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Hyperosmolar Hyperglycemic State (HHS)

Hyperosmolar Hyperglycemic State (HHS) is a life-threatening acute complication of diabetes characterized by severe hyperglycemia, increased plasma osmolality, profound dehydration, and altered mental status, with little or no significant ketoacidosis.

Also called

Hyperosmolar non-ketotic state

ICD-10

E11

Specialty

Endocrine

Onset

Acute

Reviewed

August 2026

On This Page

Overview

  • Hyperosmolar Hyperglycemic State (HHS) usually occurs in patients with Type 2 Diabetes Mellitus, particularly older adults.

 

  • A relative deficiency of insulin causes severe hyperglycemia, while enough insulin is usually present to suppress substantial ketone production.

 

  • Severe hyperglycemia causes osmotic diuresis → profound water and electrolyte loss → increased serum osmolality → neurological dysfunction.

Etiology & Risk Factors

–Etiology:

Hyperosmolar Hyperglycemic State (HHS) develops from:

  • Severe insulin deficiency relative to metabolic needs
  • Increased counter-regulatory hormones
  • Severe hyperglycemia
  • Osmotic diuresis
  • Progressive dehydration
  • Increased serum osmolality

 

–Common precipitating factors include:

  • Infection
  • Pneumonia
  • Urinary tract infection
  • Myocardial infarction
  • Stroke
  • Surgery
  • Trauma
  • Acute illness

 

–Risk Factors

  • Type 2 Diabetes Mellitus
  • Older age
  • Inadequate access to fluids
  • Reduced thirst sensation
  • Cognitive impairment
  • Limited mobility
  • Infection
  • Acute cardiovascular or cerebrovascular disease
  • Poor adherence to diabetes treatment
  • Dehydration
  • Medications that promote hyperglycemia
  • Chronic kidney disease

Pathophysiology

Relative insulin deficiency + increased counter-regulatory hormones → severe hyperglycemia → increased renal glucose excretion → osmotic diuresis → massive water and electrolyte loss → profound dehydration → increased serum osmolality → cellular dehydration → neurological dysfunction → altered consciousness/coma

 

Residual insulin activity → suppression of major lipolysis → limited ketone production → minimal or absent significant ketoacidosis

Clinical Presentation

-Symptoms

  • Polyuria
  • Polydipsia
  • Severe thirst
  • Weakness
  • Fatigue
  • Blurred vision
  • Weight loss
  • Dry mouth
  • Headache
  • Confusion

-Signs:

  • Severe dehydration
  • Dry mucous membranes
  • Poor skin turgor
  • Tachycardia
  • Hypotension
  • Weak peripheral pulses
  • Altered mental status
  • Neurological abnormalities
  • Reduced urine output in severe dehydration

History Taking

-Ask about:

  • Current diabetes medications
  • Medication adherence
  • Recent insulin or medication changes
  • Blood glucose measurements
  • Duration of hyperglycemic symptoms
  • Polyuria
  • Polydipsia
  • Weight loss
  • Reduced oral intake
  • Fluid intake
  • Vomiting or diarrhea
  • Fever
  • Cough
  • Dysuria

Physical Examination

–General Examination

  • Assess:
  • Airway
  • Breathing
  • Circulation
  • Level of consciousness
  • Hydration status
  • Temperature
  • Heart rate
  • Blood pressure
  • Respiratory rate

 

Look for:

  • Severe dehydration
  • Dry mucous membranes
  • Tachycardia
  • Hypotension
  • Altered consciousness

 

System-Specific Examination

 

–Cardiovascular:

  • Tachycardia
  • Hypotension
  • Signs of hypovolemia
  • Signs of myocardial infarction or heart failure

 

–Neurological:

  • Confusion
  • Reduced consciousness
  • Seizures
  • Focal neurological deficits
  • Assessment for stroke

Investigations

-Complete Blood Count

May show:

  • Hemoconcentration due to dehydration
  • Leukocytosis due to physiological stress or infection

A raised White Blood Cell count alone does not prove infection.

 

-Biochemistry / Specific Tests

Essential investigations include:

  • Plasma glucose
  • Serum electrolytes
  • Sodium
  • Potassium
  • Urea
  • Creatinine
  • Serum osmolality or calculated effective osmolality
  • Serum or capillary β-hydroxybutyrate
  • Venous blood gas
  • Bicarbonate
  • Anion gap

 

–Additional investigations:

  • Urinalysis
  • Urine ketones
  • HbA1c
  • Phosphate
  • Lactate when indicated

Diagnosis

-Hyperosmolar Hyperglycemic State (HHS) is diagnosed by demonstrating:

  • Severe hyperglycemia, typically ≥600 mg/dL (33.3 mmol/L)
  • High effective serum osmolality, generally >300 mOsm/kg
  • Severe dehydration
  • Minimal ketonemia
  • No significant ketoacidosis
  • Altered mental status may be present, particularly in severe cases
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Management

1. First-Line / Emergency Management

HHS is a medical emergency requiring hospital treatment.

Initial management:

  • ABC assessment
  • Intravenous fluid resuscitation
  • Careful electrolyte assessment
  • Potassium monitoring
  • Insulin therapy after initial fluid assessment/resuscitation
  • Frequent glucose and osmolality monitoring
  • Identification and treatment of the precipitating cause
  • Thrombosis-risk assessment

2. Definitive Treatment

The fundamental treatment is:

Careful fluid replacement + electrolyte correction + insulin + treatment of the precipitating cause.

Fluid replacement is particularly important because patients may have a very large water deficit.

 

3. Medical Treatment

-Intravenous Fluids

  • Intravenous isotonic crystalloid is generally used initially.
  • Fluid replacement should be individualized according to:
    • Blood pressure
    • Hydration status
    • Serum sodium
    • Renal function
    • Cardiac function
    • Age

-Insulin

  • Intravenous insulin may be used after initial fluid replacement.
  • Insulin lowers plasma glucose and suppresses hepatic glucose production.
  • Glucose should not fall excessively rapidly.

-Potassium

Serum potassium should be monitored frequently.

Total body potassium is often depleted despite variable initial serum potassium levels.

Replacement is guided by:

  • Serum potassium
  • Renal function

Complications

  • Severe dehydration
  • Hypovolemic shock
  • Acute kidney injury
  • Electrolyte abnormalities
  • Hypokalemia
  • Hyperkalemia
  • Cerebral edema
  • Seizures
  • Coma
  • Death

Prognosis

Prognosis depends on:

  • Age
  • Degree of dehydration
  • Severity of hyperosmolality
  • Renal function
  • Cardiovascular status
  • Neurological impairment
  • Presence and severity of infection
  • Time to treatment
  • Underlying precipitating illness

Early recognition and controlled correction of dehydration and hyperosmolality improve outcomes.

Key Points / Clinical Pearls

  • Hyperosmolar Hyperglycemic State (HHS) is a life-threatening diabetic emergency.
  • It occurs most commonly in Type 2 Diabetes Mellitus.
  • HHS is characterized by severe hyperglycemia, hyperosmolality, and profound dehydration.
  • Significant ketoacidosis is usually absent or mild.
  • HHS often develops more gradually than DKA.
  • Older adults are particularly vulnerable.
  • Common triggers include infection, acute cardiovascular disease, stroke, and inadequate diabetes treatment.
  • Neurological manifestations such as confusion, seizures, and coma are important features.
  • Plasma glucose is typically ≥600 mg/dL (33.3 mmol/L).
  • Effective serum osmolality is typically >300 mOsm/kg.
  • Fluid replacement is the cornerstone of initial treatment.
  • Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Diabetes Care. 2024;47(8):1257-1275. Diabetes Care .
  • American Diabetes Association Professional Practice Committee. 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1). Diabetes Care .
  • Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care. 2009;32(7):1335-1343. Diabetes Care .
  • Pasquel FJ, Umpierrez GE. Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment. Diabetes Care. 2014;37(11):3124-3131. Diabetes Care .
  • National Library of Medicine (NIH). Hyperosmolar Hyperglycemic State . StatPearls.