NEUROPATHY ASSOCIATED WITH IMPAIRED GLUCOSE TOLERANCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sensory neuropathy, often with pain, is a common neurologic problem. In developed countries, type 2 diabetes is the most frequent defined cause of sensory neuropathy. In approximately 40% of patients with neuropathy, no cause can be defined (?idiopathic neuropathy?). We and others have shown that 35-50% of patients with otherwise idiopathic neuropathy have impaired glucose tolerance (IGT), compared to 14% of the age matched general population. IGT is defined as a glucose level after a 2 hour oral glucose tolerance test (OGTT) between 140 and 200 mg/dL and a fasting plasma glucose less than 126 mg/dL. Patients with IGT almost uniformly have a painful sensory neuropathy, linking them to the phenotype of early diabetic neuropathy. The Diabetes Control and Complications Trial (DCCT) clearly showed that neuropathy onset and severity correlates with glycemic control in type I diabetes. In the DCCT, aggressive treatment of hyperglycemia prevented or slowed the progression of neuropathy, while the Diabetes Prevention Program (DPP) shows that intensive diet and exercise modification can prevent progression from IGT to diabetes and sets a standard of care for IGT patients. We hypothesize that episodic hyperglycemia contributes to a neuropathy that is clinically indistinguishable from that observed in patients with frank diabetes, and that aggressive treatment to normalize blood glucose levels will be necessary to slow progression of neuropathy in these patients. To test this hypothesis, we propose a prospective controlled trial to determine if treatment with intensive diet and exercise counseling can stabilize or reverse neuropathy in IGT patients