The effect of acute hyperglycaemia on QTc duration in healthy man

Abstract

A prolonged heart rate-adjusted QT (corrected QT interval: QTc) is a risk factor for sudden death in patients with the long QT syndrome [1], patients with myocardial infarction [2], subjects referred for Holter monitoring [3] and healthy men and women [4±5]. A prolonged QTc interval has been reported in diabetic patients with autonomic neuropathy [6] and is associated with an increased mortality risk in nephropathic Type I (insulin-dependent) diabetic patients [7], as well as with fasting and post-challenge glucose concentrations in elderly people [8]. Moreover, an association of post-load insulin concentrations with QTc dispersion has been reported in a series of healthy subjects during oral glucose testing [9].A recent epidemiologic study in Type II (non-insulin-dependent) diabetic patients shows that the prevalence of QTc prolongation is as high as 26 % and is associated with heart disease [10].The aims of our study were to evaluate the effect of acute hyperglycaemia on haemodynamic variables, as well as QTc duration and QTc dispersion in normal subjects, and to dissect the effects of hyperglycaemia from those of hyperinsulinaemia by blocking the release of endogenous insulin with octreotide, a somatostatin analogue. AbstractAims/hypothesis. Prolongation of heart rate-adjusted QT (QTc) is associated with an increased risk of coronary heart disease and sudden death. The objective of this study was to investigate whether acute increases of plasma glucose concentrations in healthy subjects could influence QTc and QTc dispersion. Methods. Plasma glucose concentrations were quickly raised to 15 mmol/l in 20 healthy subjects (10 men/ 10 women) and maintained for 2 h. On another occasion, and in random order, all subjects underwent the same hyperglycaemic clamp as above and an infusion of the somatostatin analogue octreotide (25 mg as iv bolus followed by a 0.5 g/min infusion) to block the release of endogenous insulin. Results. Systolic and diastolic blood pressures, heart rate and plasma catecholamine concentrations showed significant increases (p < 0.05) starting after 60 min of hyperglycaemia. QTc, QTc dispersion and PR interval also showed significant increments at 120 min of the hyperglycaemic clamp. The infusion of octreotide did not influence QTc duration, QTc dispersion, PR interval and the haemodynamic effects of acute hyperglycaemia. Conclusion/interpretation. The results show that acute hyperglycaemia produces significant increments of QTc and QTc dispersion in normal subjects. In this context, endogenously released insulin during acute hyperglycaemia seems to play a minor part.

Acute Hyperglycemia Induces Nitrotyrosine Formation and Apoptosis in Perfused Heart From Rat

“…Moreover, intensive insulin treatment during acute myocardial infarction reduces long-term mortality in diabetic patients (9). All this seems consistent with the evidence that an acute increase in plasma glucose levels in normal subjects prolongs the QT interval (10), and that hyperglycemia in acute myocardial infarction can induce such electrophysiological alterations as to favor the occurrence of life-threatening arrhythmias (11).…”

Effect of Stress Hyperglycemia in Acute St Segment Elevation Myocardial Infarction

“…Gokhroo R. et al (41) showed that, in acute myocardial infarction, an increased plasma glucose level have been demonstrated to be capable of inducing, such electro phsyological alterations as to favour the occurrence of arrhythmias, whose outcome could be fatal. This is consistent with the evidence that, an acute increase in blood glucose level in normal subjects produces a significant QT prolongation (42).…”

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease

“…This analysis would suggest that it is chronic hyperglycaemia, rather than the insulin-resistant or hyperlipidaemic aspects of the metabolic syndrome that attenuates autonomic function in Indian Asians. Acute glucose infusion rapidly alters cardiac autonomic function (measured by the QTc on ECG) [30]; in the chronic situation, accumulation of advanced glycation end-products is associated with poorer HRV [31]. In addition, chronic intensive glycaemic control improves cardiac autonomic function [32].…”