Relationships among biochemical measures in children with diabetic ketoacidosis

Nicole S. Glaser; Michael J. Stoner; Maria Y. Kwok; Kimberly S. Quayle; Kathleen M. Brown; Jeff E. Schunk; Jennifer L. Trainor; Julie K. McManemy; Leah Tzimenatos; Arleta Rewers; Lise E. Nigrovic; Jonathan E. Bennett; Sage R. Myers; McKenna Smith; T. Charles Casper; Nathan Kuppermann

doi:10.1515/jpem-2022-0570

Article

Relationships among biochemical measures in children with diabetic ketoacidosis

Nicole S. Glaser , Michael J. Stoner , Maria Y. Kwok , Kimberly S. Quayle , Kathleen M. Brown , Jeff E. Schunk , Jennifer L. Trainor , Julie K. McManemy , Leah Tzimenatos , Arleta Rewers , Lise E. Nigrovic , Jonathan E. Bennett , Sage R. Myers , McKenna Smith , T. Charles Casper and Nathan Kuppermann

Published/Copyright: January 16, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 36 Issue 3

Abstract

Objectives

Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.

Methods

We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO₂ at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.

Results

pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO₂ were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO₂ levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19).

Conclusions

Elevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO₂ are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

Keywords: acid-base balance; diabetes; diabetic ketoacidosis; electrolytes

Corresponding author: Nicole Glaser, MD, Department of Pediatrics, University of California Davis, School of Medicine, 2516 Stockton Blvd., Sacramento, CA, 95817, USA, Phone: (916) 734 7098, Fax: (916) 734 7070, E-mail: nsglaser@ucdavis.edu

A complete list of non-author members of the PECARN DKA FLUID Study Group appears in the Acknowledgments.

Funding source: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Award Identifier / Grant number: U01HD062417

Funding source: Maternal and Child Health Bureau

Award Identifier / Grant number: U03MC00008, U03MC00001, U03MC00003, U03MC00006, U0

Acknowledgments

We gratefully acknowledge the participation of our beloved colleague, Aris Garro, MD, MPH (deceased), as co-investigator in this study. Participating co-investigators of the PECARN DKA FLUID Study Group at the time of the design and initiation of the study included the following: UC Davis Medical Center Health, University of California Davis: Simona Ghetti, PhD, Clinton S. Perry III, PhD, James P. Marcin, MD, MPH. Primary Children’s Medical Center, University of Utah: Mary Murray, MD, Jared Henricksen, MD, Brad Poss, MD, J. Michael Dean, MD, MBA. Nationwide Children’s Hospital, Ohio State University: Bema Bonsu, MD, Tensing Maa, MD. Justin Indyk, MD, PhD. Children’s Hospital Colorado, University of Colorado: Marian Rewers, MD, PhD. Peter Mourani, MD. Texas Children’s Hospital, Baylor University. Jake A. Kushner, MD, Laura L. Loftis, MD. Children’s Hospital of Philadelphia, University of Pennsylvania. Monika Goyal, MD, MSCE, Rakesh Mistry, MD, MS, Vijay Srinivasan, MD, Andrew Palladino, MD, Boston Children’s Hospital, Harvard Medical School. Joseph I. Wolfsdorf, MD, Michael S. Agus, MD. Rhode Island Hospital, Brown University, Aris Garro, MD, MPH, Linda Snelling, MD, Charlotte Boney, MD, MS (University of Massachusetts Medical School, Baystate), Children’s National Medical Center, George Washington University, Fran R. Cogen, MD, CDE, Sonali Basu, MD, St. Louis Children’s Hospital, Washington University in St. Louis, Neil H. White, MD, CDE, Nikoleta S. Kolovos, MD, Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University, Donald Zimmerman, MD, Denise Goodman, MD, MS, A.I. DuPont Hospital for Children, Thomas Jefferson University, Andrew D. DePiero, MD, Daniel A. Doyle, MD, Meg A. Frizzola, MD, New York Presbyterian Morgan Stanley Children’s Hospital, Columbia University, David Schnadower, MD, Mary Pat Gallagher, MD, John Scott Baird, MD.

Research funding: Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant U01HD062417) and the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration, under cooperative agreement (awards U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685). The content and conclusions of this article are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by the Health Resources and Services Administration, the Department of Health and Human Services, or the U.S. government. The funding organizations played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: None of the authors have conflicts of interest relevant to the manuscript.
Informed consent: Informed consent was obtained from all individuals included in the PECARN FLUID Trial database. Consent was not required for medical records review for the additional DKA episodes added later to the FLUID Trial database.
Ethical approval: The research related to human use has complied with all of the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration. The Institutional Review Boards at each of the participating institutions approved the study protocol as well as additional medical record review.

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Received: 2022-11-08

Accepted: 2022-12-14

Published Online: 2023-01-16

Published in Print: 2023-03-28

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https://doi.org/10.1515/jpem-2022-0570

Keywords for this article

acid-base balance; diabetes; diabetic ketoacidosis; electrolytes