Does insulin cause hypokalemia (low potassium levels)?

From the Guidelines

Insulin can cause hypokalemia, and it is essential to monitor potassium levels closely in patients receiving insulin therapy, especially during intensive treatment for diabetic ketoacidosis or when starting insulin in severely hyperglycemic patients. When insulin is administered, it facilitates the movement of potassium from the bloodstream into cells, particularly muscle cells, which reduces the concentration of potassium in the blood, potentially leading to hypokalemia 1. This effect is most pronounced with intravenous insulin administration, especially at higher doses. The mechanism involves insulin activating the sodium-potassium ATPase pump in cell membranes, which increases potassium uptake into cells.

Key Considerations

• Hypokalemia is common, occurring in about 50% of patients during treatment of hyperglycemic crises, and severe hypokalemia (<2.5 mEq/L) is associated with increased inpatient mortality 1.
• Potassium supplementation may be necessary in patients at risk of developing insulin-induced hypokalemia.
• Symptoms of hypokalemia may include muscle weakness, cardiac arrhythmias, and in severe cases, paralysis.
• Careful monitoring of potassium concentrations is recommended, especially during the initial phase of insulin therapy 1.

Management

• For patients receiving high-dose insulin, a commonly used protocol calls for IV administration of 1 U/kg regular insulin as a bolus, accompanied by 0.5 g/kg dextrose, followed by continuous infusions of 0.5 to 1 U/kg per hour of insulin and 0.5 g/kg per hour of dextrose 1.
• The insulin infusion is titrated as needed to achieve adequate hemodynamic response, whereas the dextrose infusion is titrated to maintain serum glucose concentrations of 100 to 250 mg/dL (5.5 to 14 mmol/L) 1.
• Very frequent serum glucose monitoring (up to every 15 minutes) may be needed during the initial phase of dextrose titration 1.

From the FDA Drug Label

1. 6 Hypokalemia All insulins, including NOVOLOG, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).

Yes, insulin can cause hypokalemia by shifting potassium from the extracellular to intracellular space, and monitoring of potassium levels is recommended in patients at risk for hypokalemia 2.

From the Research

Insulin and Hypokalemia

• Insulin therapy can cause hypokalemia, as evident from a study published in 2013, which found that 81% of patients with diabetic ketoacidosis developed hypokalemia during treatment, with a significant correlation between potassium and sodium excretion 3.
• The development of hypokalemia in patients with diabetic ketoacidosis is associated with increased potassium excretion and insulin treatment, as shown in a study published in 2013 3.
• Insulin stimulates cellular potassium uptake, leading to hypokalemia, and this effect is mediated by the serum and glucocorticoid-inducible kinase SGK1, as demonstrated in a study published in 2009 4.

Pathophysiology of Hypokalemia

• Hypokalemia can occur due to various factors, including hormonal mechanisms involving insulin, β-adrenergic agonists, and aldosterone, which modulate potassium distribution by promoting rapid transfer of potassium across the plasma membrane 5.
• The kidney's distal nephron plays a crucial role in determining final urinary potassium excretion, and alterations in sodium ion delivery to the distal nephron, mineralocorticoid status, or specific inherited or acquired defects in distal nephron function can contribute to hypokalemia 5.

Clinical Evidence

• A case study published in 2016 highlighted the importance of measuring serum potassium levels prior to initiating insulin therapy in diabetic ketoacidosis, as severe hypokalemia can occur prior to treatment 6.
• A review article published in 2022 discussed the prevalence of hypokalemia in diabetic individuals, particularly in those with acute complications such as diabetic ketoacidosis, and emphasized the need for proper management of hypokalemia in these patients 7.