Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without ␤-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without ␤-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P ‫؍‬ 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during potassium replacement (46 ms, P ‫؍‬ 0.02). In study 2, the increase in QTd during hypoglycemia (68 ms, P < 0.0001) was prevented by ␤-blockade (3 ms, P ‫؍‬ 0.88). The increase in QTc during hypoglycemia (55 ms, P < 0.0001) was prevented by ␤-blockade (1 ms, P ‫؍‬ 0.98). Our data indicate that hypoglycemia causes an acquired long QT syndrome. Sympathoadrenal stimulation is the main cause, through mechanisms that involve but are not limited to catecholamine-mediated hypokalemia. These abnormalities are prevented by selective ␤-blockade. Diabetes

Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. Methods. We studied 22 patients with Type 1 diabetes (mean age 40.4±17.2 years, duration of diabetes 17.2±9.3 years, HbA1c 8.2±1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. Results. Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (±15) above baseline, compared with 9 ms (±19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (±0.21) above baseline during hypoglycaemia, compared with −0.05 nmol/l (±0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. Conclusion/interpretation. QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia. [Diabetologia (2004) 47:312-315]

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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