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Updated: Mar 26, 2026
Detection of Functional Matrix Metalloproteinases by Zymography
Published on: November 8, 2010
Circulating matrix metalloproteinases in children with diabetic ketoacidosis
Aris Garro1,2, Adam Chodobski2, Joanna Szmydynger-Chodobska2
1Departments of Pediatrics and Emergency Medicine, Rhode Island Hospital, Providence, RI, USA.
Insights
Children with diabetic ketoacidosis (DKA) show lower matrix metalloproteinase-2 (MMP-2) and higher MMP-9 levels compared to those with type 1 diabetes. These MMP alterations may contribute to blood-brain barrier dysfunction in DKA.
Area of Science:
- Biochemistry
- Endocrinology
- Neurology
Background:
- Matrix metalloproteinases (MMPs) are implicated in blood-brain barrier (BBB) dysfunction during inflammatory conditions.
- Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus (T1DM) that can lead to neurological complications.
- Understanding MMP involvement in DKA is crucial for managing potential BBB disturbances.
Purpose of the Study:
- To compare circulating levels of MMP-2, MMP-3, and MMP-9 in children with DKA versus children with T1DM without DKA.
- To investigate the correlation between MMP levels and DKA severity markers.
Main Methods:
- A prospective study involving 34 children with DKA and 23 controls with T1DM without DKA.
- Plasma MMP-2, MMP-3, and MMP-9 levels were measured early during DKA treatment and during therapy.
- Correlations with clinical parameters like pH, bicarbonate, and hemoglobin A1c were analyzed.
Main Results:
- Children with DKA exhibited significantly lower MMP-2 levels (77 vs. 244 ng/mL) and higher MMP-9 levels (67 vs. 25 ng/mL) compared to controls.
- MMP-3 levels were similar between the groups.
- MMP-2 levels correlated with pH and serum bicarbonate, while MMP-9 levels correlated with hemoglobin A1c and remained elevated in DKA.
Conclusions:
- Circulating MMP-2 and MMP-9 levels are altered in children experiencing DKA.
- Elevated MMP-9 and reduced MMP-2 in DKA may play a role in mediating BBB dysfunction.
- Further research is warranted to elucidate the precise mechanisms of MMPs in DKA-associated neurological complications.
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.
