Biochemical Testing and Thresholds for Diagnosing Diabetic Ketoacidosis in Children and Adolescents without Known Diabetes Mellitus: Systematic Review and Meta-Analysis

Abstract

Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of Type 1 Diabetes Mellitus (T1DM). Although international guidelines propose biochemical criteria for diagnosis, inconsistencies in threshold values and their application in clinical practice persist, particularly for children with previously undiagnosed T1DM. We conducted this systematic review to evaluate what plasma glucose levels and other biochemical tests are indicative of DKA in children and adolescents presenting without known T1DM.

Methods: We conducted a systematic review in accordance with PRISMA guidelines (PROSPERO ID: CRD42024621961) and searched PubMed, CINAHL, Cochrane, and Scopus for studies reporting biochemical diagnostic criteria of DKA in children aged 0-19 years. The quality of included studies was assessed using the National Institutes of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A proportional meta-analysis was conducted on Stata 17 to estimate the pooled incidence.

Results: We included 97 studies involving 159,585 participants. Most studies (n = 71, 73%) originated from high-income settings. No study directly compared different biochemical thresholds for diagnosing DKA. Across 77 studies, 12 distinct criteria were identified that used a combination of blood glucose, venous pH, bicarbonate, ketonemia, and ketonuria, while the remaining 20 studies used author-defined criteria. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guideline was the most frequently reported, with a pooled DKA incidence of 39% (95% CI = 35%,44%, certainty of evidence: low). Heterogeneity across studies, as measured by different diagnostic criteria, was high (I² > 80%). Subgroup analysis showed a higher incidence of DKA (56%, 95% CI = 50%, 62%) in children aged 0-9 years.

Conclusion: This systematic review highlights significant global variation in the biochemical definitions used to diagnose and classify DKA in children and adolescents. Standardization of diagnostic criteria is essential to improve early detection and reduce DKA-related morbidity and mortality.

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© 2025 Ariff S. Distributed under Creative Commons CC-BY 4.0

How to cite this article

Memon F, Alam R, Idrees H, Ishaq A, Soofi S, Ariff S. Biochemical Testing and Thresholds for Diagnosing Diabetic Ketoacidosis in Children and Adolescents without Known Diabetes Mellitus: Systematic Review and Meta-Analysis. J Biomed Res Environ Sci. 2025 Sept 20; 6(9): 1342-1352. doi: 10.37871/jbres2189, Article ID: JBRES2189, Available at: https://www.jelsciences. com/articles/jbres2189.pdf

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