Impact of Early Diabetic Ketoacidosis on the Developing Brain

Author:

Aye Tandy1ORCID,Mazaika Paul K.2ORCID,Mauras Nelly3,Marzelli Matthew J.2,Shen Hanyang2,Hershey Tamara4,Cato Allison5,Weinzimer Stuart A.6,White Neil H.7,Tsalikian Eva8,Jo Booil2,Reiss Allan L.29,Tsalikian Eva,Tansey Michael J.,Coffey Julie,Cabbage Joanne,Salamati Sara,Mauras Nelly,Fox Larry A.,Cato Allison,Englert Kim,Sikes Kaitlin,Buckingham Bruce A.,Wilson Darrell M.,Aye Tandy,Caswell Kimberly,Ambers Ellen,Weinzimer Stuart A.,Tamborlane William V.,Steffen Amy,Weyman Kate,Zgorski Melinda,Ambrosino Jodie,White Neil H.,Arbelaez Ana Maria,Levandoski Lucy,Starnes Angie,Hershey Tamara,Reiss Allan L.,Barnea-Goraly Naama,Marzelli Matthew J.,Mazaika Paul K.,Peng Daniel X.,Beck Roy,Kollman Craig,Ruedy Katrina,Winer Karen,Sperling Mark,Becker Dorothy M.,Cleary Patricia,Greenbaum Carla,Moran Antoinette,

Affiliation:

1. Division of Pediatric Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA

2. Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA

3. Division of Pediatric Endocrinology, Department of Pediatrics, Nemours Children’s Health System, Jacksonville, FL

4. Departments of Psychiatry and Radiology, Washington University School of Medicine, St. Louis, MO

5. Division of Neurology, Department of Pediatrics, Nemours Children’s Health System, Jacksonville, FL

6. Section of Pediatric Endocrinology, Department of Pediatrics, Yale University, New Haven, CT

7. Division of Endocrinology and Diabetes, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO

8. Division of Endocrinology and Diabetes, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA

9. Departments of Radiology and Pediatrics, Stanford University School of Medicine, Stanford, CA

Abstract

OBJECTIVE This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes. RESEARCH DESIGN AND METHODS Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months. RESULTS In 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores and cognitive performance on the Detectability and Commission subtests of the Conners’ Continuous Performance Test II and the Dot Locations subtest of the Children’s Memory Scale. CONCLUSIONS A single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain.

Funder

National Institute of Child Health and Human Development

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

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