Simona Ghetti1,2, Nathan Kuppermann3,4, Arleta Rewers5, Sage R Myers6, Jeff E Schunk7, Michael J Stoner8, Aris Garro9, Kimberly S Quayle10, Kathleen M Brown11, Jennifer L Trainor12, Leah Tzimenatos3, Andrew D DePiero13, Julie K McManemy14, Lise E Nigrovic15, Maria Y Kwok16, Clinton S Perry2,17, Cody S Olsen7, T Charles Casper7, Nicole S Glaser. 1. Department of Psychology, University of California, Davis, Davis, CA sghetti@ucdavis.edu. 2. Center for Mind and Brain, University of California, Davis, Davis, CA. 3. Department of Emergency Medicine, UC Davis Health, UC Davis School of Medicine, Sacramento, CA. 4. Department of Pediatrics, UC Davis Health, UC Davis School of Medicine, Sacramento, CA. 5. Division of Emergency Medicine, Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, University of Colorado Denver, Aurora, CO. 6. Division of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 7. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT. 8. Division of Emergency Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH. 9. Departments of Emergency Medicine and Pediatrics, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence, RI. 10. Division of Emergency Medicine, Department of Pediatrics, St. Louis Children's Hospital, Washington University School of Medicine in St. Louis, St. Louis, MO. 11. Division of Emergency Medicine, Department of Pediatrics, Children's National Medical Center, The School of Medicine & Health Sciences, The George Washington University, Washington, DC. 12. Division of Emergency Medicine, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL. 13. Division of Emergency Medicine, Nemours/Alfred I. duPont Hospital for Children, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA. 14. Division of Emergency Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX. 15. Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA. 16. Division of Emergency Medicine, Department of Pediatrics, New York Presbyterian Morgan Stanley Children's Hospital, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. 17. Department of Psychology, Tufts University, Medford, MA.
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 HbA1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA1c 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.
RCT Entities:
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 HbA1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA1c 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.
Authors: Nicole S Glaser; Sandra L Wootton-Gorges; Michael H Buonocore; James P Marcin; Arleta Rewers; John Strain; Joseph DiCarlo; E Kirk Neely; Patrick Barnes; Nathan Kuppermann Journal: Pediatr Diabetes Date: 2006-04 Impact factor: 4.866
Authors: N Glaser; P Barnett; I McCaslin; D Nelson; J Trainor; J Louie; F Kaufman; K Quayle; M Roback; R Malley; N Kuppermann Journal: N Engl J Med Date: 2001-01-25 Impact factor: 91.245
Authors: S L Wootton-Gorges; M H Buonocore; N Kuppermann; J P Marcin; P D Barnes; E K Neely; J DiCarlo; T McCarthy; N S Glaser Journal: AJNR Am J Neuroradiol Date: 2007-05 Impact factor: 3.825
Authors: Nathan Kuppermann; Simona Ghetti; Jeff E Schunk; Michael J Stoner; Arleta Rewers; Julie K McManemy; Sage R Myers; Lise E Nigrovic; Aris Garro; Kathleen M Brown; Kimberly S Quayle; Jennifer L Trainor; Leah Tzimenatos; Jonathan E Bennett; Andrew D DePiero; Maria Y Kwok; Clinton S Perry; Cody S Olsen; T Charles Casper; J Michael Dean; Nicole S Glaser Journal: N Engl J Med Date: 2018-06-14 Impact factor: 91.245
Authors: Tandy Aye; Paul K Mazaika; Nelly Mauras; Matthew J Marzelli; Hanyang Shen; Tamara Hershey; Allison Cato; Stuart A Weinzimer; Neil H White; Eva Tsalikian; Booil Jo; Allan L Reiss Journal: Diabetes Care Date: 2018-12-20 Impact factor: 19.112
Authors: Nicole Glaser; Steven Chu; Justin Weiner; Linnea Zdepski; Heike Wulff; Daniel Tancredi; Martha E ODonnell Journal: BMJ Open Diabetes Res Care Date: 2022-05
Authors: Hugo Segerer; Michael Wurm; Julia M Grimsmann; Beate Karges; Andreas Neu; Marina Sindichakis; Katharina Warncke; Axel Dost; Reinhard W Holl Journal: Dtsch Arztebl Int Date: 2021-06-04 Impact factor: 5.594
Authors: Arleta Rewers; Nathan Kuppermann; Michael J Stoner; Aris Garro; Jonathan E Bennett; Kimberly S Quayle; Jeffrey E Schunk; Sage R Myers; Julie K McManemy; Lise E Nigrovic; Jennifer L Trainor; Leah Tzimenatos; Maria Y Kwok; Kathleen M Brown; Cody S Olsen; T Charles Casper; Simona Ghetti; Nicole S Glaser Journal: Diabetes Care Date: 2021-06-29 Impact factor: 17.152