Metabolic Effects of Dual Neuromodulation of Vagus Nerve in a Type 2 Diabetic Model

Background: Despite medication, surgery and diet; type 2 diabetes mellitus (T2DM) remains challenging to effectively treat. Modulation of nerves innervating organs that regulate plasma glucose (PG) may be a novel method for treating T2DM. Standalone stimulation of the vagus nerve or vagotomy/treatments has mixed/ undesirable results. Neuromodulation consisting of stimulation of celiac fibers innervating the pancreas w/ simultaneous reversible electrical blockade of neuronal hepatic fibers innervating the liver is new therapeutic concept that that we have successfully tested in animal models of T2DM. Previously, area under the curve of oral glucose tolerance tests (OGTTs) was calculated to quantify glycemic control. However, fluctuations in glucose during the OGTTs was not accessed. These fluctuations may have importance in treating T2DM in that large fluctuations in PG has been shown to increase oxidative stress and lead to co-morbidities in T2DM. Glucose fluctuations were studied during OGTTs with application of Stim/Block in diabetic swine in the study. Methods: Celaic fibers were stimulated at a frequency of 1 Hz with concurrent application of high frequency alternating current (5000 Hz) blockade to hepatic fibers. Standard deviation (SD) and % coefficient of variation (%CV) were used to quantify glycose variability during the OGTTs in an alloxan treated swine model of type 2 diabetes(n=3 w/ 3 OGTT). Results: It was found that Stim/Block significantly decreased SD and %CV compared to Sham (Sham SD=62±11 mg/dL, Stim/Block SD=13±1 mg/dL (p