Diagnostic Criteria and Management of Diabetic Ketoacidosis (DKA)

Essential Diagnostic Criteria

The American Diabetes Association recommends that diabetic ketoacidosis (DKA) can be diagnosed when a patient presents with the triad of hyperglycemia (blood glucose >250 mg/dL), metabolic acidosis (pH <7.3, serum bicarbonate <18 mEq/L), and elevated ketones in blood or urine 1, 2
Blood glucose is typically >250 mg/dL, though euglycemic DKA (glucose <250 mg/dL) can occur, especially with SGLT2 inhibitor use 3
Severe DKA is characterized by an arterial pH of <7.00 1, 2
Serum bicarbonate is <18 mEq/L, with severe DKA having levels <10 mEq/L 1, 4
Ketones are positive in serum and urine 1, 5
Anion gap is >10-12 mEq/L (elevated) 1
Mental status can range from alert to coma depending on severity 1

Essential tests for DKA diagnosis include plasma glucose 3, blood urea nitrogen/creatinine 6, serum ketones (preferably β-hydroxybutyrate) 4, electrolytes with calculated anion gap 6, arterial blood gases 6, urinalysis and urine ketones 6, and complete blood count with differential 6, 7
β-hydroxybutyrate measurement is preferred for diagnosis and monitoring of DKA 5, 8
Nitroprusside-based ketone tests (urine or blood) do not measure β-hydroxybutyrate, the predominant ketone in DKA 5, 8

DKA typically presents with symptoms such as polyuria, polydipsia, polyphagia, weight loss, vomiting, abdominal pain, dehydration, weakness, and altered mental status 1, 4
Physical findings include poor skin turgor, Kussmaul respirations, tachycardia, hypotension, and potentially altered mental status 1
DKA typically evolves rapidly (usually <24 hours) compared to HHS, which develops over days to weeks 1, 2

Euglycemic DKA can occur with SGLT2 inhibitor use 3, pregnancy 5, reduced food intake 3, alcohol use 3, and liver failure 3
Alcoholic ketoacidosis is distinguished by clinical history and glucose levels rarely >250 mg/dL 4
Other causes of high anion gap metabolic acidosis include lactic acidosis, salicylate/methanol/ethylene glycol ingestion 6, 7

Common precipitating factors for DKA include infection 1, new-onset type 1 diabetes 4, insulin omission or inadequate insulin 2, cerebrovascular accident 5, myocardial infarction 5, and drug use (corticosteroids, thiazides, sympathomimetic agents) 6
Alcohol abuse is also a precipitating factor for DKA 5
Pancreatitis is a less common precipitating factor for DKA 4, 7

β-hydroxybutyrate levels should be used to monitor treatment response rather than nitroprusside-based ketone tests 5, 8
Resolution of acidosis or reduction in blood β-hydroxybutyrate is the marker for successful treatment 8

Gastrointestinal symptoms, including nausea, vomiting, and abdominal pain, are common presenting features in patients with euglycemic DKA, with up to 25% experiencing coffee-ground emesis, according to the American Diabetes Association 9
Polyuria, polydipsia, and polyphagia with associated weight loss are frequently reported in patients with euglycemic DKA, as noted by the American Diabetes Association 9
Weakness and malaise are frequently reported in patients with euglycemic DKA, as indicated by the American Diabetes Association 9
Dehydration, manifesting as poor skin turgor, is a common finding in patients with euglycemic DKA, according to the American Diabetes Association 9

Kussmaul respirations, a deep and labored breathing pattern, indicate metabolic acidosis in patients with euglycemic DKA, as noted by the American Diabetes Association 9
Tachycardia and hypotension from volume depletion are common physical examination findings in patients with euglycemic DKA, according to the American Diabetes Association 9
Altered mental status, ranging from full alertness to profound lethargy or coma, may be present in patients with euglycemic DKA, as indicated by the American Diabetes Association 9
Normothermia or hypothermia may be present in patients with euglycemic DKA, even with underlying infection, with hypothermia being a poor prognostic sign, as noted by the American Diabetes Association 9

Blood β‑hydroxybutyrate (β‑OHB) is the gold‑standard test for diagnosing and tracking DKA, superseding nitroprusside‑based urine or serum ketone assays. 10

β‑OHB is the predominant ketone body produced in DKA and contributes the greatest acid load, making its direct measurement essential for accurate assessment of ketosis severity. 10

Nitroprusside dipstick or serum tests detect only acetoacetate and acetone; they completely miss β‑OHB, leading to under‑recognition of true ketosis. 10
As treatment progresses, β‑OHB is enzymatically converted to acetoacetate, causing nitroprusside‑based results to appear falsely elevated and potentially misleading clinicians into thinking ketosis is worsening when it is actually improving. 10

Venous pH values are on average 0.03 units lower than arterial pH and are sufficiently accurate for ongoing monitoring of DKA after the initial diagnosis, eliminating the need for repeated arterial blood gas sampling. 10