From the Guidelines
Hyperosmolar states are primarily caused by severe dehydration combined with hyperglycemia, with the two main conditions being hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA), as noted in the most recent guidelines 1.
Causes of Hyperosmolar States
The causes of hyperosmolar states can be multifactorial, including:
- Infections, such as urinary tract infections and pneumonia
- Medications, including glucocorticoids, thiazide diuretics, and sympathomimetics
- Non-compliance with diabetes medications
- Undiagnosed diabetes
- Stroke, myocardial infarction, pancreatitis, and alcohol abuse These factors can lead to profound insulin deficiency, coupled with inadequate fluid intake, resulting in HHS, typically in type 2 diabetes patients 1.
Pathophysiology
Physiologically, insufficient insulin leads to uncontrolled hepatic glucose production and decreased peripheral glucose utilization, resulting in hyperglycemia, as discussed in recent reviews 1. This causes osmotic diuresis, leading to dehydration and electrolyte imbalances. As dehydration worsens, kidney function declines, preventing glucose excretion and creating a vicious cycle of worsening hyperglycemia and hyperosmolarity.
Treatment
Treatment requires aggressive fluid resuscitation with normal saline, insulin therapy, and careful electrolyte monitoring and replacement, particularly potassium, as levels may drop precipitously with insulin administration, as recommended in the latest guidelines 1.
Key Considerations
In elderly patients, diminished thirst sensation can exacerbate dehydration, highlighting the need for careful monitoring and management of fluid status 1. Additionally, the use of bicarbonate in patients with DKA has been shown to make no difference in the resolution of acidosis or time to discharge, and its use is generally not recommended 1.
From the FDA Drug Label
Hyperglycemia, diabetic ketoacidosis, or hyperosmolar coma may develop if the patient takes less Humulin R U-100 than needed to control blood glucose levels This could be due to increases in insulin demand during illness or infection, neglect of diet, omission or improper administration of prescribed insulin doses or use of drugs that affect glucose metabolism or insulin sensitivity.
The cause of hyperosmolar states includes:
- Increases in insulin demand during illness or infection
- Neglect of diet
- Omission or improper administration of prescribed insulin doses
- Use of drugs that affect glucose metabolism or insulin sensitivity 2
Note that hyperosmolar non-ketotic syndrome can also be caused by severe sustained hyperglycemia 2, 2.
From the Research
Causes of Hyperosmolar States
- Hyperosmolar hyperglycemic state is a life-threatening emergency that can be caused by various factors, including underlying infections, certain medications, nonadherence to therapy, undiagnosed diabetes mellitus, substance abuse, and coexisting disease 3
- In children and adolescents, hyperosmolar hyperglycemic state is often present when type 2 diabetes is diagnosed 3
- Serious cardiovascular disease, acute stroke, genitourinary and/or respiratory infections, and conditions preventing adequate water intake during osmotic diuresis are also common causes of hyperosmolar hyperglycemic state 4
- Other causes include inappropriate medication therapy, social conditions, and it is often the first manifestation of type 2 diabetes 4
Precipitating Factors
- Underlying infections are the most common precipitating cause of hyperosmolar hyperglycemic state 3
- Certain medications, such as those that increase glucose levels or reduce insulin sensitivity, can also precipitate hyperosmolar hyperglycemic state 3
- Nonadherence to therapy, including not taking insulin or oral medications as prescribed, can also lead to hyperosmolar hyperglycemic state 3
- Substance abuse, such as alcohol or drug use, can also precipitate hyperosmolar hyperglycemic state 3
Pathogenesis
- Hyperosmolar hyperglycemic state is characterized by extreme hyperglycemia, severe dehydration, and plasma hyperosmolarity, with minimal or absent ketoacidosis 4
- The pathogenesis of hyperosmolar hyperglycemic state is not fully understood, but it is thought to involve a combination of factors, including insulin deficiency, glucose toxicity, and dehydration 4
- The regulatory mechanisms underlying water and sodium metabolism play a crucial role in the development of hyperosmolar disorders, including hyperosmolar hyperglycemic state 5