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 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.
Hoeldtke
R D
RD
Department of Medicine, West Virginia University, Morgantown 26506-9159, USA. rhoeldtke@hsc.wvu.edu
Bryner
K D
KD
Hobbs
G R
GR
Horvath
G G
GG
Riggs
J E
JE
Christie
I
I
Ganser
G
G
Marcovina
S M
SM
Lernmark
A
A
D000293:Adolescent; D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology*; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D017933:Peripheral Nervous System / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology; D014636:Valsalva Maneuver
D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006680:HLA Antigens; D007527:Isoenzymes; C401141:glutamate decarboxylase 2