Diagnostic Criteria for DKA and HHS
Diabetic Ketoacidosis (DKA) Diagnostic Criteria
DKA requires the simultaneous presence of three metabolic abnormalities: hyperglycemia (plasma glucose >250 mg/dL), metabolic acidosis (arterial pH <7.3 AND serum bicarbonate <18 mEq/L), and positive ketones in blood or urine. 1
Core Metabolic Thresholds
- Hyperglycemia: Plasma glucose >250 mg/dL 1
- Metabolic acidosis: Arterial pH <7.3 AND serum bicarbonate <18 mEq/L 1
- Ketosis: Positive serum or urine ketones 1
DKA Severity Stratification
The severity classification is based on the degree of acidosis and mental status 1:
Mild DKA:
Moderate DKA:
Severe DKA:
Critical Laboratory Measurement Considerations
β-hydroxybutyrate (βOHB) measurement in blood is the preferred method for diagnosing DKA, not nitroprusside-based tests. 1 This distinction is crucial because nitroprusside methods (urine dipsticks, serum tablets) only detect acetoacetate and acetone, NOT βOHB, which is the predominant ketone in DKA 1. During treatment, βOHB converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis when the patient is actually improving 1.
Essential Initial Laboratory Workup for DKA
When DKA is suspected, obtain 1:
- Plasma glucose 1
- Arterial blood gas (pH, bicarbonate) or venous pH 1
- Serum electrolytes with calculated anion gap 1
- Blood urea nitrogen/creatinine 1
- Serum βOHB (preferred) or serum/urine ketones 1
- Serum osmolality 1
- Complete blood count with differential 1
- Urinalysis 1
- Electrocardiogram 1
Special Consideration: Euglycemic DKA
SGLT2 inhibitors significantly increase DKA risk and commonly cause euglycemic DKA (glucose <250 mg/dL with ketoacidosis). 1 Euglycemic DKA is diagnosed when blood glucose <200-250 mg/dL, metabolic acidosis is present (pH <7.3, bicarbonate <18 mEq/L), and elevated β-hydroxybutyrate and anion gap are observed 1. Other precipitating factors include pregnancy, heavy alcohol use, cocaine abuse, acute illness, and chronic liver disease 1.
DKA Resolution Criteria
DKA is considered resolved when 1:
Hyperosmolar Hyperglycemic State (HHS) Diagnostic Criteria
HHS is diagnosed when blood glucose is ≥600 mg/dL, effective serum osmolality is ≥320 mOsm/kg H₂O, arterial pH is ≥7.30, serum bicarbonate is ≥15 mEq/L, and ketones are small or absent. 2
Core Metabolic Thresholds
- Hyperglycemia: Blood glucose ≥600 mg/dL 2
- Hyperosmolality: Effective serum osmolality ≥320 mOsm/kg H₂O 2
- Minimal acidosis: Arterial pH ≥7.30 2
- Preserved bicarbonate: Serum bicarbonate ≥15 mEq/L 2
- Minimal ketosis: Small or absent ketones in urine and serum (ketonemia ≤3.0 mmol/L) 2
Critical Calculation for HHS Diagnosis
Effective serum osmolality should be calculated as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18. 2 The threshold for HHS diagnosis is ≥320 mOsm/kg H₂O 2.
Corrected serum sodium for hyperglycemia should be calculated by adding 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL. 2 This correction is essential for accurate diagnosis and management 2.
Clinical Presentation Considerations
Mental status can vary from full alertness to profound lethargy or coma in HHS 2. The absence of altered mental status does not exclude HHS diagnosis when metabolic criteria are met 2. Patients meeting metabolic thresholds (glucose ≥600 mg/dL, osmolality ≥320 mOsm/kg) warrant HHS management regardless of alertness 2. The degree of mental obtundation typically correlates with the severity of hyperosmolarity 2.
Timeline of Development
HHS develops over days to a week, unlike DKA which develops over hours to days 2. This prolonged timeline begins with a precipitating factor (such as infection, stroke, or myocardial infarction) that triggers inadequate insulin action combined with elevated counter-regulatory hormones, leading to progressive hyperglycemia and osmotic diuresis 2.
Essential Initial Laboratory Workup for HHS
When HHS is suspected, obtain 2:
- Plasma glucose 2
- Serum electrolytes with calculated anion gap 2
- Serum osmolality 2
- Blood urea nitrogen and creatinine 2
- Serum ketones (preferably β-hydroxybutyrate) 2
- Arterial blood gases 2
- Complete blood count with differential 2
- Urinalysis with urine ketones by dipstick 2
- Electrocardiogram 2
- HbA1c 2
- Bacterial cultures (blood, urine, throat) if infection is suspected 2
- Chest X-ray if pneumonia is suspected 2
HHS Resolution Criteria
HHS is considered resolved when 2:
- Osmolality <300 mOsm/kg 2
- Hypovolemia is corrected 2
- Cognitive status returns to pre-morbid state 2
- Blood glucose <270 mg/dL 2
Key Distinguishing Features Between DKA and HHS
| Parameter | DKA | HHS |
|---|---|---|
| Glucose | >250 mg/dL [1] | ≥600 mg/dL [2] |
| pH | <7.3 [1] | ≥7.30 [2] |
| Bicarbonate | <18 mEq/L [1] | ≥15 mEq/L [2] |
| Ketones | Positive [1] | Small/absent [2] |
| Osmolality | Variable [1] | ≥320 mOsm/kg [2] |
| Onset | Hours to days [2] | Days to weeks [2] |
| Mortality | <1% [3] | ~15% [2,3] |
Differential Diagnosis Considerations
Alcoholic Ketoacidosis (AKA) vs. DKA
AKA is distinguished by clinical history of alcohol use, with glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic, unlike DKA which characteristically presents with glucose >250 mg/dL. 1, 4 AKA can present with profound acidosis and serum bicarbonate often <18 mEq/L 4.
Starvation Ketosis
Starvation ketosis can be distinguished from both DKA and HHS by mildly elevated glucose (rarely >250 mg/dL) and bicarbonate usually not <18 mEq/L 2, 4. It has less severe acidosis and lower ketone levels than DKA 1.
Common Pitfall
Do not rely solely on nitroprusside-based ketone tests, as they miss β-hydroxybutyrate and can falsely suggest worsening ketosis during treatment when the patient is actually improving. 1 Always measure blood β-hydroxybutyrate when available for accurate diagnosis and monitoring 1.