Why is regular insulin (insulin) the preferred choice in the management of diabetic ketoacidosis (DKA)?

From the Guidelines

Regular insulin is the preferred choice in managing diabetic ketoacidosis (DKA) due to its rapid onset of action and predictable pharmacokinetics when administered intravenously, as supported by the most recent guidelines 1. The standard approach involves an initial IV bolus of regular insulin at 0.1 units/kg followed by a continuous infusion at 0.1 units/kg/hour. This regimen allows for quick reduction of blood glucose levels and suppression of ketogenesis, addressing the fundamental metabolic derangements in DKA.

• Regular insulin works by facilitating glucose uptake into cells, inhibiting hepatic glucose production, and suppressing lipolysis and ketone body formation.
• Unlike longer-acting insulin analogs, regular insulin can be titrated easily based on hourly blood glucose measurements, with the goal of decreasing glucose by 50-75 mg/dL per hour.
• The infusion should continue until the anion gap normalizes and ketoacidosis resolves, even after blood glucose falls below 200-250 mg/dL (at which point dextrose should be added to prevent hypoglycemia).
• Regular insulin's short half-life also provides safety, as the effects quickly dissipate if hypoglycemia occurs, making it ideal for the acute management phase of this potentially life-threatening condition, as noted in recent studies 1. Key considerations in the management of DKA include:
• Restoration of circulatory volume and tissue perfusion
• Resolution of hyperglycemia
• Correction of electrolyte imbalance and acidosis
• Treatment of any correctable underlying cause of DKA, such as sepsis, myocardial infarction, or stroke, as emphasized in the latest guidelines 1.

From the FDA Drug Label

Insulin lowers blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Humulin R U-100 is human insulin with a short duration of action. With intravenous use, the pharmacologic effect of Humulin R U-100 begins at approximately 10 to 15 minutes and terminates at a median time of approximately 4 hours (range: 2 to 6 hours) after administration of doses in the range of 0.1 to 0.2 units/kg.

The preferred choice of regular insulin in the management of diabetic ketoacidosis (DKA) is due to its:

• Rapid onset of action: allowing for quick control of blood glucose levels
• Short duration of action: enabling precise control and adjustment of insulin doses
• Intravenous administration: providing a rapid and reliable route of administration in emergency situations, such as DKA 2.

Key benefits of using regular insulin in DKA include:

• Rapid reduction of blood glucose levels
• Inhibition of hepatic glucose production
• Stimulation of peripheral glucose uptake by skeletal muscle and fat
• Correction of the disordered metabolism and inappropriate hyperglycemia of diabetes mellitus 2.

From the Research

Rationale for Using Regular Insulin in DKA

• Regular insulin is often the preferred choice in the management of diabetic ketoacidosis (DKA) due to its short duration of action and low cost 3, 4.
• The use of regular insulin in DKA is supported by studies that have shown its effectiveness in reversing ketoacid production and normalizing blood glucose levels 5, 6.
• Low-dose insulin regimens, which typically use regular insulin, have been found to be as effective as high-dose regimens in treating DKA, with fewer side effects such as hypokalemia and hypoglycemia 6, 4.

Comparison with Insulin Analogues

• Some studies have compared the use of regular insulin with insulin analogues, such as lispro and aspart, in the treatment of DKA 3, 7.
• These studies have found that insulin analogues may be equally effective as regular insulin in treating DKA, but may have a higher cost 3.
• However, the evidence is not conclusive, and more research is needed to determine the optimal insulin regimen for DKA management 7.

Clinical Considerations

• The choice of insulin regimen in DKA should be individualized based on the patient's specific needs and clinical circumstances 5.
• Factors such as the severity of DKA, the patient's renal function, and the presence of other comorbidities should be taken into account when selecting an insulin regimen 5, 4.
• Regular insulin remains a commonly used and effective option for DKA management, particularly in resource-limited settings or when insulin analogues are not available 3, 4.