Stella Kacheva1, Beate Karges2, Katrin Göller2, Nikolaus Marx3, Karl Mischke3, Wolfram Karges2. 1. Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany. Electronic address: skacheva@ukaachen.de. 2. Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany. 3. Department of Cardiology, Pneumology, Angiology and Internal Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
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±13.4years, range 18-82years) were assessed during hypoglycaemia after the injection of 0.1-0.25units/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±21.9ms (mean±standard deviation) at baseline to 444.9±26.5ms during hypoglycaemia (plasma glucose nadir, 1.6±0.5mmol/L, p=0.001), accompanied by an increase of QTd from 45.0±22.7ms to 64.1±40.0ms (p<0.001). Hypoglycaemia-induced abnormal QTc prolongation (defined as ⩾460ms in females and ⩾450ms 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+ ⩽3.6mmol/L), and plasma epinephrine increased from 220.4±169.5pmol/L at baseline to 2945.6±2421.4pmol/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.
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±13.4years, range 18-82years) were assessed during hypoglycaemia after the injection of 0.1-0.25units/kg humaninsulin. 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±21.9ms (mean±standard deviation) at baseline to 444.9±26.5ms during hypoglycaemia (plasma glucose nadir, 1.6±0.5mmol/L, p=0.001), accompanied by an increase of QTd from 45.0±22.7ms to 64.1±40.0ms (p<0.001). Hypoglycaemia-induced abnormal QTc prolongation (defined as ⩾460ms in females and ⩾450ms 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+ ⩽3.6mmol/L), and plasma epinephrine increased from 220.4±169.5pmol/L at baseline to 2945.6±2421.4pmol/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.
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Authors: Jean-Pierre Valentin; Peter Hoffmann; Catherine Ortemann-Renon; John Koerner; Jennifer Pierson; Gary Gintant; James Willard; Christine Garnett; Matthew Skinner; Hugo M Vargas; Todd Wisialowski; Michael K Pugsley Journal: Toxicol Sci Date: 2022-04-26 Impact factor: 4.109