How is diabetic ketoacidosis classified by severity, complications, and precipitating triggers?

Classification of Diabetic Ketoacidosis

DKA is classified by severity into three categories based on arterial pH, serum bicarbonate, and mental status: mild (pH 7.25–7.30, bicarbonate 15–18 mEq/L, alert), moderate (pH 7.00–7.24, bicarbonate 10–<15 mEq/L, alert/drowsy), and severe (pH <7.00, bicarbonate <10 mEq/L, stupor/coma). 1

Severity-Based Classification

The American Diabetes Association stratifies DKA severity using objective laboratory and clinical parameters that directly guide treatment intensity and monitoring requirements 1, 2:

Mild DKA

• Arterial pH: 7.25–7.30 1
• Serum bicarbonate: 15–18 mEq/L 1
• Anion gap: >10 mEq/L 1, 3
• Mental status: Alert 1
• Plasma glucose: >250 mg/dL 1, 2

Moderate DKA

• Arterial pH: 7.00–7.24 1
• Serum bicarbonate: 10 to <15 mEq/L 1
• Anion gap: >12 mEq/L 1, 3
• Mental status: Alert to drowsy 1
• Plasma glucose: >250 mg/dL 1, 2

Severe DKA

• Arterial pH: <7.00 1, 4
• Serum bicarbonate: <10 mEq/L 1, 4
• Anion gap: >12 mEq/L 1, 3
• Mental status: Stupor or coma 1
• Plasma glucose: >250 mg/dL 1, 2

Critical pitfall: Severe DKA (pH ≤6.9) in type 2 diabetes is more common than previously recognized and does not necessarily carry the ominous prognosis traditionally assumed, though it requires aggressive treatment 4. Hypothermia in any severity category is a poor prognostic sign 1.

Classification by Glycemic Presentation

Classic Hyperglycemic DKA

• Plasma glucose: >250 mg/dL 1, 2
• Represents approximately 90% of DKA presentations 2

Euglycemic DKA (eDKA)

• Plasma glucose: <200–250 mg/dL despite meeting acidosis and ketosis criteria 2, 5, 6
• Accounts for approximately 10% of all DKA cases 2
• Requires: Either documented hyperglycemia at any point OR known diabetes history, PLUS metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L) AND elevated β-hydroxybutyrate 2

Critical pitfall: Euglycemic DKA is easily missed because clinicians may not suspect DKA when glucose is normal or mildly elevated 5, 6. Always measure ketones in diabetic patients with unexplained metabolic acidosis regardless of glucose level 2.

Classification by Precipitating Triggers

The American Diabetes Association identifies specific precipitating factors that should guide both diagnosis and prevention strategies 1:

Infection (Most Common)

• The single most common precipitating factor for both DKA and HHS 1
• Patients may be normothermic or hypothermic due to peripheral vasodilation 1

Insulin-Related Causes

• New-onset type 1 diabetes 1
• Insulin omission or inadequate dosing in established diabetes 1
• Insulin omission is the most common cause in recurrent DKA, often associated with psychiatric illness (especially depression), single-parent homes, and inadequate insurance 1

Medication-Induced

• SGLT2 inhibitors: Most frequent modern cause of euglycemic DKA 2, 5, 6
• Corticosteroids 1
• Thiazide diuretics 1
• Sympathomimetic agents (dobutamine, terbutaline) 1
• Atypical antipsychotics 1

Acute Medical Events

• Myocardial infarction 1
• Cerebrovascular accident 1
• Pancreatitis 1
• Trauma 1

Metabolic/Nutritional Triggers (Especially for eDKA)

• Reduced caloric intake or prolonged fasting 2, 6
• Heavy alcohol consumption 1, 2, 6
• Pregnancy 2, 6
• Chronic liver disease 2, 6

Classification by Complications

Acid-Base Variants

Diabetic ketoalkalosis is an increasingly recognized variant where patients present with pH >7.4 despite significant ketoacidosis 7:

• Accounts for 23.3% of DKA presentations when using β-hydroxybutyrate and anion gap ≥16 mEq/L as diagnostic criteria 7
• Associated with mixed acid-base disorders, most commonly concurrent respiratory alkalosis (81.1% of cases) 7
• Critical pitfall: 34% of diabetic ketoalkalosis cases have severe ketoacidosis (β-hydroxybutyrate ≥3 mmol/L) and require the same aggressive treatment as traditional acidemic DKA 7

Mental Status Alterations

• Alert: Typical in mild DKA 1
• Alert to drowsy: Typical in moderate DKA 1
• Stupor or coma: Typical in severe DKA and more frequent in HHS 1

Gastrointestinal Complications

• Up to 25% of DKA patients have emesis, which may be coffee-ground in appearance and guaiac positive due to hemorrhagic gastritis 1
• Abdominal pain occurs in DKA but not typically in HHS 1

Critical pitfall: Abdominal pain in DKA can be either a result or a cause of the metabolic crisis; further evaluation is necessary if pain does not resolve with correction of dehydration and acidosis 1.

Diagnostic Algorithm for Classification

When evaluating suspected DKA, obtain these specific tests to properly classify severity and guide treatment 2:

1. Plasma glucose (determines hyperglycemic vs. euglycemic presentation) 2
2. Arterial or venous blood gas (pH and bicarbonate for severity classification) 2
3. Serum β-hydroxybutyrate (preferred over nitroprusside-based tests) 2
4. Serum electrolytes with calculated anion gap (>10 mEq/L in mild, >12 mEq/L in moderate/severe) 1, 2, 3
5. Blood urea nitrogen/creatinine (assess renal function and volume status) 2
6. Serum osmolality (distinguish from HHS) 2
7. Complete blood count with differential (evaluate for infection) 2
8. Urinalysis 2
9. Electrocardiogram (assess for myocardial infarction and monitor potassium effects) 2

Critical pitfall: Never use nitroprusside-based urine or serum ketone tests for diagnosis or monitoring, as they only detect acetoacetate and acetone, missing β-hydroxybutyrate (the predominant ketone in DKA), and can falsely suggest worsening ketosis during treatment as β-hydroxybutyrate converts to acetoacetate 2.

Resolution Criteria

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

• Glucose: <200 mg/dL 2
• Serum bicarbonate: ≥18 mEq/L 2, 3
• Venous pH: >7.3 2

Monitor venous pH and anion gap every 2–4 hours during treatment to track resolution 3.