Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization

Robinson, R.; Harris, Nigel; Ireland, R.H.; Lindholm, Anders; Heller, Simon

doi:10.1046/j.1365-2125.2003.01726.x

Cited by 31 publications

(29 citation statements)

References 35 publications

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“…We observed a strong relationship between the increase in epinephrine and the increase in QTc and a weaker relationship between the decrease in plasma potassium and QT (5). We then showed a consistent increase in QTc during hypoglycemia in nondiabetic subjects and also recorded increased QT dispersion, another measure of cardiac repolarization (8).…”

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confidence: 58%

Mechanisms of Abnormal Cardiac Repolarization During Insulin-Induced Hypoglycemia

et al. 2003

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Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without ␤-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without ␤-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P ‫؍‬ 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during potassium replacement (46 ms, P ‫؍‬ 0.02). In study 2, the increase in QTd during hypoglycemia (68 ms, P < 0.0001) was prevented by ␤-blockade (3 ms, P ‫؍‬ 0.88). The increase in QTc during hypoglycemia (55 ms, P < 0.0001) was prevented by ␤-blockade (1 ms, P ‫؍‬ 0.98). Our data indicate that hypoglycemia causes an acquired long QT syndrome. Sympathoadrenal stimulation is the main cause, through mechanisms that involve but are not limited to catecholamine-mediated hypokalemia. These abnormalities are prevented by selective ␤-blockade. Diabetes

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confidence: 58%

Mechanisms of Abnormal Cardiac Repolarization During Insulin-Induced Hypoglycemia

et al. 2003

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“…The critical QT period which confers particular vulnerability to VT probably varies for different individuals but is considered to be around 550 ms [3]. We have previously shown that experimental hypoglycaemia is an acquired cause of abnormal cardiac repolarization with some individuals experiencing corrected QT intervals up to 580 ms [4,5]. Our data indicate that these abnormalities are caused by activation of the sympathoadrenal system since they can largely be prevented by beta blockade [6].…”

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confidence: 75%

Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes

et al. 2004

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Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. Methods. We studied 22 patients with Type 1 diabetes (mean age 40.4±17.2 years, duration of diabetes 17.2±9.3 years, HbA1c 8.2±1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. Results. Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (±15) above baseline, compared with 9 ms (±19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (±0.21) above baseline during hypoglycaemia, compared with −0.05 nmol/l (±0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. Conclusion/interpretation. QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia. [Diabetologia (2004) 47:312-315]

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“…The changes in TCRT tended to be even more evident in the diabetic patients than those occurring in their healthy counterparts. The changes in TCRT were not associated with changes in the autonomic regulation of heart rate, sympatho-adrenal activation or changes in the potassium level, suggesting that hypoglycaemia as such also exerts an influence on cardiac repolarisation patterns by other In several previous studies [3][4][5][6][7][8][9], a prolonged QT c interval and an increased QT dispersion have been reported during hypoglycaemia. According to earlier studies [10], the most often used formula, i.e.…”

Section: Discussionmentioning

confidence: 97%

“…Observational and experimental studies have demonstrated that hypoglycaemia results in a prolonged QT interval and an increased QT dispersion in healthy individuals and in patients with type 1 and type 2 diabetes [3][4][5][6][7][8][9]. This may partly explain the proarrhythmic effects of hypoglycaemia.…”

Section: Introductionmentioning

confidence: 98%

Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes

et al. 2007

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Aims/hypothesis Nocturnal hypoglycaemia may contribute to sudden death in diabetic patients. However, it is not well known why hypoglycaemia makes these patients prone to death. Methods We assessed the effects of controlled hypoglycaemia on cardiac repolarisation using novel electrocardiographic descriptors of T-wave and QRS complex morphology in 16 type 1 diabetic patients and eight healthy counterparts. Several electrocardiographic variables characterising repolarisation were analysed from digitised 12-lead electrocardiograms during a euglycaemic and a hypoglycaemic clamp. Results Hypoglycaemia did not result in significant changes either in the QT interval corrected for heart rate by the nomogram method or in QT dispersion. However, the morphology of the T-wave changed significantly during hypoglycaemia. The T-wave amplitude and area in precordial leads decreased significantly in both groups (p<0.05 to p<0.001). The spatial QRS-T angle (total cosine R to T) (p<0.05) and the height and the width of the T-wave loop (p<0.05 and p<0.01, respectively) were also reduced in the diabetic patients. The changes in the repolarisation parameters did not exhibit any significant association with changes in catecholamine levels or in heart rate variability in either group. Conclusions/interpretation Hypoglycaemia results in distinct alterations in cardiac repolarisation, which may increase the vulnerability to arrhythmic events.

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Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization

Cited by 31 publications

References 35 publications

Mechanisms of Abnormal Cardiac Repolarization During Insulin-Induced Hypoglycemia

Mechanisms of Abnormal Cardiac Repolarization During Insulin-Induced Hypoglycemia

Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes

Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes

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