title: 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.
authors.affiliation: Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Lee
authors.forename: Lishan
authors.initials: L
authors.lastname: Yeoh
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Harris
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Davies
authors.forename: Robert T
authors.initials: RT
authors.lastname: Robinson
authors.forename: Andrew
authors.initials: A
authors.lastname: Leathard
authors.forename: Christopher
authors.initials: C
authors.lastname: Newman
authors.forename: Ian A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: Simon R
authors.initials: SR
authors.lastname: Heller
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000209:etiology* / Q000503:physiopathology*; D001794:Blood Pressure; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000503:physiopathology*; D004562:Electrocardiography; D004837:Epinephrine / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011188:Potassium / Q000097:blood
chemical_list: D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine