Extracellular(Serum) Levels of Matrix Metalloproteinases in Pediatric Type 1 Diabetes Mellitus and Association with Diabetic Ketoacidosis and Cerebral Edema

Qingbo Xu,1,2 Yu Yang,1,2 Qiang Huang,1– 3 Liling Xie,1,2 Yaqin Feng,1,2 Li Yang1,2 1Department of Endocrinology, Jiangxi Provincial Children’s Hospital, Nanchang, Jiangxi, 330038, People’s Republic of China; 2The Affiliated Children’s Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330038, People’s Republic of China; 3Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Li Yang, Email [email protected]: Type 1 diabetes mellitus (T1DM) in children is associated with acute complications such as diabetic ketoacidosis (DKA) and the severe risk of diabetic ketoacidosis-related cerebral edema (DKACE). Matrix metalloproteinases (MMPs) are implicated in inflammation and tissue remodeling, potentially contributing to these complications. This study explores the role of MMPs as biomarkers in pediatric T1DM patients with DKA and DKACE.Methods: We conducted a systematic cross-sectional study at Jiangxi Children’s Hospital, enrolling 56 pediatric patients with T1DM, categorized into three groups: T1DM without complications, DKA, and DKACE. Serum levels of MMP-2, MMP-3, and MMP-9 were measured through ELISA. Statistical analyses assessed correlations between MMPs, glucose metabolism, and inflammatory markers, evaluating potential biomarker utility in disease characterization.Results: MMP-3 and MMP-9 levels were significantly elevated in the DKACE group compared to the T1DM and DKA groups, exhibiting strong correlations with decreased pH and bicarbonate levels (both p < 0.001). MMP-2 levels were reduced in DKACE, correlating positively with pH and bicarbonate levels. Post-clinical improvement analyses demonstrated no significant differences in MMP levels between DKA and DKACE groups, suggesting stabilization post-treatment regardless of initial acidosis severity.Conclusion: The distinct patterns of MMP-3 and MMP-9 elevations in DKACE highlight their potential as biomarkers for identifying and monitoring severe DKA complications. The findings suggest these enzymes play a significant role in cerebral edema pathophysiology, making them viable targets for future therapeutic interventions. Keywords: pediatric diabetic ketoacidosis, cerebral edema, matrix metalloproteinases, type 1 diabetes mellitus