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Diabetic Ketoacidosis and The Developing Brain

Mar 19, 2019
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy

Single episode of moderate/severe DKA in young children at diagnosis associated with lower cognitive scores, altered brain growth.

Diabetic ketoacidosis disrupts memory function, underscoring the importance of diabetic ketoacidosis prevention when type 1 diabetes mellitus (T1DM) is known, and of prompt diagnosis of children with new onset of T1DM, according to a study by S. Ghetti et al. Thirty-three children with type 1 diabetes mellitus (T1DM) and a history of DKA and 29 children with T1DM without a history of DKA were enrolled from the pediatric endocrinology clinic at the University of California, Davis, Medical Center. These groups were comparable on demographic and disease-related variables. These groups’ ability to recall events in association with specific details, the memory function most directly affected by mild hypoxia/ischemia, was compared on two tasks (event-color associations and event-spatial position associations).

In multivariate analyses controlling for other critical variables, children with DKA history had significantly lower rates of accurate memory on both tasks than did children without DKA history.

Cerebral edema associated with severe disturbances in neurological function and high mortality rates has long been recognized as a rare but serious complication of DKA in children. Subtle cerebral injury may occur in the majority of children with DKA, even among those with minimal or no alterations in mental status.

Studies using magnetic resonance imaging in children and in an animal model demonstrated changes in cerebral water distribution, blood flow, and metabolism during DKA similar to those often observed in hypoxic/ischemic cerebral injury.

A recent study, published in Diabetes Care in March 2019, aimed to determine how the severity of a DKA episode is associated with longitudinal memory and brain changes in young children with type 1 diabetes.

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.

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 HbA1c 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.

The study concluded that even a single episode of moderate/severe DKA in very young children with type 1 diabetes is associated with lower cognitive scores and altered brain growth. The results suggest that recognition of the immediate and longitudinal effect of a history of DKA on the brain further supports the development of programs to screen family members when there is an increased risk of type 1 diabetes to increase awareness of symptoms of type 1 diabetes, reduce the occurrence of DKA at diagnosis, and develop a closed-loop control or islet replacement to prevent further episodes of DKA after diagnosis.

Practice Pearls:

  • Recent studies have demonstrated that even a single episode of diabetic ketoacidosis in young children with type 1 diabetes is associated with lower cognitive scores and altered brain growth.
  • Studies with larger sample sizes and studies at the time of diagnosis to assess the acute effect of diabetic ketoacidosis are needed.
  • Further studies are also 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.

References:

Aye T, Mazaika PK, Mauras N, Marzelli MJ, Shen H, Hershey T, Cato A, Weinzimer SA, White NH, Tsalikian E, Jo B, Reiss AL; Diabetes Research in Children Network (DirecNet) Study Group. Impact of Early Diabetic Ketoacidosis on the Developing Brain. Diabetes Care. 2019 Mar;42(3):443-449.

Ghetti S, Lee JK, Sims CE, Demaster DM, Glaser NS. Diabetic ketoacidosis and memory dysfunction in children with type 1 diabetes. J Pediatr. 2010 Jan;156(1):109-14.

Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy