The consensus report by Umpierrez et al. (1) published in the August 2024 issue of Diabetes Care integrates the American and European diabetes associations’ guidelines on diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in adults. It highlights updates while raising some important questions.
DKA refers to diabetic ketone metabolic acidosis rather than simple acidemia, so distinguishing metabolic acidosis from acidemia is essential. However, DKA diagnostic criteria still rely on parameters of acidemia (pH <7.3 and/or serum bicarbonate <18 mmol/L), with the anion gap omitted. A recent study (2) indicates that pH in DKA can present on a spectrum encompassing acidemia (pH ≤7.3, traditional DKA), mild acidemia (7.3 < pH ≤ 7.4), and alkalemia (pH >7.4, diabetic ketoalkalosis), comprising 49%, 28%, and 23% of cases, respectively. Thus, using pH ≤7.3 alone identifies only about half of potential DKA cases. Even with pH ≤7.3 and/or bicarbonate ≤18 mmol/L, approximately 37% of DKA cases remain undiagnosed. In contrast, an anion gap ≥16 mEq/L identifies 100% of DKA cases, suggesting it is a more sensitive parameter for metabolic acidosis, especially when masked by mixed acid-base disorders. Therefore, including anion gap ≥16 mEq/L along with β-hydroxybutyrate ≥3 mmol/L could reduce missed DKA diagnoses and indicate DKA severity. We support retaining the anion gap as part of the diagnostic criteria of DKA and adjusting it to ≥16 mEq/L (rather than the previous >10 mEq/L) to align with current metabolic acidosis guidelines (3).
For HHS diagnostic criteria, the hyperosmolar criterion has been modified to effective serum osmolality >300 mOsm/kg or calculated total serum osmolality >320 mOsm/kg. When calculating total serum osmolality, the inclusion of alcohol is recommended. Additionally, because measured serum osmolality often exceeds calculated value, measured serum osmolality of >320 mOsm/kg should prompt an HHS diagnosis, even if calculated total serum osmolality is ≤320 mOsm/kg. Thus, we suggest adding measured serum osmolality as an additional criterion for HHS. A recent study (4) describes an HHS variant, termed euglycemic hyperosmolar hypernatremic state, characterized by hyperglycemia (serum glucose ≥180 but <600 mg/dL), hypernatremia (sodium >145 mmol/L), and effective osmolality >320 mOsm/kg. This variant is more prevalent and has higher mortality than traditional HHS, warranting further investigation. Additional questions have also arisen regarding traditional HHS cases with concurrent hypernatremia (5), raising the issue of whether to classify this entity as HHS or hyperosmolar hyperglycemic hypernatremic state. A discussion of these emerging entities may be valuable in future guidelines.
For intravenous fluid treatment, the consensus report recommends 0.9% sodium chloride or other crystalloids and omits 0.45% sodium chloride. Hyperglycemic crises generally involve significant free water deficits due to osmotic diuresis. Many patients appear to have hyponatremia or eunatremia but actually have hypernatremia when sodium is corrected for hyperglycemia. Thus, 0.45% sodium chloride, which is commonly used in practice, should be retained as a therapeutic option.
This consensus report addresses key discrepancies in guidelines for diabetic hyperglycemic crises, clarifying confusions such as Diabetes Canada’s prior statement that “there are no definitive criteria for the diagnosis of DKA.” However, questions regarding diagnostic criteria and fluid management options remain open for further discussion.
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Acknowledgments. During the course of preparing this work, the authors used ChatGPT for the purpose of grammar checkup. Following the use of this tool, the authors formally reviewed the content for its accuracy and edited it as necessary. The authors take full responsibility for the content of this publication.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editor responsible for overseeing the review of the manuscript was John B. Buse.
