Introduction: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Currently, treatment primarily involves alleviation of painful symptoms. Animal studies have demonstrated that glucagon-like-peptide-1 (GLP-1) receptors exist on nerves and that GLP-1 agonism (GLP-1A) is neuroprotective in models of type 2 diabetes (T2DM). Nerve excitability is a novel neurophysiological technique that provides information about the axonal ion channel activity underlying peripheral nerve function and may be used to assess the effect of GLP-1A.
Objective: To investigate the effect of GLP-1A treatment on peripheral nerve function in patients with T2DM.
Methods: 80 patients with T2DM either receiving (n=40) or not receiving (n=40) GLP-1A treatment underwent comprehensive clinical screening, neurophysiological studies and functional assessments. Nerve excitability studies were conducted at the median nerve to assess the activity of sodium and potassium ion channels at different regions of the axon. Maximal walking speed was measured using a 6-metre timed walk. Groups were matched for age, sex, BMI, HbA1c%, duration of diabetes, eGFR and neuropathy severity. An additional 10 patients were assessed before commencement of GLP-1A treatment and retested 3 months post-commencement.
Results: Patients receiving GLP-1A treatment demonstrated significant differences in nerve function compared to patients not receiving GLP-1A treatment despite being matched for neuropathy severity and other variables. These differences in ion channel activity were observed in the internodal (P<0.05) and nodal regions (P<0.005) of the axon and suggest healthier nerve function. Patients receiving GLP-1A treatment also exhibited higher maximal walking speeds (P<0.05). Patients that commenced GLP-1A treatment demonstrated a significant improvement in ion channel activity in the internodal region (p<0.05) following treatment.
Conclusion: Significant differences in nerve function were observed with GLP-1A treatment. Based on previous studies 1, these results suggest nerve function may be preserved in patients receiving GLP-1A treatment, which may be beneficial in the prevention and management of DPN in T2DM.