QT prolongation caused by insulin-induced hypoglycaemia - an interventional study in 119 individuals

• Published in: Diabetes research and clinical practice 2017-01, Vol.123, p.165-172
• Main Authors: Kacheva, Stella, Karges, Beate, Göller, Katrin, Marx, Nikolaus, Mischke, Karl, Karges, Wolfram
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac - etiology; Electrocardiography - methods; Endocrinology & Metabolism; Epinephrine; Female; Humans; Hypoglycemia - chemically induced; Insulin, Regular, Human - adverse effects; Insulin-induced hypoglycaemia; Male; Middle Aged; QT dispersion; QTc prolongation; Young Adult
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2016.11.021

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.