Foussas et al. (1) observed that in type 2 diabetic patients intensive insulin treatment during acute coronary syndrome was associated with decreased QT dispersion, while the heart rate–corrected QT (QTc) interval tended to increase. This may be of concern because QTc prolongation is known to increase the risk of ventricular arrhythmia and sudden death. However, prognosis of diabetic patients with acute myocardial infarction can be improved by treatment of hyperglycemia with insulin (2).
Apart from myocardial ischemia and infarction, different factors in diabetic patients contribute to the duration of QTc interval, such as insulin resistance, glucose tolerance, glycemic control, and diabetes complications (3–5). Thus, QTc prolongation in the diabetic heart is likely of multifactorial origin. The results of Foussas et al. suggest that hyperinsulinemia related to insulin treatment may also contribute to myocardial repolarization. We have conducted a study that deals with insulin-induced QTc prolongation and focuses on the associations between QTc and acute and chronic hyperinsulinemia in nondiabetic subjects.
We studied 35 nondiabetic offspring of type 2 diabetic patients with a wide range of insulin sensitivity and fasting plasma insulin concentration and 19 control subjects as described in detail elsewhere (6). Acute hyperinsulinemia was produced with the euglycemic-hyperinsulinemic clamp technique. Plasma insulin was raised to the desired level, where it was maintained by a continuous insulin infusion at a rate of 480 pmol · m body surface area−2 · min−1. Blood glucose was clamped at 5.0 mmol/l by infusing glucose at varying rates. Average QT and QTc (QT/R-R interval−0.5) intervals were assessed from 30-min electrocardiogram recordings at baseline and at steady state during the clamp by using a computerized method.
We found that QT and QTc intervals were comparable in subjects with and without family history of type 2 diabetes. Compared with men, women had longer QT (415 ± 7 vs. 389 ± 6 ms, P < 0.01) and QTc intervals (425 ± 5 vs. 400 ± 5 ms, P < 0.001). After adjustment for sex, QTc interval correlated with the rates of whole-body glucose uptake (r = −0.32, P < 0.05) and with fasting plasma insulin concentration (r = 0.33, P < 0.05). During acute hyperinsulinemia, heartbeat interval decreased significantly (956 ± 18 to 894 ± 15 ms, P < 0.001) and QT interval remained unchanged (404 ± 5 vs. 406 ± 5 ms, NS), whereas QTc interval increased (414 ± 4 to 430 ± 4 ms, P < 0.001).
Our findings suggest that repolarization of the myocardium is also influenced by acute hyperinsulinemia in nondiabetic subjects. Thus, this phenomenon is not restricted to the diabetic heart. Although significant change in QTc interval was observed in response to acute hyperinsulinemia, there were also relations between QTc interval and fasting plasma insulin concentration and insulin sensitivity, suggesting that insulin contributes to myocardial repolarization in physiological conditions. These interrelations highlight the diverse effects of insulin on the cardiovascular system.
