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, M. G. F.; Ortiz, Luis A.; Mulder, Dries; Tjan, David H; Martin, Alvaro; Tatomir, Alexandru; Rus, Horea

doi:10.1016/j.yexmp.2017.05.013

Cited by 5 publications

(8 citation statements)

References 61 publications

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“…Interestingly, animal (rat) models of DKA also demonstrate a deficit in object location ( 28 ). As shown by Glaser et al ( 20 ) and Hoffman et al ( 29 ), the hippocampus is particularly vulnerable to ischemic/reperfusion of the brain. Recent immunohistochemistry findings show the presence of neuroinflammatory markers in the hippocampus of individuals who died of DKA with and without cerebral edema ( 29 ).…”

Section: Discussionmentioning

confidence: 92%

“…As shown by Glaser et al ( 20 ) and Hoffman et al ( 29 ), the hippocampus is particularly vulnerable to ischemic/reperfusion of the brain. Recent immunohistochemistry findings show the presence of neuroinflammatory markers in the hippocampus of individuals who died of DKA with and without cerebral edema ( 29 ). Therefore, it is notable that we found the moderate/severe group had lower memory performance scores compared with the none/mild group.…”

Section: Discussionmentioning

confidence: 92%

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Impact of Early Diabetic Ketoacidosis on the Developing Brain

et al. 2018

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OBJECTIVE This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes. RESEARCH DESIGN AND METHODS Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months. RESULTS In 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA 1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores and cognitive performance on the Detectability and Commission subtests of the Conners’ Continuous Performance Test II and the Dot Locations subtest of the Children’s Memory Scale. CONCLUSIONS A single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Impact of Early Diabetic Ketoacidosis on the Developing Brain

et al. 2018

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“…After 20 h of treatment, our patient developed increased drowsiness and irregular respiratory pattern, which implied the presence of CE and was a major cause of the aggravation of her condition. The underlying mechanisms of CE remain unknown, and previous studies revealed that increased utilization of ketone bodies of immature brains, the low levels of antioxidant defenses in the brain, a more severe systemic immune response and neuroinflammatory responses, the susceptibility of immature blood–brain barrier, and dysfunction of cerebrovascular endothelial cells may contribute to the pathogenesis [ 10 ]. Besides, DKA-induced inflammation will increase systemic inflammatory markers, including heat-shock proteins, complements, and pro-inflammatory cytokines IL1β, IL-2, IL-6, IL8, and TNF-α [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy

et al. 2018

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Neonatal diabetes mellitus (NDM) is a rare monogenic disorder presenting as uncontrolled hyperglycemia during the first 6 months of life. Hyperglycemic hyperosmolar state (HHS) is quite rare in NDM patients, and reported experience with this condition is limited. Continuous renal replacement therapy (CRRT) is frequently used as a mode of dialytic treatment in critically ill patients with acute renal failure, but has seldom been used in patients with diabetic ketoacidosis (DKA) and HHS. We report the case of a 2-month-old infant admitted to our hospital presenting with dyspnea and lethargy. Blood gas showed severe hyperosmotic DKA. After 21 h of fluid and insulin therapy, the baby presented with increased drowsiness and irregular respiration, which suggested cerebral edema. Moreover, the DKA and HHS were exacerbated. After 18 h of CRRT, the patient gradually recovered from DKA and HHS. The gene analysis revealed a de novo mutation (c.602G > A (p.R201H)) of the KCNJ11 gene, and oral glibenclamide successfully replaced insulin treatment in the patient.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0484-3) contains supplementary material, which is available to authorized users.

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“…Studies in both animal models 82‐85 and humans 86‐101 have also suggested that systemic and cerebrovascular inflammation are associated with the development of CE in DKA. Inflammatory processes are thought to contribute to vasogenic injury through their damaging effects on the BBB 102‐105 .…”

Section: Vasogenic Injurymentioning

confidence: 99%

“…• Increased neuronal expression of cytokines, adhesion molecules, complement peptides, 95‐97 ROS, 98‐100 and receptor for AGEs 101 …”

Section: Vasogenic Injurymentioning

confidence: 99%

Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema

2020

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Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia–reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contributing to its pathogenesis. The role of specific aspects of DKA treatment in the development of CE continues to be controversial. This review critically examines the literature on the pathophysiology of CE and attempts to categorize the findings by types of brain injury that contribute to its development: cytotoxic, vasogenic, and osmotic. Utilizing this scheme, we propose a multifactorial pathway for the development of CE in patients with DKA.

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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?

Cited by 5 publications

References 61 publications

Impact of Early Diabetic Ketoacidosis on the Developing Brain

Impact of Early Diabetic Ketoacidosis on the Developing Brain

Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy

Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema

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