What are the causes of Type I Hyperosmolar Hyperglycemic State (HHS)?

Causes of Type I Hyperosmolar Hyperglycemic State (HHS)

The primary causes of Type I Hyperosmolar Hyperglycemic State (HHS) include infection, inadequate insulin administration, undiagnosed diabetes, and various precipitating factors that lead to severe hyperglycemia without significant ketosis. 1

Pathophysiological Mechanism

• HHS is characterized by a reduction in the net effective action of circulating insulin coupled with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) 1
• Unlike diabetic ketoacidosis (DKA), in HHS there is enough residual insulin to prevent significant lipolysis and ketogenesis, but inadequate amounts to facilitate glucose utilization by insulin-sensitive tissues 1
• The resulting hyperglycemia leads to osmotic diuresis with significant loss of water, sodium, potassium, and other electrolytes 1

Common Precipitating Factors

Infections

• Infection is the most common precipitating factor for HHS in patients with Type 1 diabetes 1, 2
• Patients may present with normal temperature or even hypothermia due to peripheral vasodilation, with hypothermia being a poor prognostic sign 1

Medication-Related Causes

• Medications that affect carbohydrate metabolism can precipitate HHS, including:
  • Corticosteroids 1, 3
  • Thiazide diuretics 1, 3
  • Sympathomimetic agents (e.g., dobutamine, terbutaline) 1
  • Beta-blockers 3
  • Phenytoin 3
  • Diazoxide 3

Insulin-Related Factors

• Discontinuation of insulin therapy in established Type 1 diabetes 1
• Inadequate insulin administration 1
• New-onset Type 1 diabetes that has not yet been diagnosed 1

Other Medical Conditions

• Cerebrovascular accidents 1
• Alcohol abuse 1
• Pancreatitis 1
• Myocardial infarction 1
• Trauma 1
• Severe burns 3
• Parenteral hyperalimentation 3
• Peritoneal dialysis or hemodialysis 3

Vulnerable Populations

• Elderly individuals with newly diagnosed diabetes, particularly residents of chronic care facilities 1
• Individuals with known diabetes who become hyperglycemic but are unaware of it or unable to take fluids when necessary 1

Clinical Presentation

• HHS typically evolves over several days to weeks, unlike DKA which develops more acutely (usually within 24 hours) 1
• Classic symptoms include polyuria, polydipsia, polyphagia, weight loss, dehydration, weakness, and altered mental status progressing to coma 1
• Physical findings include poor skin turgor, tachycardia, hypotension, and altered mental status 1
• Laboratory findings show marked hyperglycemia (typically >600 mg/dl), hyperosmolality (>320 mOsm/kg), minimal or absent ketosis, and absence of significant acidosis 1, 4

Important Clinical Considerations

• HHS carries a higher mortality rate (approximately 15%) compared to DKA (approximately 5%) 1, 5
• The prognosis worsens significantly at the extremes of age and in the presence of coma and hypotension 1
• Rapid changes in osmolality during treatment may precipitate serious complications including cerebral edema and central pontine myelinolysis 5, 6
• Careful monitoring of serum osmolality during treatment is essential, with a recommended reduction rate of 3-8 mOsm/kg/h 5