Antibodies to glutamic acid decarboxylase and peripheral nerve function intype 1 diabetes

Autoimmune mechanisms have been implicated in the pathophysiology of diabet ic neuropathy. We studied the association between glutamic acid decarboxyla se (GAD65) and islet cell (IA-2) autoantibodies as well as autoantibodies t o the autonomic nervous system and peripheral nerve function in recent onse t type 1 diabetes. Thirty-seven patients (27 females and 10 males) enrolled 2-22 months after diagnosis. Humoral factors, glycemic control, and periph eral nerve function were measured annually for 3 yr. Patients with high GAD65Ab had worse glycemic control and higher insulin re quirements. Patients with high GAD65Ab had slower motor nerve conduction ve locities in the median, ulnar, and peroneal nerves (P < 0.025 for each nerv e). The mean motor nerve conduction velocity Z scores at the time of the th ird 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 betwe en the low and high GAD65Ab groups were observed for F wave latencies, ther mal threshold detection, and cardiovascular autonomic function. The composi te 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 patien ts 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 assoc iated with worse glycemic control and slightly worse peripheral nerve funct ion. Although the latter remained within normal limits and none of the pati ents had clinical neuropathy, the GAD65Ab-related differences in composite peripheral nerve function were highly significant (P < 0.001) and could not be attributed to GADB65Ab-related differences in glycemic control.