Autoimmunity Against Autonomic Nerves Implicated in Diabetic Autonomic...

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Autoimmunity Against Autonomic Nerves Implicated in Diabetic Autonomic

Neuropathy

Laurie Barclay, MD

Aug. 5, 2005 — Autoimmunity against autonomic nerves is associated with

development of cardiac and peripheral autonomic neuropathy in people

with type 1 diabetes, according to the results of a prospective study

reported in the August issue of Diabetes Care.

" Diabetic autonomic neuropathy has been associated with increased

levels of circulating immune complexes and activated T-cells, " write

Viktoria Granberg, MD, from Lund University and Malmö University

Hospital in Sweden, and colleagues. " Moreover, autoantibodies to

autonomic nerve structures (ANabs) have been reported independently

from several different laboratories. Although some of these studies

have implied a correlation between ANabs and autonomic dysfunction,

this has been difficult to establish. "

The investigators prospectively followed up patients with type 1

diabetes and evaluated their autonomic nerve function on four occasions

(at the time of blood sampling, three and six years previously, and

seven years after). At the third examination, 41 patients were tested

for ANabs (complement-fixing autoantibodies to the sympathetic

ganglion, vagus nerve, and adrenal medulla), while cardiac autonomic

nerve function was evaluated with heart rate variation during deep

breathing (expiration-inspiration ratio) and heart-rate reaction to

tilt (acceleration and brake index), and vasoconstriction after

indirect cooling (vasoconstriction index) was evaluated as a measure of

peripheral sympathetic nerve function.

At the third examination, 23 (56%) of 41 patients had ANabs (ANabs+).

Compared with patients without ANabs (ANabs-), ANabs+ patients had

significantly higher frequencies of at least one abnormal cardiac

autonomic nerve function test at the third examination (17 [74%] of 23

vs 7 [39%] of 18; P = .03) and fourth examination (15 [71%] of 21 vs 4

[25%] of 16; P < .01). However, both groups had similar results at the

first and second examination.

The relative risk for ANabs+ patients to develop cardiac autonomic

neuropathy at follow-up was 7.5 (95% confidence interval, 1.72 -

32.80), and the vasoconstriction index at the fourth examination was

more abnormal in ANabs+ than in ANabs- patients (median, 1.40

[interquartile range, 1.58] vs 0.35 [2.05]; P < 0.01).

" ANabs were associated with future development of cardiac and

peripheral autonomic neuropathy in diabetic patients, implying an

etiological relationship between nervous tissue autoimmunity and these

diabetes complications, " the authors write. " The autoimmunity theory

does not preclude the possibility that hyperglycemic and vascular

factors also have a primary role in the development of these

complications. Indeed, we propose a scenario in which autonomic nerve

damage primarily caused by metabolic and/or vascular factors is an

early event, exposing epitopes against which sufficient immunologic

tolerance does not exist, which leads to autonomic nerve infiltration

by activated lymphocytes and the production of ANabs. "

The Swedish Diabetes Association, the Ernhold Lundström Foundation,

Research Funds of Malmö University Hospital, the Swedish Heart-Lung

Foundation, the Albert Påhlsson Foundation, the Segerfalk Foundation,

and the Swedish Medical Research Council supported this study. The

payment of page charges defrayed in part the costs of publication of

this article, which must therefore be marked " advertisement " in

accordance with 18 U.S.C. Section 1734.

Diabetes Care. 2005;28:1959-1964

Reviewed by D. Vogin, MD

http://www.medscape.com/viewarticle/510262