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

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posted on 22.09.2020 by Simona Ghetti, Nathan Kuppermann, Arleta Rewers, Sage R. Myers, Jeff E. Schunk, Michael J. Stoner, Aris Garro, Kimberly S. Quayle, Kathleen M. Brown, Jennifer L. Trainor, Leah Tzimenatos, Andrew D. DePiero, Julie K. McManemy, Lise E. Nigrovic, Maria Y. Kwok, Clinton S. Perry III, Cody S. Olsen, T. Charles Casper, Nicole S. Glaser, The Pediatric Emergency Care Applied Research Network (PECARN) DKA FLUID Study Group
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.

Funding

This study was supported by grant U01HD062417 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. This project was also supported in part by the Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB), Emergency Medical Services for Children (EMSC) Network Development Demonstration Program under cooperative agreement number U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684 and U03MC22685. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government.

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