Background

Despite medication, surgery, and diet; type 2 diabetes mellitus (T2DM) remains challenging to effectively treat. We are developing a new therapeutic concept of using vagal neuromodulation which will offer an improved treatment experience for type 2 diabetics: minimizing noncompliance and treatment costs. It involves low frequency stimulation of vagal celiac fibers innervating the pancreas with simultaneous reversible high frequency alternating current conduction block of vagal hepatic fibers innervating the liver. This method has demonstrated increased glycemic control in a Zucker rat model of T2DM as well as in an alloxan treated swine model of T2DM. In swine experiments (n=3) glycemic control was assessed by applying stimulation and block for the duration of six 4-hour oral glucose tolerance tests (OGTTs). The total accumulative time was 24 hours which may lead to beta cell exhaustion. To test for exhaustion blood insulin was measured during an OGTT prior to and following experiments. The insulin response was quantified by calculating the area under the curve (AUC) of insulin versus time (µIU/mL*min=area unit (AU)). First to note, there was an apparent, but non-significant, increase in baseline insulin following stimulation and block experiments. (pre-experiments =10.7±2.6 µIU/mL, post-experiments=15.4±2.9 µIU/mL, p=0.28). In terms of overall response there was no significant change in AUC (pre-experiments =3906±565 AU, post-experiments=5866±698 AU, p=0.09). These results suggest that multiple applications of stimulation of the celiac branch did not cause beta cell exhaustion using our neuromodulation technique and, with further studies, may offer new therapeutic option for T2DM.