QTc dispersion, hyperglycemia, and hyperinsulinemia.

and Hyperinsulinemia To the Editor: QTc dispersion is an important predictor of cardiac mortality. In the Rotterdam Study,1 persons in the highest tertile (.60 ms) relative to the lowest tertile (,39 ms) of QTc dispersion had a 2-fold risk of cardiac death. The Rotterdam Study also confirms that QTc dispersion is larger in diabetic than in nondiabetic persons. QTc duration and QTc dispersion are associated with plasma glucose and insulin levels,2 but their relative contributions to each are still unclear. We evaluated the effect of acute hyperglycemia, with or without the accompanying hyperinsulinemia, on QTc duration and QTc dispersion in normal subjects. We studied 27 healthy volunteers (17 men and 15 women) aged 4966 years (mean6SD). All subjects were given a hyperglycemic glucose clamp in which plasma glucose concentrations were acutely raised with a bolus injection of 0.33 g/kg glucose (50% solution) followed by a 30% glucose infusion to achieve steady-state plasma glucose levels of '15 mmol/L for 120 minutes. On another occasion, which was separated from the first by at least a 3-day interval and in random order, the subjects underwent the same hyperglycemic clamp plus octreotide administration (25 mg as IV bolus followed by a 0.5 mg/min infusion) to block the release of endogenous insulin. All tests were made with the aid of an artificial pancreas (Biostator). Electrocardiograms were recorded with a standard resting 12-lead ECG at 50 mm/s. QT interval analysis was done by a cardiologist who was blinded regarding other information. QT intervals were corrected with Bazett’s formula (QTc5QT/R-R); QTc dispersion was calculated as the interlead variability of QTc interval (QTc dispersion5QTcmax2QTcmin). During clamp administration, plasma glucose stabilized at 15 mmol/L, and plasma insulin showed a biphasic pattern of response, with an early rise at 10 minutes (327689 pmol/L) followed by a gradual and sustained increase (4566120 pmol/L). QTc increased from 413626 to 442629 ms (P,0.05) at the end of the clamp administration, and QTc dispersion increased from 3269 to 55612 ms (P,0.01). Basal and clamped plasma glucose levels in the octreotide study were not significantly different from those of the control study; glucose-stimulated insulin responses were markedly reduced by octreotide (105636 pmol/L at 10 minutes and 57616 pmol/L at 120 minutes). QTc and QTc dispersion increases in the octreotide study did not differ from those recorded in the control study. Acute hyperglycemia in normal subjects produces significant increases of QTc and QTc dispersion that persist during octreotide infusion, which suggests a minor role for insulin. Hyperglycemia may induce QT changes by increasing the cytosolic calcium content,3 by stimulating sympathetic activity,4 or both. These results may offer a novel mechanism through which hyperglycemia may add to the elevated cardiovascular risk of the diabetic patient.