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?

William H. Hoffman, Carol M. Artlett, Dallas Boodhoo, Mary G.F. Gilliland, Luis A Ortiz, Dries Mulder, David H.T. Tjan, Alvaro Martin, Alexandru Tatomir, Horea Rus

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalExperimental and Molecular Pathology
Volume102
Issue number3
DOIs
StatePublished - Jun 1 2017

Fingerprint

Diabetic Ketoacidosis
Encephalitis
Medical problems
Complement Membrane Attack Complex
Type 1 Diabetes Mellitus
Young Adult
Brain
Biomarkers
Hyperglycemia
Cell death
Deposits
Cells
Brain Edema
Autophagy
In Situ Nick-End Labeling
DNA Fragmentation
DNA
Cell Death
Immunohistochemistry
Proteins

Keywords

  • Brain edema
  • C5b-9
  • Diabetic ketoacidosis
  • Neuroinflammation
  • Receptor for advanced glycation end products
  • Type 1 diabetes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

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? / Hoffman, William H.; Artlett, Carol M.; Boodhoo, Dallas; Gilliland, Mary G.F.; Ortiz, Luis A; Mulder, Dries; Tjan, David H.T.; Martin, Alvaro; Tatomir, Alexandru; Rus, Horea.

In: Experimental and Molecular Pathology, Vol. 102, No. 3, 01.06.2017, p. 505-514.

Research output: Contribution to journalArticle

Hoffman, William H. ; Artlett, Carol M. ; Boodhoo, Dallas ; Gilliland, Mary G.F. ; Ortiz, Luis A ; Mulder, Dries ; Tjan, David H.T. ; Martin, Alvaro ; Tatomir, Alexandru ; Rus, Horea. / 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?. In: Experimental and Molecular Pathology. 2017 ; Vol. 102, No. 3. pp. 505-514.
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