Diabetic Ketoacidosis Alters Plasma Levels of Matrix Metalloproteinases and PMN‐Specific Elastase in Children

Abstract

IntroductionDiabetic ketoacidosis (DKA) is associated with cerebrovascular complications in children such as vasogenic edema. Circulating matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and other proteases may contribute to loss of cerebrovascular endothelial cell junctional integrity. Our aim was to determine the effects of acute DKA on systemic MMP/TIMP levels, as well as polymorphonuclear neutrophil(PMN)‐specific elastase.MethodsPlasma was obtained from children ages 4‐17 years old, with type‐1 diabetes, either in an acute DKA state or insulin‐controlled (CON). DKA and CON samples were age‐ and sex‐matched for all experiments. Gelatin zymography was used to assess gelatinolytic activity. ELISA‐based methods were used to assess plasma concentration of proteins.ResultsDKA plasma showed significantly increased MMP‐9 activity(P<0.01) and decreased MMP‐2 activity(P<0.001), compared to CON plasma. MMP‐9 activity in DKA plasma was inversely correlated with pH(P<0.05). DKA plasma had increased circulating levels of MMP‐3(P<0.05), MMP‐8(P<0.001) and TIMP‐4(P<0.01). In addition, a significant increase in circulating levels of PMN elastase(P<0.001) was detected in DKA plasma.SummaryDKA is associated with dynamic changes in plasma levels of MMP‐2, MMP‐3, MMP‐8, MMP‐9 and TIMP‐4, as well as PMN elastase, which may contribute to loss of blood‐brain barrier integrity.