Hyperosmolar Hyperglycemic State: Symptoms, Types, Causes and Treatment

Hyperosmolar Hyperglycemic State (HHS), also known as Hyperosmolar Hyperglycemic Syndrome (HHS), is a critical, life-threatening complication of diabetes, particularly type 2 diabetes. Characterized by extremely high blood sugar levels, profound dehydration, and increased plasma osmolality, HHS demands immediate medical attention. Despite advances in diabetes care, HHS continues to carry a high risk of morbidity and mortality, particularly among older adults. In this comprehensive guide, we explore the symptoms, types, causes, and treatment of HHS, synthesizing insights from leading clinical research to provide a clear, actionable resource.

Symptoms of Hyperosmolar Hyperglycemic State

Recognizing the symptoms of HHS is crucial for prompt treatment and improved outcomes. Unlike diabetic ketoacidosis (DKA), HHS often develops insidiously over days to weeks, making early detection challenging yet vital.

Main Symptom	Description	Additional Features	Source(s)
Hyperglycemia	Extremely high blood glucose (>600 mg/dL)	May exceed 1,000 mg/dL	1 3 5 10
Dehydration	Dry mucous membranes, poor skin turgor	Tachycardia, hypotension	1 3 5 9 13
Neurologic Signs	Confusion, lethargy, seizures, coma	May progress to coma	1 2 3 5 9
No Ketosis	Minimal or absent ketones	Absence of fruity breath or acidosis	1 3 8 10

Table 1: Key Symptoms

Overview of Key Symptoms

HHS’s presentation is often dramatic but can be easily missed in its early stages. Unlike DKA, which tends to have acute onset and abdominal symptoms, HHS moves more gradually, allowing for severe dehydration and neurologic decline before diagnosis.

Hyperglycemia

• Blood glucose levels in HHS are markedly elevated, typically exceeding 600 mg/dL, and can surpass 1,000 mg/dL in severe cases.
• This profound hyperglycemia results from a combination of insulin deficiency and increased counterregulatory hormones, leading to osmotic diuresis and dehydration 1 3 5 10.

Severe Dehydration

• HHS is characterized by severe, prolonged dehydration, often with signs such as dry mucous membranes, decreased skin turgor, and tachycardia.
• Dehydration is central to the pathophysiology and clinical presentation, with adults losing an average of 9 liters of fluid over 48 hours 1 3 5 13.
• Hypotension may also occur, especially as the condition progresses.

Neurologic Manifestations

• Neurologic symptoms are frequent and range from mild confusion and irritability to seizures and coma.
• The altered mental status results from the hyperosmolarity and profound dehydration impacting cerebral function 2 3 5 9.
• In extreme cases, patients may present unresponsive or in a comatose state.

Absence of Significant Ketosis

• Unlike DKA, patients with HHS have minimal or absent ketone bodies in their blood or urine.
• There is typically no significant metabolic acidosis, and classic signs of ketosis (fruity breath, Kussmaul respirations) are lacking 1 3 8 10.

Types of Hyperosmolar Hyperglycemic State

While HHS is often discussed as a singular entity, variations in its clinical presentation and overlap with other metabolic disturbances have been recognized. Understanding these subtypes is important for tailoring clinical management.

Type	Defining Features	Patient Profile	Source(s)
Traditional HHS	Severe hyperglycemia, hyperosmolarity, no ketosis	Most common in type 2 diabetes	1 5 10
Euglycemic Hyperosmolar	High osmolality, normal/moderate glucose	Older adults, worse prognosis	7
Mixed DKA-HHS	Both ketosis and hyperosmolarity present	Overlap, especially in youth	4 6

Table 2: Types of HHS

Traditional HHS

Traditional HHS is the most recognized form, defined by:

• Plasma glucose >600 mg/dL
• Effective plasma osmolality >320 mOsm/kg
• Absent or minimal ketosis 1 5 10

It predominantly affects elderly patients with type 2 diabetes, often triggered by infection or another acute illness.

Euglycemic Hyperosmolar Hypernatremic State

• A less common but important variant features high plasma osmolality (>320 mOsm/kg) with only moderate or even normal blood glucose levels (≥180 mg/dL).
• This subtype, termed "euglycemic hyperosmolar hypernatremic state," carries an even higher mortality rate (up to 35%) compared to traditional HHS, due in part to severe hypernatremia and older age of affected patients 7.
• Its pathophysiology is similar to traditional HHS, but it is more easily overlooked due to less remarkable hyperglycemia.

Mixed DKA-HHS

• Some patients, especially children and adolescents with type 2 diabetes, may present with features of both DKA (ketosis and acidosis) and HHS (hyperosmolarity and severe dehydration) 4 6.
• This overlap further complicates diagnosis and management, requiring a nuanced approach.

Causes of Hyperosmolar Hyperglycemic State

Identifying the underlying causes of HHS is essential for both treatment and prevention. HHS rarely occurs in isolation; it is usually precipitated by a secondary event or condition.

Cause	Description	Prevalence/Significance	Source(s)
Infection	Pneumonia, UTI, sepsis	Most common precipitant	1 2 3 5 8
Medication Issues	Nonadherence, new drugs (steroids, thiazides)	Frequent cause	1 2 3 5 9
Undiagnosed Diabetes	First manifestation in many cases	Especially in type 2 diabetes	1 2 3 5 8
Coexisting Disease	Stroke, MI, pancreatitis, chronic illness	Increases risk and mortality	2 6 9 10
Social Factors	Limited access to water, poor social support	Elderly and vulnerable patients	2
Substance Abuse	Alcohol or drug use	Less common, but recognized	1 8

Table 3: Common Causes of HHS

Infections

• Infections, especially pneumonia and urinary tract infections, are the leading triggers for HHS 1 2 3 5 8.
• The stress of infection raises counterregulatory hormones, worsening hyperglycemia and dehydration.
• Sepsis can further impair consciousness and complicate management.

Medication-Related Factors

• Nonadherence to insulin or oral hypoglycemic agents is a frequent precipitant.
• Certain medications, such as corticosteroids, thiazide diuretics, antipsychotics, and some immunosuppressants, can worsen hyperglycemia or induce HHS 1 2 3 5 9.
• Restarting medications abruptly after a period of nonuse can also contribute, as highlighted in case reports.

Undiagnosed or Uncontrolled Diabetes

• HHS may be the first presentation of type 2 diabetes, particularly in older adults 1 2 3 5 8.
• Many patients are unaware they have diabetes until they present with this critical complication.

Coexisting Acute or Chronic Disease

• Acute illnesses such as stroke, myocardial infarction, pancreatitis, and other severe stressors can precipitate HHS 2 6 9 10.
• Chronic illnesses leading to limited mobility or inability to access water also increase risk, especially in the elderly.

Social and Behavioral Factors

• Social isolation, cognitive impairment, and lack of access to fluids are important risk factors, particularly in older adults living alone or in care homes 2.
• Substance abuse, while less common, remains a recognized precipitant 1 8.

Treatment of Hyperosmolar Hyperglycemic State

Timely, evidence-based treatment of HHS is critical to reducing its high morbidity and mortality. Management focuses on reversing the underlying pathophysiology while monitoring for complications.

Treatment Step	Description	Key Considerations	Source(s)
Rehydration	IV fluids (0.9% saline, ~9L over 48h in adults)	Monitor for fluid overload	1 3 5 13
Electrolyte Repletion	Potassium, phosphate, magnesium replacement	Start after urine output ensured	1 3 13 14
Insulin Therapy	IV insulin bolus/continuous infusion	Start after partial rehydration	1 3 5 11
Treat Underlying Cause	Antibiotics, withdrawal of offending drugs	Essential for recovery	1 2 3 5 11
Monitoring	Frequent labs, vitals, neurologic status	Watch for complications	1 3 14

Table 4: Core Elements of HHS Treatment

Rehydration

• The first and most critical step is aggressive intravenous fluid replacement.
• Adults typically require about 9 liters of 0.9% saline over 48 hours to correct dehydration 1 3 5 13.
• In children and adolescents, rehydration must be more gradual to avoid cerebral edema 1.

Electrolyte Management

• HHS is associated with significant deficits in potassium, phosphate, and magnesium.
• Potassium replacement should begin once urine output is established, as rapid correction of hyperglycemia and acidosis can cause potentially life-threatening hypokalemia 1 3 13 14.
• Monitor and replace phosphate and magnesium as needed.

Insulin Therapy

• After partial correction of dehydration, intravenous insulin is initiated.
• Typical regimens include an initial bolus (0.1–0.15 units/kg) followed by a continuous infusion (0.1 units/kg/hour), or a continuous infusion without bolus 1 3 5 11.
• The goal is a gradual reduction of blood glucose; rapid reductions can increase the risk of cerebral edema, especially in children.

Treatment of Underlying Causes

• Identifying and managing precipitating factors (such as infection, medication, or acute illness) is essential for full recovery and prevention of recurrence 1 2 3 5 11.
• Withdrawal or adjustment of offending medications, starting antibiotics for infections, or addressing acute medical conditions is mandatory.

Monitoring and Complication Prevention

• Continuous monitoring of glucose, electrolytes, renal function, and vital signs is required throughout treatment 1 3 14.
• Watch for complications such as vascular thrombosis, rhabdomyolysis, and acute renal failure 3 13.
• Transition to subcutaneous insulin and patient education are important to prevent recurrence.

Conclusion

Hyperosmolar Hyperglycemic State is a complex, life-threatening emergency that requires rapid recognition and comprehensive treatment.

Key points covered:

• Symptoms include severe hyperglycemia, dehydration, neurologic changes, and absence of ketosis.
• Types range from traditional HHS to euglycemic and mixed DKA-HHS forms, with varying prognosis and clinical implications.
• Causes are most often infections, medication issues, undiagnosed diabetes, coexisting illnesses, and social vulnerabilities.
• Treatment hinges on aggressive rehydration, careful electrolyte management, insulin therapy, and addressing underlying causes, with vigilant monitoring for complications.

Prompt, evidence-based intervention can dramatically improve outcomes for patients with HHS. Improved awareness, patient education, and targeted prevention strategies remain essential in reducing the burden of this dangerous diabetic emergency.