Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes

Abstract

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 previously been diagnosed after accounting for variations in glycemic control and other relevant factors.

Research design and methods: We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 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 intelligence quotient (IQ) (β = -0.12, 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 HbA_1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA_1c was associated with lower item-color recall (β = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for.

Conclusions: 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.

Figure 1

Interaction effect between DKA status and levels of SES among previously diagnosed patients. Estimates and 95% CIs of IQ average over other effects in a multivariable mixed linear regression model, which included sex, duration of diabetes, previous DKA episodes, history of severe hypoglycemia, HbA_1c, and study site. GED, General Educational Development.