impaired glucose tolerance neuropathy, IGTN, impaired glucose tolerance, IGT, diabetic neuropathy, metabolic syndrome
Approximately 40% of persons with idiopathic neuropathy have impaired glucose tolerance-a condition referred to as impaired glucose tolerance neuropathy (IGTN). Two studies presented at the 58th annual meeting of the American Academy of Neurology, held in San Diego from April 1 through April 8, looked at characteristics of IGTN-specifically, the role of exercise and diet in ameliorating nerve damage and the association between the metabolic syndrome and IGTN.The first study, funded by the National Institute of Neurological Disorders and Stroke (NINDS) and conducted by a multi-institutional team, determined that diet and exercise elicit cutaneous reinnervation and ameliorate neuropathic pain. The second study, conducted by a team from the University of Utah, found a high prevalence of the metabolic syndrome among patients who had idiopathic neuropathy and normal glucose tolerance (NGT).To determine whether an exercise and diet regimen could ameliorate pain in patients with IGTN, researchers studied 32 patients over the course of 1 year as they followed a diet and exercise program modeled after the Diabetes Prevention Project, a randomized study funded by the National Institute of Diabetesand Digestive and Kidney Diseases (NIDDK). "The NIDDK study demonstrated that diet and exercise counseling was superior to both placebo and metformin in preventing progression from prediabetes to diabetes," explained principal investigator of the NINDS study J. Robinson Singleton, MD, associate professor, Department of Neurology, University of Utah, Salt Lake City. The NIDDK study was led by one of Singleton's collaborators on the 2 studies reported here: A. Gordon Smith, MD, associate professor, Department of Neurology, University of Utah."The goals of counseling in the NINDS study were a 7% loss in body weight or normalization of body mass index and an increase of moderate aerobic exercise to 150 minutes per week or 30 minutes 5 times weekly," Singleton explained. To determine the intraepidermal nerve fiber density (IENFD), the team performed 3-mm skin biopsies at the distal leg and proximal thigh at baseline and a year after all study participants had been following the diet and exercise plan.By the study's end, the IENFD had increased by about a third for all patients except those with the worst loss of nerve fibers in their extremities. The improvement in proximal IENFD correlated with decreased neuropathic pain and a change in sural sensory amplitude. "Over the first year of follow-up, IGTN subjects lost an average of 4% of their body weight and increased exercise from less than 15 minutes to more than 80 minutes per week," said Singleton.In a press briefing at the AAN meeting, Smith noted that the findings indicate that the effects of IGTN may be reversible. In correspondence with Applied Neurology, Singleton echoed Smith's view, commenting that the findings "are of great clinical significance, because the neurology community regards length-dependent neuropathy in general and diabetic neuropathy in particular as irreversible and progressive. The data underscore the importance of identifying neuropathy patients very early in the course of their disease."In the second study, conducted by Singleton, Smith, and Kristi Rose, a second-year student in the Department of Medicine at the University of Utah, data on 184 persons with peripheral neuropathy were reviewed. Heretofore unrecognized impaired glucose tolerance (IGT) was identified in 87 persons. These patients were compared with persons who had peripheral neuropathy but had NGT and with 57 persons who had early peripheral neuropathy.The researchers found that the metabolic syndrome was much more common among both the neuropathic patients with IGT and NGT compared with prevalence within the general population. The researchers surmised that hypertension and hyperlipidemia may play roles in the pathogenesis of idiopathic peripheral neuropathy or that obesity characterized by hypertension, hyperlipidemia, and hyperglycemia may contribute to its development. "These data suggest that control of glucose alone may not be sufficient, and that concurrent treatment of obesity, hypertension, and hyperlipidemia may also improve neuropathy or reduce its severity," said Singleton.