Markers of immune-mediated inflammation in the brains of young adults and adolescents with type 1 diabetes and fatal diabetic ketoacidosis. Is there a difference?

Exp Mol Pathol. 2017 Jun;102(3):505-514. doi: 10.1016/j.yexmp.2017.05.013. Epub 2017 May 19.

Abstract

Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0.03). CD59, a MAC assembly inhibitory protein was absent, possibly suppressed by the hyperglycemia in the teenagers but was expressed in the young adults despite comparable average levels of hyperglycemia. The receptor for advanced glycation end products (RAGE) had an average expression in the young adults significantly greater than in the teenagers (p=0.02). The autophagy marker Light Chain 3 (LC3) A/B was the predominant form of programmed cell death (PCD) in the teenage brains. The young adults had high expressions of both LC3A/B and TUNEL, an apoptotic cell marker for DNA fragmentation. BE was present in the newly diagnosed young adult with hyperglycemic hyperosmolar DKA and also in the two teenagers. Our data indicate that significant differences in neuroinflammatory components, initiated by the dysregulation of DKA and interrelated metabolic and immunologic milieu, are likely present in the brains of fatal DKA of teenagers when compared with young adults.

Keywords: Brain edema; C5b-9; Diabetic ketoacidosis; Neuroinflammation; Receptor for advanced glycation end products; Type 1 diabetes.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Autophagy
  • Biomarkers / metabolism*
  • Brain / physiopathology
  • Brain Edema / diagnosis
  • Brain Edema / etiology
  • Brain Edema / genetics
  • CD59 Antigens / genetics
  • CD59 Antigens / metabolism
  • DNA Fragmentation
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetic Ketoacidosis / complications
  • Diabetic Ketoacidosis / genetics*
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inflammation Mediators / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Neurogenic Inflammation / etiology
  • Neurogenic Inflammation / genetics*
  • Young Adult

Substances

  • Biomarkers
  • CD59 Antigens
  • Inflammation Mediators
  • Microtubule-Associated Proteins
  • light chain 3, human
  • CD59 protein, human