Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

Abstract

SUMMARY Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autono.mic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval.The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy.An association between an abnormal QT interval and sudden cardiac death has been found in various diseases.'2 The influence of autonomic tone on the QT period is also widely accepted, although the mechanisms underlying the shortening or lengthening of this period are still not clear."4In the late 1970s several reports noted the high incidence of sudden death in diabetic patients who had severe autonomc neuropathy."6 In some cases death was attributed to cardiorespiratory arrest, but in the overwhelming majority the cause of death was not identified.This prompted us to investigate changes in QT interval during static (quiet lying, sitting, and standing) and dynamic (Valsalva manoeuvre) conditions in groups of diabetic patients with different degrees of autonomic neuropathy. Patients and methodsThe diabetic patients (men aged (mean (SD)) 42 (12)

Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients

“…In diabetes, where sudden and unexpected deaths also occur, a similar mechanism has been proposed [2,3,6]. However, although QT interval prolongation has been reported by several groups [2][3][4][5][6], including our own [4], no group has yet produced anything more than tentative suggestions linking prolonged QT intervals and sudden death in these patients. Neither has there been any convincing explanation put forward of the possible mechanisms that might give rise to QT prolongation in individuals with diabetes.…”

“…A similar argument has been put forward to explain some of the deaths associated with the 'sudden infant death syndrome', with uneven development of the right and left sided sympathetic supply to the heart in the first six months of life, leading to a similar electrical instability with potentially fatal arrhythmias [7]. In diabetes, where sudden and unexpected deaths also occur, a similar mechanism has been proposed [2,3,6]. However, although QT interval prolongation has been reported by several groups [2][3][4][5][6], including our own [4], no group has yet produced anything more than tentative suggestions linking prolonged QT intervals and sudden death in these patients.…”

“…There has been considerable recent interest in the relationship between QT interval length, diabetes mellitus and sudden death, with evidence to suggest that where diabetic autonomic neuropathy co-exists the QT interval is prolonged [2][3][4][5][6]. It has been speculated that this could provide a possible explanation for the unexpected deaths [2,3,6], based on observations of the long QT syndrome and the sudden infant death syndrome [7]. To date, however, no firm evidence has been produced directly linking QT interval lengthening and sudden deaths in diabetic subjects.…”

Diabetes and the occurrence of ventricular arrhythmic events in patients with severe left ventricular dysfunction

“…The association between diabetes and sudden death seems to be highest in patients with diabetic autonomic neuropathy [13,14,15,16]. These observations have led to the suggestion that ventricular arrhythmias are the mechanism of unexplained death in diabetic patients and that autonomic neuropathy increases the risk for arrhythmic events [17,18,19,20,21].…”

“…Predisposition to ventricular arrhythmias has been proposed based on the association of diabetic autonomic neuropathy and QT prolongation [19,21]. The observation that diabetic autonomic neuropathy is associated with a substantial diminution of parasympathetic tone led to the hypothesis that relative predomi- Table 2 nance of sympathetic activity might predispose patients with diabetes to arrhythmias [17,18].…”