Specific fiber deficits in sensorimotor diabetic polyneuropathy correspondto cytotoxicity against neuroblastoma cells of sera from patients with diabetes

OBJECTIVE - Neuropathy is the most common complication of diabetes, and tox ic serum factors may contribute to its genesis. RESEARCH DESIGN AND METHODS - We assessed neurotoxicity in the serum of 39 diabetic patients and correlated it with clinical measures of somatic and a utonomic nerve fiber damage. Sera were applied to N1E-115 and VSC4.1 neurob lastoma cells in vitro as models of sensory/autonomic (S/A) and motor neuro ns, respectively. Neurotoxicity was measured as either complete or near-com plete cell death (highly toxic), inhibited cell growth (moderately toxic), or normal cell proliferation (nontoxic) compared with pooled human serum co ntrols during culture over 4 days. RESULTS - There was an inverse correlation between neurotoxicity and vibrat ion perception threshold (P < 0.01). Age (P < 0.02), duration of diabetes ( P < 0.02), and HbA(1c) (P < 0.03) correlated with neurotoxicity, suggesting that glycation may contribute to cytotoxicity in this model. S/A neurotoxi city occurred more frequently in the sera of patients with type 1 (19 of 25 ) than type 2 (5 of 14) diabetes (P < 0.02). None of the sera from either t ype 1 or type 2 diabetic patients displayed neurotoxicity on VSC4.1 cells, whereas sera from patients with motor neuropathy were highly toxic. CONCLUSIONS - These studies indicate that there is a relationship between t he specific nerve fiber dysfunction in the patient and the type of neuronal cell killed, not only for diabetic neuropathy but also for known forms of autoimmune neuropathies. Such toxic factors may contribute to diabetic neur opathy by acting in concert with hyperglycemia to damage sensory/autonomic neurons.