Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

Abstract

Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN؊ with normal BRS (BRS؉; n ‫؍‬ 10), 2) CAN؊ with impaired BRS (BRS؊; n ‫؍‬ 9), and 3) CAN؉ (n ‫؍‬ 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (؎SE) QTc lengthened from 377 ؎ 9 ms (baseline) to a maximum during hypoglycemia of 439 ؎ 13 ms in BRS؉ subjects and from 378 ؎ 5 to 439 ؎ 10 ms in control subjects. Peak QTc tended to be lower in CAN؉ (baseline, 383 ؎ 6; maximum, 408 ؎ 10) and BRS؊ groups (baseline, 380 ؎ 8; maximum, 421 ؎ 11; F ‫؍‬ 1.7, P ‫؍‬ 0.18). Peak epinephrine concentrations (nmol/l) were 3.1 ؎ 0.8 (BRS؉), 2.6 ؎ 0.5 (BRS؊), 1.4 ؎ 0.3 (CAN؉), and 5.7 ؎ 0.8 (control subjects). These data do not indicate that those with CAN are at particular risk for abnormal cardiac repolarization during hypoglycemia. Indeed, they suggest that such patients may be relatively protected, perhaps as a result of attenuated sympatho-adrenal responses. Diabetes 53: [1535][1536][1537][1538][1539][1540][1541][1542] 2004

Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes

“…Experimental protocol We studied participants who had shown QTc lengthening during previous experimental hypoglycaemia [2]. They were invited to undergo a similar hypoglycaemic clamp at least 4 weeks later; before this second visit, subjects took atenolol 100 mg daily for 7 days up to and including the study day.…”

“…Adrenaline (epinephrine) infusion causes QTc lengthening [6], and similar changes during hypoglycaemia are associated with sympathoadrenal activation [2,4]. We have previously shown that short-term administration of the selective β 1 -adrenergic blocking agent atenolol largely prevents hypoglycaemic QTc lengthening in non-diabetic subjects [4].…”

“…We have previously reported lengthening of rate-corrected QT (QTc) interval on the ECG during experimental [2] and clinical [3] hypoglycaemia in type 1 diabetic subjects, and proposed hypoglycaemia as a cause of the acquired long QT syndrome [4]. Since QTc prolongation predicts ventricular arrhythmias [4], we have proposed this as a mechanism of mortality [5].…”

Risk of Cardiac Arrhythmias During Hypoglycemia in Patients With Type 2 Diabetes and Cardiovascular Risk

“…Previous studies have reported inconsistent effects of acute experimental hypoglycemia on cardiac autonomic activity (12,13). We have previously shown that cardiac autonomic neuropathy (CAN) may modify the relationship between hypoglycemia and cardiac repolarization (14).…”

Diabetes Control and Hypoglycemia

“…The QT interval is increased more in those with diabetic autonomic neuropathy. It is well documented that an increased QT interval can lead to ventricular fibrillation and sudden death (Lee, 2004). …”