The major objective of this project is to determine whether pancreas transplantation changes the course of diabetic neuropathy. The hypothesis to be tested is that establishment of a constant euglycemic state by a functioning pancreatic graft will halt or prevent progression of the neuropathy. To accomplish this the study will follow the course of the polyneuropathy in type I diabetic patients treated by either pancreas transplantation or tight insulin therapy for 5 years. The spectrum of nerve involvement in each patient will be evaluated, at onset of the study and at selected intervals, by clinical history and examination and by performing quantitative tests of function in several types of large and small diameter motor and sensory nerve fibers of the somatic and autonomic nervous systems. These will include nerve conduction, thermal and mechanical sensation, cardiorespiratory reflexes, sweating activity, and alternate motion rate. Efforts will also be continued to improve existing tests and to devise new, more sensitive methods to quantify neural function. Our long term objectives are: 1) to compare the effects of treatment by pancreas transplantation and strict insulin control on the overall course of the neuropathy, 2) to determine whether the effects differ for the various types of nerve fibers, 3) to differentiate the neuropathic effects of uremia from those of the diabetes itself, and 4) to accomplish these objectives using a combination of established methods and tests that we design to determine function in a variety of nerve fibers.
| Kennedy, W R; Wendelschafer-Crabb, G (1999) Utility of the skin biopsy method in studies of diabetic neuropathy. Electroencephalogr Clin Neurophysiol Suppl 50:553-9 |
| Navarro, X; Sutherland, D E; Kennedy, W R (1997) Long-term effects of pancreatic transplantation on diabetic neuropathy. Ann Neurol 42:727-36 |
| Navarro, X; Verdu, E; Wendelschafer-Crabb, G et al. (1997) Immunohistochemical study of skin reinnervation by regenerative axons. J Comp Neurol 380:164-74 |
| Navarro, X; Kennedy, W R; Aeppli, D et al. (1996) Neuropathy and mortality in diabetes: influence of pancreas transplantation. Muscle Nerve 19:1009-16 |
| Kennedy, W R; Wendelschafer-Crabb, G; Johnson, T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47:1042-8 |
| Kennedy, W R; Wendelschafer-Crabb, G (1996) Utility of skin biopsy in diabetic neuropathy. Semin Neurol 16:163-71 |
| Navarro, X; Verdu, E; Wendelscafer-Crabb, G et al. (1995) Innervation of cutaneous structures in the mouse hind paw: a confocal microscopy immunohistochemical study. J Neurosci Res 41:111-20 |
| Kennedy, W R; Navarro, X; Sutherland, D E (1995) Neuropathy profile of diabetic patients in a pancreas transplantation program. Neurology 45:773-80 |
| Kennedy, W R; Wendelschafer-Crabb, G; Brelje, T C (1994) Innervation and vasculature of human sweat glands: an immunohistochemistry-laser scanning confocal fluorescence microscopy study. J Neurosci 14:6825-33 |
| Kennedy, W R; Wendelschafer-Crabb, G (1993) The innervation of human epidermis. J Neurol Sci 115:184-90 |
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