Antibodies to glutamic acid decarboxylase and peripheral nerve function in type 1 diabetes

Autoimmune mechanisms have been implicated in the pathophysiology of diabetic neuropathy. We studied the association between glutamic acid decarboxylase (GAD65) and islet cell (IA-2) autoantibodies as well as autoantibodies to the autonomic nervous system and peripheral nerve function in recent onse...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2000-09, Vol.85 (9), p.3297-3308
Main Authors: HOELDTKE, Robert D, BRYNER, Kimberly D, HOBBS, Gerald R, HORVATH, Gabriella G, RIGGS, Jack E, CHRISTIE, Ian, GANSER, Gary, MARCOVINA, Santica M, LERNMARK, Ake
Format: Article
Language:English
Subjects:
Adolescent
Adult
Associated diseases and complications
Autonomic Nervous System - physiopathology
Biological and medical sciences
Child
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - physiopathology
Diabetes. Impaired glucose tolerance
Electrocardiography
Electrophysiology
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Female
Glutamate Decarboxylase - immunology
Glutamate Decarboxylase - metabolism
Glycated Hemoglobin A - metabolism
Heart Rate - physiology
HLA Antigens - metabolism
Humans
Isoenzymes - immunology
Isoenzymes - metabolism
Male
Medical sciences
Nerve Fibers - physiology
Neurons, Afferent - physiology
Peripheral Nervous System - physiopathology
Respiratory Mechanics - physiology
Valsalva Maneuver
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Summary:Autoimmune mechanisms have been implicated in the pathophysiology of diabetic neuropathy. We studied the association between glutamic acid decarboxylase (GAD65) and islet cell (IA-2) autoantibodies as well as autoantibodies to the autonomic nervous system and peripheral nerve function in recent onset type 1 diabetes. Thirty-seven patients (27 females and 10 males) enrolled 2-22 months after diagnosis. Humoral factors, glycemic control, and peripheral nerve function were measured annually for 3 yr. Patients with high GAD65Ab had worse glycemic control and higher insulin requirements. Patients with high GAD65Ab had slower motor nerve conduction velocities in the median, ulnar, and peroneal nerves (P < 0.025 for each nerve). The mean motor nerve conduction velocity Z scores at the time of the third evaluation was 0.341 +/- 0.25 for the low GAD65Ab patients and -0.600 +/- 0.25 for the high GAD65Ab patients (P < 0.01). Similar differences between the low and high GAD65Ab groups were observed for F wave latencies, thermal threshold detection, and cardiovascular autonomic function. The composite peripheral nerve function Z scores in the low GAD65Ab patients were 0.62 +/- 11, 0.71 +/- 0.19, and 0.21 +/- 0.14 at the first, second, and third evaluations, significantly different from those in the high GAD65Ab patients in whom they were -0.35 +/- 0.15, -0.46 +/- 0.18, and -0.42 +/- 0.16 (P < 0.001). In summary, GAD65Ab in patients with recent onset type 1 diabetes are associated with worse glycemic control and slightly worse peripheral nerve function. Although the latter remained within normal limits and none of the patients had clinical neuropathy, the GAD65Ab-related differences in composite peripheral nerve function were highly significant (P < 0.001) and could not be attributed to GAD65Ab-related differences in glycemic control.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.85.9.3297