Active Ingredient: INSULINE
The relationship between insulin and QT interval depends on the clinical context. Acute insulin administration in euglycemic or hypoglycemic states prolongs the QT interval and may increase arrhythmic risk, particularly in patients with pre-existing prolonged QTc. However, in diabetic patients with metabolic derangements causing baseline QT prolongation, insulin therapy may be protective by correcting the underlying metabolic abnormalities. In a study of 35 healthy volunteers using a euglycemic insulin clamp, QTc (Bazett) increased significantly from 420±5 ms to 428±6 ms. This effect is independent of insulin sensitivity but is directly driven by insulin-induced hypokalemia (potassium levels dropped from 3.76 to 3.44 mM) and adrenergic activation (increase in heart rate and norepinephrine). Baseline QTc was also found to be directly related to fasting plasma insulin levels. Monitoring of potassium levels is essential during insulin therapy to mitigate the risk of QT prolongation. In another prospective study of 119 individuals, acute hypoglycemia (plasma glucose nadir: 1.6±0.5 mmol/L) caused mean QTc to rise from 415.1 ms to 444.9 ms, with abnormal prolongation observed in 26% of males and 17% of females. This effect is associated with a massive surge in plasma epinephrine (from 220 to 2945 pmol/L) and transient hypokalemia (observed in 82% of subjects). While acute hyperinsulinemia can prolong QTc, a study in a Type 1 Diabetes rabbits demonstrates that chronic insulin therapy prevents QT prolongation. Chronic hyperglycemia depresses the HERG channel function (which conducts the IKr current) through two mechanisms: Oxidative stress (ROS production and antioxidant depletion) and downregulation of HERG protein levels. Insulin restores IKr/HERG function and prevents QTc prolongation, partly due to its antioxidant properties.
https://doi.org/10.1152/ajpregu.2000.279.6.r2022, https://doi.org/10.1016/j.diabres.2016.11.021, https://doi.org/10.1152/ajpheart.01356.2005