title: Biomarkers and genetics of brain injury risk in diabetic ketoacidosis: A pilot study.
abstract: Diabetic ketoacidosis (DKA) is the primary cause of death for children with diabetes, especially when complicated by cerebral edema. Central nervous system (CNS) involvement is common, however the mechanism of, and predictors of CNS dysfunction/injury are largely unknown. In this observational pilot study, blood was collected from pediatric DKA patients at three time points (consent, 12 hr and 24 hr after beginning treatment), to test genetic markers, ribonucleic acid expression and plasma biomarkers reflecting inflammation (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and cerebral dysfunction and/or possible injury (S100β, glial fibrillary acidic protein [GFAP]). Thirty patients were enrolled in the study. The average age was 11.3 yr, 73% were new onset diabetes and 53% were female. Forty percent exhibited abnormal mentation (Glasgow Coma Scale <15), consistent with CNS dysfunction. IL-6 and TNF-α were elevated in plasma, suggesting systemic inflammation. GFAP was measurable in 45% of patients and correlated positively with GCS. Only two patients had detectable levels of S100β. In conclusion, children with DKA often present with evidence of acute neurologic dysfunction or injury. We have demonstrated the feasibility of exploring genetic and biochemical markers of potential importance in the pathophysiology of CNS dysfunction and/or possible injury in DKA. We have identified IL-6, TNF-α and GFAP as potentially important markers for further exploration. A larger, follow-up study will help to better understand the extent and type of CNS injury in DKA as well as the mechanism underlying this dysfunction/injury.
authors.affiliation: Department of Pediatric Critical Care Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA.
authors.forename: Sholeen T
authors.initials: ST
authors.lastname: Nett
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
authors.affiliation: Department of Pediatric Critical Care Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Levin
authors.affiliation: Department of Pediatric Critical Care Medicine, Children's Hospital and Research Center Oakland, Oakland, CA, USA.
authors.forename: Natalie Z
authors.initials: NZ
authors.lastname: Cvijanovich
authors.affiliation: Department of Pediatric Critical Care Medicine, University of Washington Children's Hospital, Seattle, WA, USA.
authors.forename: Monica S
authors.initials: MS
authors.lastname: Vavilala
authors.affiliation: Department of Pediatric Critical Care Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA.
authors.forename: J Dean
authors.initials: JD
authors.lastname: Jarvis
authors.affiliation: Department of Pediatric Critical Care Medicine, Children's Hospital and Research Center Oakland, Oakland, CA, USA.
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Flori
keywords: Cerebral edema; diabetic ketoacidosis; genetic biomarkers; pilot; vanguard