Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed type 1 diabetes

Pediatric Emergency Care Applied Research Network (PECARN) DKA FLUID Study Group

doi:10.2337/dc20-0187

Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed type 1 diabetes

Pediatric Emergency Care Applied Research Network (PECARN) DKA FLUID Study Group

Pediatrics

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

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) (b 5 20.12, P < 0.001), item-color recall (b 5 20.08, P 5 0.010), and forward digit span (b 5 20.06, P 5 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (b 520.08, P 5 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA_1c were independently associated with lower IQ (b 5 20.10 and b 5 20.09, respectively, P < 0.01) and higher HbA_1c was associated with lower item-color recall (b 5 20.10, P 5 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.

Original language	English (US)
Pages (from-to)	2768-2775
Number of pages	8
Journal	Diabetes care
Volume	43
Issue number	11
DOIs	https://doi.org/10.2337/dc20-0187
State	Published - Nov 2020

Funding

Acknowledgments. The authors thank Marci Fjelstad and Amy Watson from the PECARN Data Coordinating Center for their assistance; the research coordinators in PECARN, without whom this trial would not have been possible; the clinicians in PECARN who enrolled children into this study; the members of the data and safety monitoring board (Roger Lewis [Department of Emergency Medicine, Harbor-UCLA Medical Center], Jeffrey Blumer [School of Medicine, Case Western Reserve University], Andrew Bremer [National Institute of Child and Human Development], Thomas Cook [Department of Biostatistics and Medical Informatics, University of Wisconsin], and Beth Slomine [Department of Psychiatry, Johns Hopkins University School of Medicine]); and the members of the study outcome adjudication committee (Kathleen Meert [Department of Pediatrics, Children’s Hospital of Michigan], Jerry Zimmerman [Center for Clinical and Translational Research, Seattle Children’s Hospital], and Robert Hickey [Division of Pediatric Emergency Medicine, Children’s Hospital of Pittsburgh]). Funding. This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD062417). This project was also supported in part by the Health Resources and Services Administration, Maternal and Child Health Bureau, and Emergency Medical Services for Children Network Development Demonstration Program under cooperative agreement numbers U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685. This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD062417). This project was also supported in part by the Health Resources and Services Administration, Maternal and Child Health Bureau, and Emergency Medical Services for Children Network Development Demonstration Program under cooperative agreement numbers U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685.

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Advanced and Specialized Nursing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/dc20-0187

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@article{3388565e65de42319d08dafe621c0591,

title = "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) (b 5 20.12, P < 0.001), item-color recall (b 5 20.08, P 5 0.010), and forward digit span (b 5 20.06, P 5 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (b 520.08, P 5 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (b 5 20.10 and b 5 20.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (b 5 20.10, P 5 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.",

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

note = "Publisher Copyright: {\textcopyright} 2020 by the American Diabetes Association.",

year = "2020",

month = nov,

doi = "10.2337/dc20-0187",

language = "English (US)",

volume = "43",

pages = "2768--2775",

journal = "Diabetes care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "11",

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TY - JOUR

T1 - Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed type 1 diabetes

AU - Pediatric Emergency Care Applied Research Network (PECARN) DKA FLUID Study Group

AU - Ghetti, Simona

AU - Kuppermann, Nathan

AU - Rewers, Arleta

AU - Myers, Sage R.

AU - Schunk, Jeff E.

AU - Stoner, Michael J.

AU - Garro, Aris

AU - Quayle, Kimberly S.

AU - Brown, Kathleen M.

AU - Trainor, Jennifer L.

AU - Tzimenatos, Leah

AU - Depiero, Andrew D.

AU - McManemy, Julie K.

AU - Nigrovic, Lise E.

AU - Kwok, Maria Y.

AU - Perry, Clinton S.

AU - Olsen, Cody S.

AU - Casper, T. Charles

AU - Glaser, Nicole S.

PY - 2020/11

Y1 - 2020/11

N2 - 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) (b 5 20.12, P < 0.001), item-color recall (b 5 20.08, P 5 0.010), and forward digit span (b 5 20.06, P 5 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (b 520.08, P 5 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (b 5 20.10 and b 5 20.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (b 5 20.10, P 5 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.

AB - 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) (b 5 20.12, P < 0.001), item-color recall (b 5 20.08, P 5 0.010), and forward digit span (b 5 20.06, P 5 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (b 520.08, P 5 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (b 5 20.10 and b 5 20.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (b 5 20.10, P 5 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.

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Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed type 1 diabetes

Abstract

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UN SDGs

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