From the Divisions of Endocrinology and Metabolism (M.J.S., T.S.) and
Nuclear Medicine (D.M.R., K.C.A., F.D., E.F., D.M.W., M.S.), Department of
Internal Medicine, University of Michigan, Ann Arbor, Mich, and Diabetes
Research and Treatment Center (M.A.P.), Southern Illinois University School of
Medicine, Springfield, Ill.
Background—Regional cardiac
sympathetic hyperactivity predisposes to malignant arrhythmias
in nondiabetic cardiac disease. Conversely, however, cardiac
sympathetic denervation predicts increased morbidity and mortality in
severe diabetic autonomic neuropathy (DAN). To unite these
divergent observations, we propose that in diabetes regional cardiac
denervation may elsewhere induce regional sympathetic hyperactivity,
which may in turn act as a focus for chemical and electrical
instability. Therefore, the aim of this study was to explore regional
changes in sympathetic neuronal density and tone in diabetic patients
with and without DAN.
Methods and Results—PET using the sympathetic
neurotransmitter analogue 11C-labeled
hydroxyephedrine ([11C]-HED) was used to characterize
left ventricular sympathetic innervation in diabetic
patients by assessing regional disturbances in myocardial
tracer retention and washout. The subject groups comprised 10 diabetic
subjects without DAN, 10 diabetic subjects with mild DAN, 9 diabetic
subjects with severe DAN, and 10 healthy subjects. Abnormalities of
cardiac [11C]-HED retention were detected in 40% of
DAN-free diabetic subjects. In subjects with mild
neuropathy, tracer defects were observed only in the distal
inferior wall of the left ventricle, whereas with more
severe neuropathy, defects extended to involve the distal
and proximal anterolateral and inferior walls. Absolute
[11C]-HED retention was found to be increased by 33%
(P<0.01) in the proximal segments of the severe DAN
subjects compared with the same regions in the DAN-free subjects (30%;
P<0.01 greater than the proximal segments of the mild
DAN subjects). Despite the increased tracer retention, no appreciable
washout of tracer was observed in the proximal segments,
consistent with normal regional tone but increased sympathetic
innervation. Distally, [11C]-HED retention was decreased
in severe DAN by 33% (P<0.01) compared with the
DAN-free diabetic subjects (21%; P<0.05 lower than the
distal segments of the mild DAN subjects).
Conclusions—Diabetes may result in left ventricular
sympathetic dysinnervation with proximal hyperinnervation complicating
distal denervation. This combination could result in potentially
life-threatening myocardial electrical instability and explain the
enhanced cardioprotection from ß-blockade in these subjects.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Cardiac Sympathetic Dysinnervation in Diabetes
Implications for Enhanced Cardiovascular Risk
Key Words: diabetes mellitus • nervous system, autonomic • imaging • ventricles
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