Peripheral neuropathy (PN) is a common complication of diabetes, prediabetes, and obesity. We know that strict glycemic (blood sugar) control does not treat PN, and new clinical guidelines instead focus on improving metabolic health by modifying metabolic syndrome (MetS) components through diet and exercise, but how these lifestyle modifications improve PN is unknown. In short, there is no effective treatment and still little is understood about the mechanisms that underly this condition.
The NeuroNetwork for Emerging Therapies, led by primary investigators Eva Feldman, M.D., Ph.D., James W. Albers Distinguished University Professor and Russell N. DeJong Professor of Neurology, and Junghuk Hur, Ph.D., M.S., Assistant Professor of Biomedical Sciences at the University of North Dakota, look to change that with a new R01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases.
The grant, entitled, “Metabolic coupling between Schwann cells and axons is functionally distinct from myelination and is disrupted in obesity, prediabetes, and diabetes,” will test the hypothesis that diet and exercise improve PN by normalizing MetS and nerve insulin sensitivity, which will, in turn, normalize peripheral nerve bioenergetics and function. In other words, they will compare exercise, diet, and the combination of both to see which, if any, generates a superior outcome for nerve function.
The grant will look at the actual cell mechanisms when diet and/or exercise result in beneficial effects in peripheral neuropathy to identify therapy (pharmacologic) targets for those patients who are resistant or unable to institute dietary interventions.
“So far the results have been very promising,” explains Rose C. and Nathan L. Milstein Family Emerging Scholar Stephanie Eid, Ph.D., Assistant Professor of Neurology, a project team member. “The data we have been observing has completely supported our hypothesis. If we are successful, we will be on the cusp of developing successful therapies for an awful and debilitating condition.”
Dr. Eid explains that the next step would be to validate the results in different types of diabetes, separate from obesity, and confirm if they are consistent across the progression of metabolic dysfunction. They would also look at human cells to determine if what they have observed in animal models is translated into human findings.