Hyperosmolar hyperglycemic state

Definition

Hyperosmolar hyperglycemic state (HHS) is an acute metabolic decompensation with marked hyperglycemia, extreme dehydration, plasma hyperosmolality and impaired consciousness, without relevant ketoacidosis. Former terms are hyperosmolar (non-ketotic) coma or HHNK.

Occurrence & epidemiology

HHS is mainly a complication of type 2 diabetes and often occurs in the setting of acute physiological stress. It may be the first manifestation of previously unknown type 2 diabetes. Mixed pictures of HHS and DKA are not uncommon.

Aetiopathogenesis

The remaining insulin secretion is sufficient to largely suppress ketogenesis, but not hyperglycemia. Because symptoms of acidosis are absent, the phase of osmotic diuresis usually lasts longer than in DKA. If the fluid loss is not matched by drinking, severe dehydration and very high glucose and osmolality values develop. The fluid deficit can exceed 10 liters.

Precipitating factors:

• acute infections and other acute illnesses
• inadequate fluid intake during osmotic diuresis
• drug-induced, e.g. glucocorticoid-induced or caused by medicines that increase fluid loss
• poorly controlled or previously undiagnosed diabetes

Clinical features

HHS usually develops after a prolonged phase of symptomatic hyperglycemia with osmotic diuresis.

• impaired consciousness as the leading symptom, ranging from confusion and disorientation to coma
• extreme dehydration
• unlike DKA, focal or generalized seizures and transient hemiparesis

Complications: circulatory collapse, thrombosis, disseminated intravascular coagulation, aspiration pneumonia, acute kidney injury and ARDS.

Diagnosis

Diagnostic criteria

• plasma glucose ≥ 600 mg/dl (≥ 33.3 mmol/l)
• serum osmolality > 300 mosmol/kg; it is typically above 320 mosmol/kg
• no relevant ketosis
• no acidosis: pH ≥ 7.3 and bicarbonate ≥ 15 mmol/l

Further findings

• urea and creatinine markedly raised (prerenal kidney failure)
• sodium low or high depending on volume loss; hyperglycemia lowers the measured value by dilution
• potassium usually normal
• pH usually above 7.3; occasionally mild lactic acidosis
• urine for ketone bodies; search for the precipitating factor (e.g. infection)
• A markedly elevated capillary glucose during the work-up of impaired consciousness often leads to the diagnosis.

HHS and DKA compared

• DKA: glucose > 200–250 mg/dl (11.1–13.8 mmol/l) or known diabetes; pH < 7.30, bicarbonate < 15–18 mmol/l, increased anion gap; ketone bodies in serum or urine.
• HHS: glucose ≥ 600 mg/dl (≥ 33.3 mmol/l); serum osmolality > 300 mosmol/kg; no relevant ketosis (urine ketones < 2+ or beta-hydroxybutyrate < 3.0 mmol/l); pH ≥ 7.3 and bicarbonate ≥ 15 mmol/l.
• Consciousness: in HHS, impaired consciousness is the leading symptom; in DKA, lethargy and somnolence occur with severe decompensation.
• Mixed forms: overlap between DKA and HHS has been described in more than one third of hyperglycemic crises.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Acute Complications of Diabetes Mellitus
2. Umpierrez et al.: Hyperglycemic Crises in Adults With Diabetes – A Consensus Report (Diabetes Care 2024)
3. MSD Manual Professional: Type 2 Diabetes Mellitus

Cross-references