Differentiating Hyperosmolar Hyperglycemic State (HHS) from Diabetic Ketoacidosis (DKA)

Laboratory Diagnostic Criteria (American Diabetes Association)

DKA is defined by plasma glucose ≥ 250 mg/dL, arterial pH < 7.30 (often 7.25–7.30 in mild cases), serum bicarbonate < 18 mEq/L, and strongly positive urine/serum ketones; an anion gap is typically ≥10–12 mEq/L, while serum osmolality is variable. 1
HHS is defined by plasma glucose ≥ 600 mg/dL, arterial pH > 7.30, serum bicarbonate ≥ 15 mEq/L, minimal or absent ketones, effective serum osmolality ≥ 320 mOsm/kg, and a variable anion gap. 1

DKA develops rapidly, with metabolic derangements usually occurring within 24 hours. 2
HHS evolves more slowly, often over several days to weeks. 2

DKA‑specific signs:
- Kussmaul respirations (deep, rapid breathing) indicate metabolic acidosis. 2
- Abdominal pain and vomiting occur in up to ~25 % of patients. 2
- Fruity breath odor from acetone is a classic manifestation. 1
HHS‑specific signs:
- Altered mental status ranging from confusion to stupor/coma is more frequent and severe than in DKA. 1, 2
Findings common to both conditions:
- Poor skin turgor, tachycardia, and hypotension. 2
- Polyuria, polydipsia, weight loss, and generalized weakness. 2
- Patients may be normothermic or hypothermic; hypothermia signals a poorer prognosis. 2

HHS occurs when residual insulin is sufficient to suppress lipolysis and ketogenesis but inadequate for effective glucose utilization; DKA results from profound insulin deficiency permitting unchecked lipolysis and ketone production. 1
The mechanistic explanation for HHS is supported by weak evidence. 1

Mental status alone should not be used to differentiate the two entities; coma can occur in both DKA and HHS. 1, 2
Effective serum osmolality must be calculated correctly using the formula:
A glucose level > 600 mg/dL does not automatically indicate HHS; significant ketonemia still points toward DKA. 1

In adults presenting with an acute hyperglycemic emergency, a plasma glucose ≥ 250 mg/dL supports a diagnosis of DKA. 3
For DKA, a serum bicarbonate < 18 mEq/L (often < 15 mEq/L in moderate‑to‑severe cases) is a key laboratory criterion. 3
In the same clinical context, a plasma glucose ≥ 600 mg/dL defines HHS. 3
HHS is characterized by a serum bicarbonate ≥ 15 mEq/L, indicating relative preservation of acid‑base status. 3

β‑hydroxybutyrate is the predominant ketone body in DKA; direct measurement is recommended for accurate assessment of ketosis. 3
Nitroprusside‑based assays detect only acetoacetate and acetone and may falsely suggest worsening ketosis during treatment as β‑hydroxybutyrate converts to acetoacetate. 3

DKA resolution is considered achieved when plasma glucose falls below 200 mg/dL. 3
Resolution also requires serum bicarbonate to rise to ≥ 18 mEq/L. 3
Additionally, a venous pH ≥ 7.3 indicates metabolic recovery. 3