What is the differential diagnosis for a patient with a high anion gap of 22 mmol/L in the Emergency Department (ED)?

Diabetic Ketoacidosis (DKA)

For a patient presenting to the ED with an anion gap of 22 mmol/L, diabetic ketoacidosis is the most likely diagnosis and should be your primary consideration. 1, 2

Top 3 Questions to Ask

• "Do you have diabetes, and if so, have you been taking your insulin as prescribed?" - New-onset type 1 diabetes or discontinuation/inadequate insulin in established diabetes are the most common precipitating factors for DKA. 1

• "Have you had any recent infections, fever, or symptoms of illness?" - Infection is the most common precipitating factor for DKA, though patients may be normothermic or even hypothermic due to peripheral vasodilation. 1, 2

• "Have you been eating normally, or have you been vomiting or unable to keep food down?" - This helps distinguish DKA from other causes of ketoacidosis like starvation ketosis (which rarely has glucose >250 mg/dL and bicarbonate usually not <18 mEq/L) or alcoholic ketoacidosis (which typically presents with mildly elevated or even low glucose). 1

Top Priority Physical Exam

Your priority physical exam should focus on assessing volume status and mental status. 1

• Evaluate hydration status by checking mucous membranes, skin turgor, capillary refill, and orthostatic vital signs - DKA causes profound dehydration requiring aggressive fluid resuscitation at 15-20 mL/kg/hour initially. 1, 3

• Assess mental status carefully - altered consciousness ranging from full alertness to profound lethargy or coma can occur, with the degree of obtundation helping gauge severity. 1

• Check for Kussmaul respirations (deep, rapid breathing) - this compensatory respiratory pattern indicates significant metabolic acidosis. 1

• Look for signs of infection as a precipitating cause, though remember that hypothermia (if present) is a poor prognostic sign rather than fever being required. 1

Critical Diagnostic Pitfall

Do not assume all ketoacidosis is DKA. An anion gap of 22 mmol/L with ketones could also represent alcoholic ketoacidosis or starvation ketosis, which are distinguished by plasma glucose levels - DKA requires glucose ≥250 mg/dL, while these other conditions typically have mildly elevated or even low glucose. 1, 2 Additionally, euglycemic DKA (glucose <200 mg/dL) is increasingly recognized, particularly in patients on SGLT-2 inhibitors. 4