Why do patients with diabetic ketoacidosis (DKA) not rapidly decrease to lower blood glucose levels?

From the Guidelines

In diabetic ketoacidosis (DKA), we aim to lower blood glucose gradually rather than rapidly to prevent serious complications, with a recommended reduction rate of approximately 50-75 mg/dL per hour using intravenous insulin, typically at a rate of 0.1 units/kg/hour. This approach is supported by the most recent guidelines, including the 2024 standards of care in diabetes 1. Rapid glucose reduction can cause cerebral edema, particularly in children and young adults, as the brain adapts to high glucose levels by accumulating osmotically active particles. When blood glucose falls too quickly, water moves into brain cells causing swelling. Additionally, rapid correction can trigger hypoglycemia, which may worsen neurological outcomes. Another concern is that correcting glucose too quickly while ketoacidosis persists can lead to a hyperosmolar state.

Key Considerations

• The primary goals in DKA management are to restore fluid balance, correct electrolyte abnormalities (especially potassium, which requires close monitoring), and gradually resolve the acidosis while safely lowering glucose.
• Once glucose reaches approximately 200-250 mg/dL, dextrose should be added to IV fluids while continuing insulin to clear ketones, preventing hypoglycemia while addressing the underlying metabolic derangement.
• The use of bicarbonate in people 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.

Management Approach

• Intravenous insulin is the standard of care for critically ill and mentally obtunded individuals with DKA or HHS.
• Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2–4 h before the intravenous insulin is stopped to prevent recurrence of ketoacidosis and rebound hyperglycemia 1.
• Recent studies have reported that the administration of a low dose of basal insulin analog in addition to intravenous insulin infusion may prevent rebound hyperglycemia without increased risk of hypoglycemia 1.

From the FDA Drug Label

Hypoglycemia is the most common adverse reaction of all insulin therapies, including Humulin R U-100. Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or death The time course of Humulin R U-100 action may vary in different individuals or at different times in the same individual and is dependent on dose, site of injection, blood supply, temperature, and physical activity.

We don't go to lower glucose very fast in DKA because insulin therapy can cause hypoglycemia, which is a serious and potentially life-threatening condition. The time course of insulin action can vary between individuals and is influenced by several factors, making it difficult to predict exactly how quickly glucose levels will decrease. To avoid hypoglycemia, it's essential to monitor glucose levels closely and adjust insulin doses accordingly 2. Key considerations include:

• Dose: The amount of insulin administered
• Site of injection: Where the insulin is injected
• Blood supply: The circulation of blood to the injection site
• Temperature: The body temperature, which can affect insulin absorption
• Physical activity: The level of exercise or physical activity, which can impact glucose levels and insulin requirements

From the Research

Reasons for Not Lowering Glucose Levels Quickly in DKA

• The management of Diabetic Ketoacidosis (DKA) requires a careful approach to avoid complications, as stated in 3, 4, 5, 6, 7.
• Lowering glucose levels too quickly can lead to cerebral edema, a common cause of mortality and morbidity, especially in children with DKA, as mentioned in 4.
• Rapid decreases in effective plasma osmolality early in treatment can also increase the risk of cerebral edema, as discussed in 4.
• Insulin administration should be done cautiously, as it can cause hypokalemia and cardiac arrhythmias in patients with relatively low plasma potassium levels, as suggested in 4.
• The goal of fluid therapy is to lower muscle venous Pco2 to ensure effective removal of hydrogen ions by bicarbonate buffer in muscle and diminish the binding of hydrogen ions to intracellular proteins in vital organs, as explained in 4.

Importance of Gradual Glucose Reduction

• Gradual reduction of glucose levels is crucial to avoid complications and ensure effective management of DKA, as emphasized in 3, 5, 6, 7.
• The treatment of DKA should focus on reversing metabolic derangements, correcting volume depletion, electrolyte imbalances, and acidosis while concurrently treating the precipitating illness, as stated in 6.
• Optimal fluid resuscitation, rate and type of insulin therapy, potassium and bicarbonate replacement are still controversial aspects of DKA management, as discussed in 6.