Glutamic acid decarboxylase antibodies, autonomic nerve antibodies and autonomic neuropathy in diabetic patients

Abstract

SummaryTo clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GADab was similar (38 %) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43 %) of patients with and in 27 of 112 (24 %) of patients without sympathetic ganglia antibodies, in 5 of 15 (33 %) of patients with and 31 of 118 (26 %) without adrenal medulla antibodies, and in 5 of 15 (33 % ) with and 31 of 118 (26 %) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48 %] vs 21 of 112 [19 %];p < 0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures. [Diabetologia (1994) 37: 293-299]

Diverging evolution of anti-GAD and anti-IA-2 antibodies in long-standing diabetes mellitus as a function of age at onset: no association with complications

“…We may not have had the power to decide this but our negative results confirm previous reports [11][12][13][14][15] (but one 24 ) of a lack of relationship between GAD-A and either neuropathy or other microvascular complications. They are also in agreement with the data of Muhr 15 and Zerbini 14 who did not find any higher frequency of IA2-A in patients with autonomic cardiac neuropathy or nephropathy, respectively.…”

“…[11][12][13][14] The prevalence of GAD-A and IA2-A after 10 years in this study is higher than that previously observed for classical islet cell antibodies. 12,15,16 This discrepancy is probably due to the greater sensitivity of this assay.…”

Subclinical nerve dysfunction in children and adolescents with IDDM

“…Late age of diabetes onset correlated to nerve dysfunction, but since age of onset correlated strongly to height we believe that increased height explains this finding. As shown earlier both in peripheral somatic [49] and autonomic nerves [50] absence of GAD-ab does not prevent nerve dysfunction.…”

Islet-infiltrating B-Cells in Nonobese Diabetic Mice Predominantly Target Nervous System Elements

“…Nevertheless, since humoral immune responses against autonomous nervous tissue have been described in newly diagnosed type 1 diabetic patients (45)(46)(47)(48) and in genetically predisposed individuals (49,50), it is tempting to speculate that our observations are not a peculiarity of NOD mice. Moreover, an early loss of islet sympathetic nerves during the course of the diabetes has been also observed in BioBreeder diabetic rats (26).…”