This is a request for five years of support of a study of diabetic neuropathy, a common complication of a common disease. The work is a continuation and extension of work originally performed as part of a clinical research center grant. It is an ongoing large-scale cross-sectional and longitudinal clinical and epidemiological study of nerve, eye, kidney, and large artery complications in diabetes mellitus in Rochester, MN (patients of primarily Northern European extraction) and in Prairie Island, MN (Mdewakanton Dakota native people). The main objectives are to delineate the frequency, rate of progression, health, work and life outcomes, and predictive risk profiles in various diabetic neuropathies. Major efforts during previous funding periods were directed towards developing diagnostic criteria and quantitative methods for objectively scoring the severity of peripheral nerve disease. Those tools are now available and will be used in the proposed studies. There are four specific aims. The first is to develop and evaluate clinical end points and composite scores for assessing diabetic polyneuropathy, proximal diabetic neuropathy, diabetic truncal radiculopathy, and upper limb mononeuropathies. Normative scales will be developed and changes in these scores with time will be assessed in the different groups of diabetics.
The second aim i s to evaluate the incidence, prevalence, and clinical outcomes associated with specific manifestations of diabetic neuropathy in the cohorts of diabetics maintained by the Mayo Clinic and extend these observations to include a Native American population. Risk profiles will be developed.
The third aim i s to identify risk factors for the various neuropathies and examine whether there are identifiable groups of diabetics who are at elevated risk of peripheral nerve complications.
The fourth aim i s to use the above information to test the following hypotheses: that the various forms of diabetic neuropathy have different pathogenic mechanisms; that in diabetic polyneuropathy hyperglycemia either directly damages Schwann cells or axons or first damages endoneurial microvessels (probably by mechanisms involving altered blood flow and hypoxia); that immune mechanisms are involved in the development of proximal diabetic neuropathy, truncal radiculopathy, and oculomotor neuropathy.
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