Z. Chaffin, S. Ghetti, D. Tancredi, A. Rewers, M. Rewers, S. Gilles, B. Ander, et al. (2026). Inflammatory profile of diabetic ketoacidosis in children with type 1 diabetes. BMJ open diabetes research & care, 14(2). https://doi.org/10.1136/bmjdrc-2025-004961

PubMed 41807017

[Abstract]
INTRODUCTION: Diabetic ketoacidosis (DKA) occurs frequently in children with type 1 diabetes (T1D). The inflammatory response to DKA may play a role in complications, but the inflammatory pattern is not well characterized. We aimed to describe the inflammatory profile during and after DKA.

RESEARCH DESIGN AND METHODS: We evaluated inflammatory mediators (cytokines, chemokines, growth factors, and matrix metalloproteinases) using multiplex immunoassays in children (1) hospitalized with acute DKA (6-8 hours after beginning treatment, (n=15), (2) seen in the outpatient diabetes clinic 2-5 days after DKA (n=14), (3) hospitalized with new-onset T1D without DKA <24 hours after beginning insulin (n=9), and (4) referred to the outpatient diabetes clinic for new-onset T1D without DKA 2-5 days after beginning insulin (n=14). Children with chronic T1D and glycated hemoglobin <8.0% (n=59) undergoing routine phlebotomy served as a reference group.

RESULTS: Compared with the reference group, children with acute DKA had significant alterations in interleukin 1 (IL-1) receptor antagonist (IL-1RA), IL-6, IL-8, IL-10, IL-18, chemokine C-X-C motif ligand (CXCL) 5, CXCL10, chemokine C-C motif ligand (CCL) 27, tumor necrosis factor-related apoptosis-inducing ligand, granulocyte colony-stimulating factor, tissue inhibitor of metalloproteinase 2 (TIMP-2), TIMP-4, matrix metalloproteinase 2 (MMP-2), MMP-3, MMP-7, MMP-9, and MMP-10. MMP-3, MMP-10, TIMP-1, and IL-1RA were also elevated 2-5 days after DKA (false discovery rate-adjusted p<0.10 for all). MMP-2 and MMP-9 levels were altered in children with new-onset T1D without DKA <24 hours after starting insulin, but no significant inflammatory changes were found in new-onset T1D 2-5 days after starting insulin.

CONCLUSIONS: DKA causes a unique inflammatory pattern distinct from inflammatory changes in acute hyperglycemia or T1D-related autoimmunity. Alterations in MMPs and their tissue inhibitors play a dominant role in this inflammatory profile.