DKA Leads to Changes in Children’s Cognitive Function

Just one incident of DKA could potentially damage memory in children with type 1 diabetes. 

As we know, diabetic ketoacidosis (DKA) is a frequent complication in patients diagnosed with type 1 diabetes, and children who are recently diagnosed with type 1 diabetes often present with DKA. Although rare, damage to brain function is a severe outcome that can occur from a patient experiencing a DKA episode. The latest studies propose that brain injury can arise in children with no apparent neurological symptoms. For example, in a previous relevant study, the width of the frontal horns of a patients’ lateral ventricles in children with DKA during treatment and after recovery from the DKA episode was explored using magnetic resonance imaging. Narrowing of the lateral ventricles was present in more than half of the children treated for their DKA episodes. Some reports link DKA and cognitive changes such as memory instabilities, attention span, verbal intelligence quotient, and brain microstructure changes. A study compared thirty-three children diagnosed with type 1 diabetes and with a history of DKA to twenty-nine children with type 1 diabetes and no DKA history. These treatment arms assessed the children’s capability to remember events with precise details and memory functions affected by hypoxia. It was concluded that children with DKA had significantly lesser performance in specific memory abilities.  

This study aims to determine if a diabetic ketoacidosis episode in a child causes cognitive function to decline, in both children who were recently diagnosed with type 1 diabetes and in children who had been previously diagnosed, after taking into account variations in glucose control and other relevant factors. This randomized multisite clinical study closes the gap exploring the correlations of DKA occurrence and severity to cognitive function. In this trial, the study arms were 430 children with moderate/serve DKA, 328 children with mild DKA, and 376 children with non-DKA. Seven hundred fifty-eight children joined this study prospectively, aged 6 to 18 years old; three hundred ninety-two children presenting with DKA and new onset of type 1 diabetes. The outcomes related to cognitive effects in children with moderate or severe DKA, mild DKA, or no DKA history. The cognitive assessments included color tasks, intelligence quotient, and digit span recall. The statistical test used to test the DKA functions’ differences was the likelihood ratio test and ANOVA test. Chi-squared and Wilcoxon rank-sum tests were used to determine if patients with a DKA history that finished the cognitive assessments were different from people who did not make it to the follow-up. 

Between all the patients in this trial, moderate/severe DKA was related to a lower intelligence quotient. The beta was -0.12, and the p-value was < 0.001, the item-color recall beta was -0.08, the p-value was 0.010, and the forward digit span beta was -0.06, the p-value was 0.04. In the newly diagnosed patients in the arm, moderate/severe DKA had lower item-color, and the beta was -0.08, and the p-value was 0.04. The previously diagnosed patients experienced frequent DKA exposure and had higher HbA1C independently associated with lower IQ. After considering hypoglycemia, diabetes duration, and socioeconomic status, the beta was -0.10 and -0.09, respectively, p-value < 0.01. Higher HbA1C was associated with the lower item-color recall, a beta of -0.10, and a p-value of 0.007.  

This study found that even one DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. For children with known diabetes, more sizable IQ declines were detected, suggesting that DKA effects are worsened in children with chronic exposure to hyperglycemia. 

Practice Pearls: 

• DKA is a preventable and severe complication associated with type 1 diabetes.  
• Following a single DKA episode soon after the diagnosis of type 1 diabetes, memory function declines.  
• Chronic exposure to hyperglycemia seems to worsen DKA effects, and to have an impact on IQ. 

Ghetti S, Lee JK, Sims CE, DeMaster DM, Glaser NS. Diabetic Ketoacidosis and Memory Dysfunction in Children with Type 1 Diabetes. J Pediatr. 2010;156(1):109-114. doi:10.1016/j.jpeds.2009.07.054 

Glaser NS, Wootton-Gorges SL, Buonocore MH, et al. Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis. Pediatr Diabetes. 2006;7(2):75 doi:10.1111/j.1399-543X.2006.00156.x

Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes. Published online, 2020. doi:10.2337/dc20-0187 

Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical University, College  of Pharmacy and Pharmaceutical Sciences