Cognitive Function following Diabetic Ketoacidosis in Children with New Onset or Previously Diagnosed Type 1 Diabetes

Objective. This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes, and whether the same is true in children who had been previously diagnosed after accounting for variations in glycemic control and other relevant factors. Design. We prospectively enrolled 758 children, 6- to 18-years-old, who presented with DKA in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. Results. Among all patients, moderate/severe DKA was associated with lower IQ (β=-.12, p<0.001), item-color recall (β=-0.08, p=0.010), and forward digit span (β=-0.06, p=0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β=-0.08, p=0.04). Among previously diagnosed patients, repeated DKA exposure and higher hemoglobin A1c were independently associated with lower IQ (β=-.10 and β=-0.09, respectively, ps <.01) and higher hemoglobin A1c was associated with lower item-color recall (β=-0.10, p=0.007), after accounting for hypoglycemia, diabetes duration, and socio-economic status. Conclusion. A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.