QT prolongation caused by insulin-induced hypoglycaemia – An interventional study in 119 individuals. (January 2017) - Kacheva, Stella
Highlights: The scientific approach mimics acute-onset hypoglycaemia in people with diabetes. QTc prolongation affected 26% of the men and 17% of the women. Pre-existing prolonged QTc is associated with risk for ventricular arrhythmias. Abstract: Aims: Hypoglycaemia is associated with increased risk of cardiovascular events and mortality in patients with diabetes, but the extent and mechanisms of this link are ill defined. We here prospectively studied cardiac repolarization abnormalities during insulin-induced hypoglycaemia in humans. Methods: 119 individuals (69 males, age 47.5 ± 13.4 years, range 18–82 years) were assessed during hypoglycaemia after the injection of 0.1–0.25 units/kg human insulin. Corrected QT intervals (QTc) and QT dispersion (QTd) were calculated from serially recorded twelve lead electrocardiograms, and plasma glucose and other endocrine markers were studied. Results: QTc increased from 415.1 ± 21.9 ms (mean ± standard deviation) at baseline to 444.9 ± 26.5 ms during hypoglycaemia (plasma glucose nadir, 1.6 ± 0.5 mmol/L, p = 0.001), accompanied by an increase of QTd from 45.0 ± 22.7 ms to 64.1 ± 40.0 ms ( p < 0.001). Hypoglycaemia-induced abnormal QTc prolongation (defined as ⩾460 ms in females and ⩾450 ms in males) occurred in 17% (9/54) of females and 26% (17/65) of males. 97 of 119 of individuals (82%) developed transient hypokalaemia (K + ⩽3.6 mmol/L), and plasma epinephrine increased from 220.4 ± 169.5 pmol/L at baseline to 2945.6 ± 2421.4 pmol/L during hypoglycaemia. Baseline QTc, but not age or gender, was a significant predictor of hypoglycaemia-induced QTc prolongation ( p = 0.001). Conclusions: Insulin-induced hypoglycaemia frequently causes abnormal QT prolongation and is associated with hypokalaemia and sympathoadrenal activation, thereby increasing the potential risk for ventricular arrhythmias, particularly in individuals with pre-existing high normal QTc.