10.1111/pedi.12359
DO - 10.1111/pedi.12359
M3 - Article
C2 - 26843101
AN - SCOPUS:84959310875
VL - 18
SP - 95
EP - 102
JO - Pediatric Diabetes
JF - Pediatric Diabetes
SN - 1399-543X
IS - 2
ER -