Salbutamol-induced electrophysiological changes show no correlation with electrophysiological changes during hyperinsulinaemic-hypoglycaemic clamp in young people with Type 1 diabetes

P Novodvorsky; A Bernjak; E J Robinson; A Iqbal; I A Macdonald; R M Jacques; J L B Marques; P J Sheridan; S R Heller

doi:10.1111/dme.13650

Salbutamol-induced electrophysiological changes show no correlation with electrophysiological changes during hyperinsulinaemic-hypoglycaemic clamp in young people with Type 1 diabetes

Diabet Med. 2018 Apr 23;35(9):1264-1272. doi: 10.1111/dme.13650. Online ahead of print.

Authors

P Novodvorsky^{1

2}, A Bernjak^{1

3}, E J Robinson^{1

2}, A Iqbal^{1

2

4}, I A Macdonald⁵, R M Jacques⁶, J L B Marques¹, P J Sheridan², S R Heller^{1

2}

Affiliations

¹ Department of Oncology and Metabolism, University of Sheffield.
² Sheffield Teaching Hospitals NHS Foundation Trust.
³ INSIGNEO Institute for in silico Medicine.
⁴ Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield.
⁵ School of Life Sciences, University of Nottingham, Nottingham.
⁶ School of Health and Related Research, University of Sheffield, Sheffield, UK.

Abstract

Aims: Hypoglycaemia causes QT-interval prolongation and appears pro-arrhythmogenic. Salbutamol, a β₂ -adrenoreceptor agonist also causes QT-interval prolongation. We hypothesized that the magnitude of electrophysiological changes induced by salbutamol and hypoglycaemia might relate to each other and that salbutamol could be used as a non-invasive screening tool for predicting an individual's electrophysiological response to hypoglycaemia.

Methods: Eighteen individuals with Type 1 diabetes were administered 2.5 mg of nebulized salbutamol. Participants then underwent a hyperinsulinaemic-hypoglycaemic clamp (2.5 mmol/l for 1 h). During both experiments, heart rate and serum potassium (and catecholamines during the clamp) were measured and a high-resolution electrocardiogram (ECG) was recorded at pre-set time points. Cardiac repolarization was measured by QT-interval duration adjusted for heart rate (QT_c ), T-wave amplitude (T_amp ), T-peak to T-end interval duration (T_p T_end ) and T-wave area symmetry (T_sym ). The maximum changes vs. baseline in both experiments were assessed for their linear dependence.

Results: Salbutamol administration caused QT_c and T_p T_end prolongation and a decrease in T_amp and T_sym . Hypoglycaemia caused increased plasma catecholamines, hypokalaemia, QT_c and T_p T_end prolongation, and a decrease in T_amp and T_sym . No significant correlations were found between maximum changes in QT_c [r = 0.15, 95% confidence interval (95% CI) -0.341 to 0.576; P = 0.553), T_p T_end (r = 0.075, 95% CI -0.406 to 0.524; P = 0.767), T_sym (r = 0.355, 95% CI -0.132 to 0.706; P = 0.149) or T_amp (r = 0.148, 95% CI -0.347 to 0.572; P = 0.558) in either experiment.

Conclusions: Both hypoglycaemia and salbutamol caused pro-arrhythmogenic electrophysiological changes in people with Type 1 diabetes but were not related in any given individual. Salbutamol does not appear useful in assessing an individual's electrophysiological response to hypoglycaemia.