PATHOGENESIS OF AUTONOMIC NEUROPATHY IN TYPE I DIABETES

自身免疫在胰岛细胞破坏发展中的作用， 在I型糖尿病中得到证实。 DeCamilli和同事们 最近在罕见的I型糖尿病患者中证实了抗神经元（抗GAD） 与神经僵硬人综合征相关的抗体 最近 我实验室的研究表明补体结合自身抗体 针对肾上腺髓质，交感神经节和迷走神经， I型糖尿病前期和临床上明显的I型糖尿病患者。 我们 也证明了在肾上腺髓质的淋巴细胞浸润， 在疾病早期死亡的I型糖尿病患者， 长期存在的I型糖尿病患者肾上腺髓质纤维化。 试点 研究表明，自身抗体和自主神经之间的相关性 功能障碍 在本提案中，将检验以下假设： 1. I型糖尿病患者抗肾上腺髓质、抗交感神经 神经节和/或单位迷走神经抗体与 心血管自主神经功能障碍和血糖受损的发展 反调节。 这一假设将通过评估葡萄糖反调节作用来检验。 前瞻性研究I型糖尿病患者的心血管自主神经功能 具有和不具有上述自身抗体的糖尿病受试者。 2. 肾上腺髓质、交感神经节和 迷走神经抗原。 糖蛋白和糖脂形式的糖缀合物 （神经节苷脂）已被描述为神经内分泌抗原靶点， 自身免疫性腺体疾病 预计， 肾上腺髓质和交感神经节抗原可显示结构性 与多腺自身免疫性疾病中已经描述的抗原相似， 疾病，并应导致新的自身抗体测定。

A role for autoimmunity in the development of islet cell destruction has been demonstrated in Type I diabetes. DeCamilli and co-workers have recently demonstrated in rare Type I diabetics anti-neuronal (anti-GAD) antibodies associated with the neurologic stiff-man syndrome. Recent studies in my laboratory have demonstrated complement fixing autoantibodies directed against adrenal medulla, sympathetic ganglia, and vagus nerve in pre-type I diabetes and patients with clinically overt Type I diabetes. We have also demonstrated a lymphocytic infiltrate in the adrenal medulla of Type I diabetics who died early in the disease and a duration dependent fibrosis of the adrenal medulla in long standing Type I diabetics. Pilot studies suggest a correlation between autoantibodies and autonomic dysfunction. In the current proposal the following hypotheses will be tested: 1. Type I diabetic subjects anti-adrenal medullary, anti-sympathetic ganglia and/or unit-vagus nerve antibodies are associated with the development of cardiovascular autonomic dysfunction and impaired glucose counter-regulation. This hypothesis will be tested by evaluating glucose counter-regulatory function and cardiovascular autonomic function prospectively in Type I diabetic subjects with and without the autoantibodies noted above. 2. Characterization of the adrenal medullary, sympathetic ganglia, and vagus nerve antigen(s). Glycoconjugates in the form of both glycoproteins and glycolipids (gangliosides) have been described as neuroendocrine antigenic targets in autoimmune glandular illness. It is expected that characterization of the adrenal medullary and sympathetic ganglia antigens may show structural similarity to the antigens already described in polyglandular autoimmune illnesses and should lead to novel autoantibody assays.