The 2024 consensus statement on evaluating and managing hyperglycemic crises in adults that was recently published in Diabetes Care offers several important updates to help practitioners effectively recognize and treat diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (1). Among several new topics discussed in the statement, emphasis is placed on timely diagnosis of DKA. Specifically, updated recommendations state that the diagnosis of DKA should be based on the presence of elevated blood glucose >200 mg/dL or history of diabetes, significant ketonemia, and biochemical evidence of metabolic acidosis, defined as pH <7.3 and/or serum bicarbonate concentration <18 mmol/L. This updated recommendation is significantly different from prior statements in which elevated anion gap >10–12 was part of the diagnostic criteria to establish the presence of metabolic acidosis in DKA (1).
Pure high-anion-gap metabolic acidosis from ketonemia is a classic acid-based disorder in DKA that manifests with reduced pH and serum bicarbonate concentration (2). However, several studies have demonstrated that a considerable number of adults with DKA may present with mixed acid-base disorders. Up to 25–50% of DKA patients may have associated metabolic alkalosis, resulting in the rise of serum bicarbonate concentration to levels >18 mmol/L (3–5). The accompanying metabolic alkalosis in DKA can be acute due to vomiting or as a secondary condition of chronic hyperaldosteronism or hypokalemia and/or chronic use of diuretics. Nonetheless, anion gap in all DKA cases will always remain elevated, which is indicative of ongoing metabolic acidosis, even though bicarbonate level will exceed 18 mmol/L in some scenarios in which individuals present with mixed metabolic acidosis and alkalosis (2). Concomitant mixed acid-base disorders in DKA do not influence unrestrained production of ketones, which is driven by insulinopenia. Hence, laboratory assessment of blood β-hydroxybutyrate concentration or urine ketones will not be affected when associated metabolic alkalosis is present.
If we fully relied only on the new guidance to diagnose metabolic acidosis in DKA in which a decrease in bicarbonate concentration plays a key role, a considerable number of patients whose presentation is accompanied by metabolic alkalosis may experience delay in establishing diagnosis unless the anion gap calculation was performed in early stages of such assessment. Further, from a practical standpoint, the finding of high anion gap will offer critical clues to suggest the presence of DKA during initial biochemical assessment of adults with diabetes presenting with acute illness. The anion gap is easily derived from blood biochemistries. In our opinion, it should be always calculated in individuals with diabetes presenting with acute illness, including those whose bicarbonate level is >18 mmol/L. The combined information from both serum bicarbonate level and anion gap should then prompt providers to assess the state of ketone body formation and pH level, as it is not practically and economically feasible to measure ketones and blood gases in all acutely ill people with diabetes during initial phases of hyperglycemic crisis evaluation. Pending the results of future prospective trials, we believe that finding elevated anion gap >10–12 while assessing all adults suspected to have a hyperglycemic crisis will enhance providers' strategies for timely and cost-effective diagnosis of DKA.
The opinions expressed in this article are those of the author and do not necessarily reflect the views of the U.S. Department of Veterans Affairs.
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Acknowledgments. The author thanks Elvira O. Gosmanova, MD, for helpful comments.
Duality of Interest. A.R.G. serves as an associate editor of BMJ Open Diabetes Research & Care.
Handling Editors. The journal editor responsible for overseeing the review of the manuscript was John B. Buse.
