Antibodies to Glutamic Acid Decarboxylase and Peripheral Nerve Function in Type 1 Diabetes*

Abstract

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.