Inflammatory profile of diabetic ketoacidosis in children with type 1 diabetes

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.