What are the diagnostic criteria and treatment for Diabetic Ketoacidosis (DKA)?

How to Diagnose Diabetic Ketoacidosis (DKA)

Core Diagnostic Criteria

DKA is diagnosed when all three biochemical criteria are simultaneously present: blood glucose >250 mg/dL, arterial pH <7.30 (or venous pH <7.3), serum bicarbonate <15-18 mEq/L, and positive ketones in blood or urine. 1, 2, 3

The American Diabetes Association requires these specific thresholds 1, 2:

• Hyperglycemia: Blood glucose >250 mg/dL (though this has been de-emphasized due to euglycemic DKA—see below) 2, 3
• Metabolic acidosis: Arterial pH <7.3 AND serum bicarbonate <18 mEq/L 2
• Ketosis: Positive serum or urine ketones 2
• Anion gap: Calculated as [Na⁺] - ([Cl⁻] + [HCO₃⁻]), should be >10-12 mEq/L 1, 3

Critical Laboratory Workup

When DKA is suspected, obtain these tests immediately 2, 3:

Essential initial labs:

• Plasma glucose 2
• Arterial blood gas (pH, bicarbonate) or venous pH 2, 3
• Serum electrolytes with calculated anion gap 2, 3
• Blood urea nitrogen/creatinine 2, 3
• Serum β-hydroxybutyrate (β-OHB) - this is the preferred ketone measurement 2, 3
• Serum osmolality 2, 3
• Complete blood count with differential 2, 3
• Urinalysis 2, 3
• Electrocardiogram 2, 3

Additional tests to consider based on clinical presentation:

• Amylase and lipase (if abdominal pain present) 4
• Hepatic transaminases 4
• Troponin and creatine kinase 4
• Blood and urine cultures (if infection suspected) 4
• Chest radiography 4
• A1C level 4

The Critical Importance of β-Hydroxybutyrate Measurement

The American Diabetes Association strongly recommends measuring blood β-hydroxybutyrate (β-OHB) as the preferred method for diagnosing DKA, NOT nitroprusside-based tests. 2

Here's why this matters clinically 2:

• Nitroprusside methods (urine dipsticks, serum tablets) only detect acetoacetate and acetone, NOT β-OHB 2
• β-OHB is the predominant ketone body in DKA 2
• During treatment, β-OHB converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis when the patient is actually improving 2
• Blood β-OHB accurately reflects both diagnosis and treatment response 2

Severity Classification

DKA severity determines monitoring intensity and prognosis 3:

Mild DKA 2, 3:

• Arterial pH 7.25-7.30
• Serum bicarbonate 15-18 mEq/L
• Anion gap >10 mEq/L
• Mental status: Alert

Moderate DKA 2, 3:

• Arterial pH 7.00-7.24
• Serum bicarbonate 10 to <15 mEq/L
• Anion gap >12 mEq/L
• Mental status: Alert/drowsy

Severe DKA 2, 3:

• Arterial pH <7.00
• Serum bicarbonate <10 mEq/L
• Anion gap >12 mEq/L
• Mental status: Stupor/coma
• Higher morbidity and mortality 3

Euglycemic DKA: A Critical Diagnostic Pitfall

Euglycemic DKA is diagnosed when blood glucose is <200-250 mg/dL but metabolic acidosis, elevated β-hydroxybutyrate, and increased anion gap are present. 2

This variant is increasingly common and easily missed 2, 4:

• SGLT2 inhibitors significantly increase DKA risk and commonly cause euglycemic DKA 2
• Other precipitating factors include pregnancy, heavy alcohol use, cocaine abuse, acute illness, and chronic liver disease 2
• Patients typically have decreased carbohydrate intake with adequate hydration and continued insulin use 5
• If you only check glucose and ignore the biochemical profile, you will miss the diagnosis 5

Clinical Presentation to Look For

Classical symptoms evolve over 24 hours and include 1, 3:

Cardinal symptoms:

• Polyuria, polydipsia, polyphagia 1, 4
• Weight loss 1, 4
• Severe fatigue 4

Gastrointestinal symptoms:

• Nausea and vomiting 1, 4
• Abdominal pain 1, 4
• Up to 25% may have coffee-ground emesis due to hemorrhagic gastritis 3

Physical examination findings:

• Poor skin turgor (dehydration) 1, 3
• Kussmaul respirations (deep, rapid breathing) 3
• Fruity breath odor 3, 6
• Tachycardia and hypotension 3
• Altered mental status ranging from drowsiness to coma 1, 3

Differential Diagnosis

DKA must be distinguished from other causes of high anion gap metabolic acidosis 2, 3:

Alcoholic ketoacidosis (AKA) 2:

• Clinical history of alcohol use
• Glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic
• Less severe acidosis than DKA

Starvation ketosis 2:

• Serum bicarbonate typically not lower than 18 mEq/L
• Less severe acidosis than DKA
• Clinical history of prolonged fasting

Other causes to consider 3:

• Lactic acidosis (measure blood lactate)
• Toxic ingestions (salicylate, methanol, ethylene glycol)
• Chronic renal failure
• Metformin use

Diabetic Ketoalkalosis: An Emerging Recognition

DKA can present with pH >7.4 (diabetic ketoalkalosis) due to mixed acid-base disorders, yet still requires the same aggressive treatment as traditional DKA. 7

This variant accounts for approximately 23% of DKA presentations 7:

• All cases have increased anion gap metabolic acidosis present 7
• Concurrent metabolic alkalosis occurs in 47% and respiratory alkalosis in 81% 7
• 34% have severe ketoacidosis (β-OHB ≥3 mmol/L) despite alkalemic pH 7
• Do not be falsely reassured by normal or elevated pH—check β-OHB and anion gap 7

Resolution Criteria

DKA is considered resolved when ALL of the following are met 1, 2, 3:

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L (if measured) 3

Important caveat: Ketonemia typically takes longer to clear than hyperglycemia, requiring continued monitoring and insulin therapy even after glucose normalizes 3

Monitoring During Treatment

Blood should be drawn every 2-4 hours to measure 1, 3:

• Electrolytes
• Glucose
• Venous pH
• β-hydroxybutyrate
• Anion gap
• BUN and creatinine
• Serum osmolality