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

Abstract

Summary. QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group. Thirty-two male diabetic subjects with varying degrees of autonomic dysfunction had repeat QT measurements 3 (range 2-6) years later. QT and QTC lengthened significantly at the second visit, unrelated to age or time between recordings, but which corresponded with changes in autonomic function. Of 71 male diabetic subjects under 60 years followed for 3 years, 13 had died, 8 unexpectedly. Of those with autonomic neuropathy, QT and QTC were significantly longer in those who subsequently died, despite similar ages and duration of diabetes. We conclude that QT/RR interval relationships are altered in diabetic autonomic neuropathy, and that changes in QT length with time parallel changese in autonomic function. There may be an association between QT interval prolongation and the risk of dying unexpectedly in diabetic autonomic neuropathy.Key words: Diabetes mellitus, autonomic neuropathy, QT interval, sudden death, autonomic function tests.Diabetic subjects with clinical features of autonomic neuropathy may die suddenly and unexpectedly, but the mechanisms have not been elucidated [1]. 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.This study was designed to try to throw further light on the possible mechanisms and the relationships between QT interval length and unexpected deaths by addressing three related questions. Firstly, is there good evidence of altered QT interval in diabetic autonomic neuropathy? We have previously shown that in the steady state there are small alterations in QT length associated with autonomic impairment [4]. We wanted to see whether QT/RR interval relationships were also altered in this group. Secondly, does QT interval lengthen with time during the progress of diabetes, and if so is this related to worsening autonomic function? Thirdly, was there a longer QT interval in those diabetic patients who had subsequently died, some suddenly and unexpectedly, when compared with those diabetic subjects who survived? Patients and methods PatientsWe studied different groups in the three parts of the study. By their very nature the studies were retrospective as the QT measurements were taken from 24 h ECG tapes that ha...

Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus

“…In patients with diabetes a prolongation of the QT interval has been associated with autonomic neuropathy [36,37] and a prolonged QTc has been related to an increased risk of sudden death [32,37]. One of our patients may be suspected of having an impaired autonomic nerve function as he had two abnormal tests for parasympathetic neuropathy.…”

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

“…In subjects with type 1 diabetes an increased prevalence of prolonged QT c has been reported before [30,36], in particular in subjects with autonomic neuropathy [36][37][38]. This may indicate that increased QT c relates to diabetic autonomic neuropathy [39].…”

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].…”