QT Variability and Sympathetic Dysinnervation. The mechanism of adverse prognosis attributable to proarrhythmic cardiac sympathetic dysinnervation in patients with type 2 diabetes is incompletely understood. This study sought the association of cardiac sympathetic dysinnervation with temporal instability of ventricular repolarization assessed by beat-to-beat QT interval variability. (123) I-metaiodobenzylguanidine ((123) I-MIBG) scintigraphy was analyzed in 31 type 2 diabetic patients for cardiac sympathetic dysinnervation (4-hour heart-to-mediastinum ratio <1.8) and regional sympathetic integrity and washout rate (from 15-minute (123) I-MIBG uptake). Relative QT variability was defined from a continuous 5-minute ECG in the supine position (n = 31) and standing position (subgroup; n = 15) by the log ratio of absolute QT variability (QT variance divided by the mean QT interval squared) to heart rate (HR) variability (HR variance divided by the mean HR squared). Patients with (n = 16; 52%) versus without cardiac sympathetic dysinnervation demonstrated higher relative QT variability in the supine position (P < 0.001), owing to lower HR variability. However, on standing, absolute QT variability was significantly raised in these patients (P = 0.009) despite similar HR variability in the 2 groups. Correlations of heart-to-mediastinum ratio with standing QT variability (relative [r =-0.63, P = 0.013] and absolute [r =-0.79, P = 0.001]) were superior to corresponding supine measures (relative [r =-0.47, P = 0.008] and absolute [P = NS]). No associations of QT variability with washout rate or regional (123) I-MIBG uptake were identified.Elevated QT variability is associated with cardiac sympathetic dysinnervation in type 2 diabetes and may contribute to adverse prognosis. Moreover, QT variability may be more specific for cardiac sympathetic innervation when measured in the context of sympathetic activation. (J Cardiovasc Electrophysiol, Vol. 24, pp. 305-313, March 2013).