Diabetes Care, Vol 22, Issue 11 1839-1844, Copyright © 1999 by American Diabetes Association

ARTICLES

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

GL Pittenger, RA Malik, N Burcus, AJ Boulton and AI Vinik
Department of Internal Medicine, Strelitz Diabetes Institutes, Norfolk, Virginia, USA. pittengl@evms.edu

OBJECTIVE: Neuropathy is the most common complication of diabetes, and toxic 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 autonomic nerve fiber damage. Sera were applied to N1E-115 and VSC4.1 neuroblastoma cells in vitro as models of sensory/autonomic (S/A) and motor neurons, respectively. Neurotoxicity was measured as either complete or near-complete cell death (highly toxic), inhibited cell growth (moderately toxic), or normal cell proliferation (nontoxic) compared with pooled human serum controls during culture over 4 days. RESULTS: There was an inverse correlation between neurotoxicity and vibration perception threshold (P < 0.01). Age (P < 0.02), duration of diabetes (P < 0.02), and HbA1c (P < 0.03) correlated with neurotoxicity, suggesting that glycation may contribute to cytotoxicity in this model. S/A neurotoxicity 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 type 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 the 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 neuropathy by acting in concert with hyperglycemia to damage sensory/autonomic neurons.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Granberg, N. Ejskjaer, M. Peakman, and G. Sundkvist Autoantibodies to Autonomic Nerves Associated With Cardiac and Peripheral Autonomic Neuropathy Diabetes Care, August 1, 2005; 28(8): 1959 - 1964. [Abstract] [Full Text] [PDF]

				A. J.M. Boulton, R. A. Malik, J. C. Arezzo, and J. M. Sosenko Diabetic Somatic Neuropathies Diabetes Care, June 1, 2004; 27(6): 1458 - 1486. [Full Text] [PDF]

				A. I. Vinik, R. E. Maser, B. D. Mitchell, and R. Freeman Diabetic Autonomic Neuropathy Diabetes Care, May 1, 2003; 26(5): 1553 - 1579. [Abstract] [Full Text] [PDF]

				K. R. Sharma, J. Cross, O. Farronay, D. R. Ayyar, R. T. Shebert, and W. G. Bradley Demyelinating Neuropathy in Diabetes Mellitus Arch Neurol, May 1, 2002; 59(5): 758 - 765. [Abstract] [Full Text] [PDF]