Pilot: Noninvasive Neuromodulation to Enhance Glucose Homeostasis in Individuals with Spinal Cord Injury and Diabetes

Abstract Spinal cord injury (SCI) significantly increases the risk of type 2 diabetes (T2D) and cardiometabolic disease due to paralysis-induced metabolic dysfunction. Individuals with SCI have more than twice the prevalence of T2D compared to able-bodied populations, while current treatments primarily manage symptoms and often require multi-drug regimens with associated risks. Novel interventions targeting underlying metabolic dysfunction are needed. Transcutaneous spinal cord stimulation (tSCS) is a noninvasive neuromodulation approach that has shown promise in improving autonomic and metabolic function. This pilot study will evaluate the acute and chronic effects of tSCS on glucose metabolism in individuals with chronic SCI and T2D. In Aim 1, participants will undergo randomized oral glucose tolerance tests (OGTTs) with and without tSCS to assess glucose and insulin responses and insulin sensitivity. In Aim 2, participants will complete a 12-week intervention including blind and open-label tSCS phases to examine longer-term metabolic outcomes, including HbA1c. Primary outcomes include OGTT-derived glucose and insulin area under the curve and HbA1c responder rates (≥0.5% reduction). This study will provide preliminary evidence for tSCS as a novel, noninvasive therapy to improve glucose homeostasis in this high-risk population.