{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:12:19Z","timestamp":1792001539025,"version":"4.4.0"},"reference-count":118,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Diabetic ketoacidosis is the most common acute complication in children and adolescents with type 1 diabetes, and contributes significantly to morbidity, mortality, and healthcare burden. This review aims to explore the multifaceted aspects of severe diabetic ketoacidosis in pediatric age, including its epidemiology, pathogenesis, risk factors, complications and emphasizing advances in prevention strategies. Incidence rates vary due to influences from geographic, socioeconomic, cultural and demographic factors. Pathogenesis is linked to insulin deficiency and an excess of counter-regulatory hormones, which disrupt glucose, protein, and lipid metabolism, causing hyperglycemia, ketosis, acidosis, dehydration, and electrolyte imbalances. According to the International Society for Pediatric and Adolescent Diabetes guidelines, severe diabetic ketoacidosis is characterized by a pH &lt; 7.1 or bicarbonate &lt; 5 mmol\/L. This condition can lead to a wide range of life-threatening complications, including cerebral edema that represents the leading cause of death. Several prevention strategies, including awareness campaigns, early diagnosis of diabetes, regular monitoring and management, effective insulin therapy, education, access to healthcare and technological assistance, may contribute to reduce the risk of severe diabetic ketoacidosis episodes in children and adolescents.<\/jats:p>","DOI":"10.3390\/children12010110","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:04:12Z","timestamp":1737345852000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Severe Diabetic Ketoacidosis in Children with Type 1 Diabetes: Ongoing Challenges in Care"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-5605","authenticated-orcid":false,"given":"Simone","family":"Foti Randazzese","sequence":"first","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"La Rocca","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8664-1025","authenticated-orcid":false,"given":"Bruno","family":"Bombaci","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Di Pisa","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u00e8na","family":"Giliberto","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Inturri","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Militi","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloisa","family":"Gitto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neonatal and Pediatric Intensive Care Unit, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Salzano","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cG. 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Primers."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1684175","DOI":"10.1155\/2018\/1684175","article-title":"Common Issues Seen in Paediatric Diabetes Clinics, Psychological Formulations, and Related Approaches to Management","volume":"2018","author":"Deeb","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/pedi.13406","article-title":"ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state","volume":"23","author":"Glaser","year":"2022","journal-title":"Pediatr. Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2337\/diacare.24.1.131","article-title":"Management of hyperglycemic crises in patients with diabetes","volume":"24","author":"Kitabchi","year":"2001","journal-title":"Diabetes Care."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ecl.2006.09.006","article-title":"Hyperglycemic crises in diabetes mellitus: Diabetic ketoacidosis and hyperglycemic hyperosmolar state","volume":"35","author":"Kitabchi","year":"2006","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-nutr-111120-111518","article-title":"Metabolic and Signaling Roles of Ketone Bodies in Health and Disease","volume":"41","author":"Puchalska","year":"2021","journal-title":"Annu. Rev. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kostopoulou, E., Sinopidis, X., Fouzas, S., Gkentzi, D., Dassios, T., Roupakias, S., and Dimitriou, G. (2023). Diabetic Ketoacidosis in Children and Adolescents; Diagnostic and Therapeutic Pitfalls. Diagnostics, 13.","DOI":"10.20944\/preprints202306.1909.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1097\/MS9.0000000000000894","article-title":"Comprehensive review of diabetic ketoacidosis: An update","volume":"85","author":"Elendu","year":"2023","journal-title":"Ann. Med. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11702","DOI":"10.12998\/wjcc.v10.i32.11702","article-title":"Overlap of diabetic ketoacidosis and hyperosmolar hyperglycemic state","volume":"10","author":"Hassan","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"932","DOI":"10.4239\/wjd.v5.i6.932","article-title":"Risk factors for mortality in children with diabetic ketoacidosis from developing countries","volume":"5","author":"Poovazhagi","year":"2014","journal-title":"World J. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1089\/dia.2023.0149","article-title":"Prevalence, Cost, and Burden of Diabetic Ketoacidosis","volume":"25","author":"Virdi","year":"2023","journal-title":"Diabetes Technol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2147\/PHMT.S384104","article-title":"Pediatric Diabetes and Diabetic Ketoacidosis After COVID-19: Challenges Faced and Lessons Learnt","volume":"14","author":"Agarwal","year":"2023","journal-title":"Pediatric Health Med Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1034\/j.1399-5448.2003.00007.x","article-title":"Ketoacidosis at onset of type 1 diabetes mellitus in children\u2014frequency and clinical presentation","volume":"4","author":"Neu","year":"2003","journal-title":"Pediatr. Diabetes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"350","DOI":"10.7326\/0003-4819-144-5-200603070-00011","article-title":"Ketosis-prone type 2 diabetes mellitus","volume":"144","author":"Umpierrez","year":"2006","journal-title":"Ann. Int. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"971","DOI":"10.4158\/EP161679.RA","article-title":"Diabetic Ketoacidosis: A Common Debut of Diabetes Among African Americans with Type 2 Diabetes","volume":"23","author":"Vellanki","year":"2017","journal-title":"Endocr. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 14. Children and Adolescents: Standards of Care in Diabetes-2025. Diabetes Care., 48, S283\u2013S305.","DOI":"10.2337\/dc25-S014"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1111\/pedi.12891","article-title":"Using population data to understand the epidemiology and risk factors for diabetic ketoacidosis in Australian children with type 1 diabetes","volume":"20","author":"Ampt","year":"2019","journal-title":"Pediatr. Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e938","DOI":"10.1542\/peds.2013-2795","article-title":"Trends in the prevalence of ketoacidosis at diabetes diagnosis: The SEARCH for diabetes in youth study","volume":"133","author":"Dabelea","year":"2014","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1007\/s00125-012-2690-2","article-title":"Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: A systematic review","volume":"55","author":"Thompson","year":"2012","journal-title":"Diabetologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.numecd.2020.06.006","article-title":"Diabetic ketoacidosis: A consensus statement of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology and Pediatric Diabetoloy (SIEDP)","volume":"30","author":"Lapolla","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"46","DOI":"10.4274\/jcrpe.galenos.2022.2022-5-8","article-title":"Frequency, Clinical Characteristics and Predictors of Ketoacidosis at Diagnosis of Type One Diabetes Mellitus in Children and Adolescents from Jordan","volume":"15","author":"Odeh","year":"2023","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_22","unstructured":"Cherubini, V., Skrami, E., Ferrito, L., Zucchini, S., Scaramuzza, A., Bonfanti, R., Buono, P., Cardella, F., Cauvin, V., and Chiari, G. (2016). High frequency of diabetic ketoacidosis at diagnosis of type 1 diabetes in Italian children: A nationwide longitudinal study, 2004\u20132013. Sci. Rep., 6."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Atkilt, H.S., Turago, M.G., and Tegegne, B.S. (2017). Clinical Characteristics of Diabetic Ketoacidosis in Children with Newly Diagnosed Type 1 Diabetes in Addis Ababa, Ethiopia: A Cross-Sectional Study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169666"},{"key":"ref_24","first-page":"367","article-title":"Diabetic Ketoacidosis at Manifestation of Type 1 Diabetes in Childhood and Adolescence\u2014Incidence and Risk Factors","volume":"118","author":"Segerer","year":"2021","journal-title":"Dtsch Arztebl. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1001\/jamapediatrics.2021.5801","article-title":"Incidence of New-Onset Type 1 Diabetes Among US Children During the COVID-19 Global Pandemic","volume":"176","author":"Gottesman","year":"2022","journal-title":"JAMA Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.2337\/dc20-1321","article-title":"Has COVID-19 Delayed the Diagnosis and Worsened the Presentation of Type 1 Diabetes in Children?","volume":"43","author":"Rabbone","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1080\/1744666X.2023.2189587","article-title":"Examining the associations between COVID-19 infection and pediatric type 1 diabetes","volume":"19","author":"Bombaci","year":"2023","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5112","DOI":"10.1002\/jmv.27996","article-title":"The global impact of COVID-19 pandemic on the incidence of pediatric new-onset type 1 diabetes and ketoacidosis: A systematic review and meta-analysis","volume":"94","author":"Rahmati","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.12688\/f1000research.128687.2","article-title":"Impact of the COVID-19 pandemic on the incidence and clinical outcomes of diabetic ketoacidosis among male and female children with type 1 diabetes: Systematic review and meta-analysis","volume":"12","year":"2023","journal-title":"F1000Res"},{"key":"ref_30","unstructured":"Cherubini, V., Marino, M., Scaramuzza, A.E., Tiberi, V., Bobbio, A., Delvecchio, M., Piccinno, E., Ortolani, F., Innaurato, S., and Felappi, B. (2022). The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020. Front. Endocrinol., 13."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e132809","DOI":"10.5812\/ijem-132809","article-title":"Diabetic Ketoacidosis in Children Before and During COVID-19 Pandemic: A Cross-sectional Study","volume":"21","author":"Ordooei","year":"2023","journal-title":"Int. J. Endocrinol. Metab."},{"key":"ref_32","first-page":"103","article-title":"Pediatric Diabetic Ketoacidosis: A Retrospective Study on Triggering Factors and Complications in a Turkish Intensive Care Unit","volume":"11","author":"Ermaydan","year":"2024","journal-title":"J. Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13052-023-01448-1","article-title":"Prevalence and clinical features of severe diabetic ketoacidosis treated in pediatric intensive care unit: A 5-year monocentric experience","volume":"49","author":"Passanisi","year":"2023","journal-title":"Ital. J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lah Tomuli\u0107, K., Matko, L., Verbi\u0107, A., Milardovi\u0107, A., Severinski, S., Koli\u0107, I., Baraba Dekani\u0107, K., \u0160erifi, S., and Butorac Ahel, I. (2022). Epidemiologic Characteristics of Children with Diabetic Ketoacidosis Treated in a Pediatric Intensive Care Unit in a 10-Year-Period: Single Centre Experience in Croatia. Medicina, 58.","DOI":"10.3390\/medicina58050638"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6693226","DOI":"10.1155\/2023\/6693226","article-title":"Emergency Department Presentations of Diabetic Ketoacidosis in a Large Cohort of Children","volume":"2023","author":"Nigrovic","year":"2023","journal-title":"Pediatr. Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejim.2023.07.005","article-title":"Management of diabetic ketoacidosis","volume":"117","author":"Barski","year":"2023","journal-title":"Eur. J. Intern Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s11892-012-0307-2","article-title":"Current concepts and controversies in prevention and treatment of diabetic ketoacidosis in children","volume":"12","author":"Rewers","year":"2012","journal-title":"Curr. Diab. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.jemermed.2013.03.040","article-title":"Hyperglycemic crisis","volume":"45","author":"Hack","year":"2013","journal-title":"J. Emerg. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.metabol.2015.12.007","article-title":"The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management","volume":"65","author":"Nyenwe","year":"2016","journal-title":"Metabolism"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.jemermed.2020.06.059","article-title":"Evaluation and Management of the Critically Ill Adult with Diabetic Ketoacidosis","volume":"59","author":"Long","year":"2020","journal-title":"J. Emerg. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrendo.2016.15","article-title":"Diabetic emergencies\u2014ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia","volume":"12","author":"Umpierrez","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, P., Lozano, P., Ros, G., and Solano, F. (2023). Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119352"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11010-021-04260-9","article-title":"Modulation of endothelium function by fatty acids","volume":"477","author":"Mallick","year":"2022","journal-title":"Mol. Cell Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1530\/EJE-15-0129","article-title":"Hospital admission for diabetic ketoacidosis or severe hypoglycemia in 31,330 young patients with type 1 diabetes","volume":"173","author":"Karges","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1001\/jama.287.19.2511","article-title":"Predictors of acute complications in children with type 1 diabetes","volume":"287","author":"Rewers","year":"2002","journal-title":"JAMA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00023210-200519001-00001","article-title":"Second generation (atypical) antipsychotics and metabolic effects: A comprehensive literature review","volume":"19","author":"Newcomer","year":"2005","journal-title":"CNS Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/dme.13519","article-title":"Inequalities in glycaemic control, hypoglycaemia and diabetic ketoacidosis according to socio-economic status and area-level deprivation in type 1 diabetes mellitus: A systematic review","volume":"35","author":"Lindner","year":"2018","journal-title":"Diabet. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1210\/jc.2018-02232","article-title":"Association of area deprivation and diabetic ketoacidosis readmissions: Comparative risk analysis of adults vs children with type 1 diabetes","volume":"104","author":"Everett","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejim.2019.03.014","article-title":"Euglycemic diabetic ketoacidosis","volume":"63","author":"Barski","year":"2019","journal-title":"Eur. J. Intern. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000053320","article-title":"Recurrent diabetic ketoacidosis: Causes, prevention and management","volume":"57","author":"Skinner","year":"2002","journal-title":"Horm. Res. Paediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e150","DOI":"10.2337\/dc18-1465","article-title":"Increased Reporting of Immune Checkpoint Inhibitor-Associated Diabetes","volume":"41","author":"Wright","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S2213-8587(15)00135-7","article-title":"Constructs of depression and distress in diabetes: Time for an appraisal","volume":"3","author":"Snoek","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S259","DOI":"10.4103\/2230-8210.104055","article-title":"Continuous subcutaneous insulin infusion: Practical issues","volume":"16","author":"Saboo","year":"2012","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"22","DOI":"10.4158\/EP.13.1.22","article-title":"Active use of cocaine: An independent risk factor for recurrent diabetic ketoacidosis in a city hospital","volume":"13","author":"Nyenwe","year":"2007","journal-title":"Endocr. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00592-010-0243-z","article-title":"Recreational drug abuse in patients hospitalized for diabetic ketosis or diabetic ketoacidosis","volume":"50","author":"Isidro","year":"2013","journal-title":"Acta Diabetol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.2337\/dc16-0668","article-title":"An Evaluation of Recurrent Diabetic Ketoacidosis, Fragmentation of Care, and Mortality Across Chicago, Illinois","volume":"39","author":"Mays","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106","DOI":"10.12669\/pjms.341.13875","article-title":"Spectrum of complications of severe DKA in children in pediatric Intensive Care Unit","volume":"34","author":"Abbas","year":"2018","journal-title":"Pak J. Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"167","DOI":"10.4239\/wjd.v6.i1.167","article-title":"Rare complications of pediatric diabetic ketoacidosis","volume":"6","author":"Bialo","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.2337\/dc06-9909","article-title":"Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association","volume":"29","author":"Wolfsdorf","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/01.ccm.0000808152.20854.50","article-title":"Epidemiology and outcomes of children with diabetic ketoacidosis and cerebral edema 1997\u20132016","volume":"50","author":"Leoncio","year":"2022","journal-title":"Crit. Care Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e860","DOI":"10.1002\/ams2.860","article-title":"Cerebral edema associated with diabetic ketoacidosis: Two case reports","volume":"10","author":"Namatame","year":"2023","journal-title":"Acute Med. Surg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000357140","article-title":"Severe pretreatment cerebral edema in newly diagnosed type 1 diabetes","volume":"81","author":"Warncke","year":"2014","journal-title":"Horm. Res. Paediatr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/pedi.13152","article-title":"Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema","volume":"22","author":"Azova","year":"2021","journal-title":"Pediatr Diabetes"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.2337\/dc09-9032","article-title":"Hyperglycemic crises in adult patients with diabetes","volume":"32","author":"Kitabchi","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/PCC.0000000000001037","article-title":"Imaging for Cerebral Edema in Diabetic Ketoacidosis: Time to Zap the CT?","volume":"18","author":"Vavilala","year":"2017","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.5005\/jp-journals-10071-24038","article-title":"Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis","volume":"25","author":"Raghunathan","year":"2021","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/PCC.0b013e31829f6c77","article-title":"Treating cerebral edema in diabetic ketoacidosis: Caveats in extrapolating from traumatic brain injury","volume":"14","author":"Vavilala","year":"2013","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Huang, S.K., Huang, C.Y., Lin, C.H., Cheng, B.W., Chiang, Y.T., Lee, Y.C., Yeh, S.N., Chan, C.I., Chua, W.K., and Lee, Y.J. (2020). Acute kidney injury is a common complication in children and adolescents hospitalized for diabetic ketoacidosis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239160"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e189","DOI":"10.1097\/PCC.0b013e3182745675","article-title":"Pediatric Risk, Injury, Failure, Loss, End-Stage renal disease score identifies acute kidney injury and predicts mortality in critically ill children: A prospective study","volume":"14","author":"Soler","year":"2013","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/cphy.c110041","article-title":"Pathophysiology of acute kidney injury","volume":"2","author":"Basile","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e170020","DOI":"10.1001\/jamapediatrics.2017.0020","article-title":"Acute Kidney Injury in Children with Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis","volume":"171","author":"Hursh","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/pedi.12559","article-title":"Nephrolithiasis: A complication of pediatric diabetic ketoacidosis","volume":"19","author":"Agrawal","year":"2018","journal-title":"Pediatr. Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s12098-015-1961-6","article-title":"Acute Respiratory Distress Syndrome: A Rare Complication in Pediatric Diabetic Ketoacidosis","volume":"83","author":"Sudhanshu","year":"2016","journal-title":"Indian J. Pediatr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1056\/NEJMra1608077","article-title":"Acute Respiratory Distress Syndrome","volume":"377","author":"Thompson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_75","first-page":"20","article-title":"Acute respiratory distress syndrome in a case of diabetic ketoacidosis requiring ECMO support","volume":"2021","author":"Darrat","year":"2021","journal-title":"Endocrinol. Diabetes Metab Case Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"397","DOI":"10.21037\/atm.2019.07.38","article-title":"Acute coronary syndrome and diabetic keto acidosis: The chicken or the egg?","volume":"7","author":"Kaefer","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1542\/peds.113.1.e57","article-title":"Deep venous thrombosis in children with diabetic ketoacidosis and femoral central venous catheters","volume":"113","author":"Worly","year":"2004","journal-title":"Pediatrics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/PCC.0b013e31827d0e70","article-title":"Hypercoagulability among pediatric patients with diabetic ketoacidosis: The clot thickens","volume":"14","author":"Marcin","year":"2013","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Frontino, G., Di Tonno, R., Castorani, V., Rigamonti, A., Morotti, E., Sandullo, F., Scialabba, F., Arrigoni, F., Foglino, R., and Dionisi, B. (2022). Non-Occlusive Mesenteric Ischemia in Children with Diabetic Ketoacidosis: Case Report and Review of Literature. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.900325"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jpeds.2004.03.050","article-title":"Pancreatic enzyme elevations in children with diabetic ketoacidosis","volume":"145","author":"Haddad","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/gastro\/gox006","article-title":"Predictors of acute gastrointestinal bleeding in diabetic ketoacidosis: A retrospective observational study in minority population","volume":"5","author":"Badipatla","year":"2017","journal-title":"Gastroenterol. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.3748\/wjg.v16.i26.3219","article-title":"Black esophagus: Acute esophageal necrosis syndrome","volume":"16","author":"Gurvits","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9571","DOI":"10.12998\/wjcc.v9.i31.9571","article-title":"Acute esophageal necrosis as a complication of diabetic ketoacidosis: A case report","volume":"9","author":"Moss","year":"2021","journal-title":"World J. Clin. Cases."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"443","DOI":"10.2337\/dc18-1405","article-title":"Impact of Early Diabetic Ketoacidosis on the Developing Brain","volume":"42","author":"Aye","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e412","DOI":"10.1002\/edm2.412","article-title":"Cognitive function following diabetic ketoacidosis in young children with type 1 diabetes","volume":"6","author":"Ghetti","year":"2023","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4274\/jcrpe.5374","article-title":"Peripheral Neuropathy as a Complication of Diabetic Ketoacidosis in a Child with Newly Diagnosed Diabetes Type 1: A Case Report","volume":"10","author":"Szalecki","year":"2018","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jpeds.2009.10.001","article-title":"Is diabetic ketoacidosis at disease onset a result of missed diagnosis?","volume":"156","author":"Bui","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_88","first-page":"151","article-title":"Spontaneous Dissemination in Neighboring Provinces of DKA Prevention Campaign Successfully Launched in Nineties in Parma\u2019s Province","volume":"88","author":"Cangelosi","year":"2017","journal-title":"Acta Biomed."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2337\/diacare.22.1.7","article-title":"Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices","volume":"22","author":"Vanelli","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.2337\/dc07-0059","article-title":"Campaign for Diabetic Ketoacidosis Prevention Still Effective 8 Years Later","volume":"30","author":"Vanelli","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/j.1399-5448.2012.00896.x","article-title":"A diabetes awareness campaign prevents diabetic ketoacidosis in children at their initial presentation with type 1 diabetes","volume":"13","author":"King","year":"2012","journal-title":"Pediatr Diabetes"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Minerba, E., Maines, E., Quaglia, N., Fedi, L., Fanti, S., Fierro, A., and Mozzillo, E. (2024). Diabetes Awareness Campaigns to Prevent Ketoacidosis at the Diagnosis of Type 1 Diabetes: Efficacy on Multiple Outcomes and Predictors of Success: A Systematic Review. J. Pers. Med., 14.","DOI":"10.20944\/preprints202410.1959.v1"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13052-023-01438-3","article-title":"Autoantibody test for type 1 diabetes in children: Are there reasons to implement a screening program in the general population? A statement endorsed by the Italian Society for Paediatric Endocrinology and Diabetes (SIEDP-ISPED) and the Italian Society of Paediatrics (SIP)","volume":"49","author":"Cherubini","year":"2023","journal-title":"Ital. J. Pediatr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1007\/s00125-023-05953-0","article-title":"Fr1da Study Group. Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation","volume":"66","author":"Hummel","year":"2023","journal-title":"Diabetologia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.2337\/dc19-2003","article-title":"Cost and Cost-effectiveness of Large-scale Screening for Type 1 Diabetes in Colorado","volume":"43","author":"McQueen","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1111\/dom.15779","article-title":"Follow-up and monitoring programme in children identified in early-stage type 1 diabetes during screening in the general population of Italy","volume":"26","author":"Cherubini","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/pedi.13454","article-title":"ISPAD Clinical Practice Consensus Guidelines 2022: Definition, epidemiology, and classification of diabetes in children and adolescents","volume":"23","author":"Libman","year":"2022","journal-title":"Pediatr. Diabetes."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2337\/diacare.27.6.1399","article-title":"Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up","volume":"27","author":"Barker","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"610","DOI":"10.2337\/dbi20-0054","article-title":"NIDDK Type 1 Diabetes TrialNet Study Group. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective","volume":"71","author":"Sims","year":"2022","journal-title":"Diabetes"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.2337\/dc23-0675","article-title":"Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves \u03b2-Cell Function","volume":"46","author":"Herold","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"22","DOI":"10.17925\/EE.2023.19.2.7","article-title":"Teplizumab in Type 1 Diabetes Mellitus: An Updated Review","volume":"19","author":"Thakkar","year":"2023","journal-title":"touchREV Endocrinol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"eabc8980","DOI":"10.1126\/scitranslmed.abc8980","article-title":"Type 1 Diabetes TrialNet Study Group. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals","volume":"13","author":"Sims","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00592-024-02245-w","article-title":"Use of teplizumab in children and adolescents at risk of type 1 diabetes: Perspectives of parents and caregivers from an Italian Pediatric Diabetes Center","volume":"61","author":"Bombaci","year":"2024","journal-title":"Acta Diabetol."},{"key":"ref_104","unstructured":"Diamyd Medical Receives Second U.S. (2024, December 24). FDA Fast Track Designation for Diamyd\u00ae\u2014For the Prevention of Type 1 Diabetes. Available online: https:\/\/www.prnewswire.com\/news-releases\/diamyd-medical-receives-second-us-fda-fast-track-designation-for-diamyd---for-the-prevention-of-type-1-diabetes-302200405.html."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Puente-Marin, S., Dietrich, F., Achenbach, P., Barcenilla, H., Ludvigsson, J., and Casas, R. (2023). Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1112570"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1399-5448.2007.00286.x","article-title":"Can we prevent diabetic ketoacidosis in children?","volume":"8","author":"Bismuth","year":"2007","journal-title":"Pediatr. Diabetes"},{"key":"ref_107","first-page":"30","article-title":"Intensive sick day rules to prevent recurrent diabetic ketoacidosis- An intervention that exemplifies health disparities","volume":"114","author":"Dye","year":"2022","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Foti Randazzese, S., Bombaci, B., Costantino, S., Giorgianni, Y., Lombardo, F., and Salzano, G. (2024). Discordance between Glucose Management Indicator and Glycated Hemoglobin in a Pediatric Cohort with Type 1 Diabetes: A Real-World Study. Children, 11.","DOI":"10.3390\/children11020210"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/PEC.0000000000002859","article-title":"Is HbA1c an Indicator of Diabetic Ketoacidosis Severity in the Pediatric Population?","volume":"39","author":"Lamsal","year":"2023","journal-title":"Pediatr. Emerg. Care."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1089\/dia.2012.0161","article-title":"Morbidity and mortality of diabetic ketoacidosis with and without insulin pump care","volume":"14","author":"Realsen","year":"2012","journal-title":"Diabetes Technol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s41745-022-00348-3","article-title":"Emerging Diabetes Technologies: Continuous Glucose Monitors\/Artificial Pancreases","volume":"103","author":"Almurashi","year":"2023","journal-title":"J. Indian Inst. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1001\/jama.2017.13994","article-title":"Association of Insulin Pump Therapy vs Insulin Injection Therapy with Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults with Type 1 Diabetes","volume":"318","author":"Karges","year":"2017","journal-title":"JAMA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1089\/dia.2023.0341","article-title":"Real-World Use of Control-IQ Technology Is Associated with a Lower Rate of Severe Hypoglycemia and Diabetic Ketoacidosis Than Historical Data: Results of the Control-IQ Observational (CLIO) Prospective Study","volume":"26","author":"Graham","year":"2024","journal-title":"Diabetes Technol. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1177\/26350106221125699","article-title":"DKA Prevention and Insulin Pumps: Lessons Learned from a Large Pediatric Pump Practice","volume":"48","author":"Doyle","year":"2022","journal-title":"Sci. Diabetes Self Manag. Care"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/pedi.13415","article-title":"Sick day management in children and adolescents with diabetes","volume":"23","author":"Phelan","year":"2022","journal-title":"Pediatr. Diabetes"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2147\/DMSO.S209938","article-title":"Characterization of variable presentations of diabetic ketoacidosis based on blood ketone levels and major society diagnostic criteria: A new view point on the assessment of diabetic ketoacidosis","volume":"12","author":"Lee","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1177\/19322968211042656","article-title":"Continuous ketone monitoring consensus report 2021","volume":"16","author":"Nguyen","year":"2022","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1021\/acs.analchem.9b05109","article-title":"Microneedle-Based Detection of Ketone Bodies along with Glucose and Lactate: Toward Real-Time Continuous Interstitial Fluid Monitoring of Diabetic Ketosis and Ketoacidosis","volume":"92","author":"Teymourian","year":"2020","journal-title":"Anal. Chem."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/1\/110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:31:37Z","timestamp":1759919497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/1\/110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,19]]},"references-count":118,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["children12010110"],"URL":"https:\/\/doi.org\/10.3390\/children12010110","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,19]]}}}